Neurotoxicity Research

, Volume 24, Issue 3, pp 407–459

Neurotoxic Saboteurs: Straws that Break the Hippo’s (Hippocampus) Back Drive Cognitive Impairment and Alzheimer’s Disease

Review Article


Late onset Alzheimer’s disease (AD) is the most common cause of progressive cognitive dysfunction and dementia. Despite considerable progress in elucidating the molecular pathology of this disease, we are not yet close to unraveling its etiopathogenesis. The hippocampus is at the epicenter of cognition being associated with learning and memory. A battery of neurotoxic modifiers has been delineated that may unleash deleterious heterogeneous pathologic impacts. Synergistically they target hippocampus causing its neuronal degeneration, gray matter volume atrophy, and progressive cognitive decline. The neurotoxic factors include aging, stress, depression, hypoxia/hypoxemia, hypertension, diabetes, obesity, alcohol abuse, smoking, malnutrition, and polypharmacy—to name a few. Addressing “upstream pathologies” due to these multiple and heterogeneous neurotoxic modifiers vis-a-vis hippocampal dysfunction is of paramount importance. The downstream-generated inflammatory cytokines, mitochondrial dysfunction, oxidative stress, hypoperfusion, excitotoxicity, amyloid beta, and neurofibrillary tangles may then trigger and sustain neurocognitive pathology. The failure of clinical trials in AD is due in part to this complex multifactorial neurotoxic–pathophysiological labyrinth. The key is to employ appropriate preventive and treatment strategies prior to significant hippocampus damage and its dysfunction. Prevention/reversal of the diverse neurotoxic impacts, delineated here, should be an integral part of therapeutic armamentarium, in order to ameliorate hippocampus dysfunction and to enhance memory in aging, mild cognitive impairment, and AD. Throughout, the paper highlights both the challenges presented by the ever present neurotoxic onslaught, and the opportunities to overcome them. Hence, arresting AD pathogenesis is achievable through early intervention. A targeted approach may ameliorate neurocognitive pathology and attenuate memory deterioration.


Alzheimer’s disease Neurotoxic modifiers Hippocampus BDNF Beta amyloid Neurofibrillary tangles 


  1. Abe Y, Toyosawa K (1999) Age-related changes in rat hippocampal theta rhythms: a difference between type 1 and type 2 theta. J Vet Med Sci 61:543–548PubMedGoogle Scholar
  2. Adams MM, Shi L, Linville MC, Forbes ME, Long AB, Bennett C, Newton IG, Carter CS, Sonntag WE, Riddle DR, Shi L, Adams MM, Linville MC, Newton IG, Forbes ME, Long AB, Riddle DR, Brunso-Bechtold JK (2007) Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis. Exp Neurol 206:70–79PubMedGoogle Scholar
  3. Agartz I, Momenan R, Rawlings RR, Kerich MJ, Hommer DW (1999) Hippocampal volume in patients with alcohol dependence. Arch Gen Psychiat 56:356–363PubMedGoogle Scholar
  4. Agius M, Nandra KS (2012) Do atypical antipsychotics promote neurogenesis as a class effect? Psychiatr Danub 24:S191–S193PubMedGoogle Scholar
  5. Ahn HJ, Zamolodchikov D, Cortes-Canteli M, Norris EH, Glickman JF, Strickland S (2010) Alzheimer’s disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci USA 107:21812–21817PubMedGoogle Scholar
  6. Akchiche N, Bossenmeyer-Pourié C, Kerek R, Martin N, Pourié G, Koziel V, Helle D, Alberto JM, Ortiou S, Camadro JM, Léger T, Guéant JL, Daval JL (2012) Homocysteinylation of neuronal proteins contributes to folate deficiency- associated alterations of differentiation, vesicular transport, and plasticity in hippocampal neuronal cells. FASEB J 26:3980–3992PubMedGoogle Scholar
  7. Albrecht A, Çalışkan G, Oitzl MS, Heinemann U, Stork O (2013) Long-lasting increase of corticosterone after fear memory reactivation: anxiolytic effects and network activity modulation in the ventral hippocampus. Neuropsychopharmacology 38:386–394PubMedGoogle Scholar
  8. Alijan-pour J, Abrari K, Bluki TL, Ghorbanian MT, Goudarzi I, Salmani ME, Mirshekar M (2012) Acute ethanol administration affects memory reactivation: a look at the neuronal density and apoptosis in the rat hippocampus. Pharmacol Biochem Behav 102:321–328PubMedGoogle Scholar
  9. Allen JS, Bruss J, Brown CK, Damasio H (2005) Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region. Neurobiol Aging 26:1245–1260PubMedGoogle Scholar
  10. Alonso M, Medina JH, Pozzo-Miller L (2004) ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. Learn Mem 11:172–178PubMedGoogle Scholar
  11. Alpár A, Ueberham U, Brückner MK, Seeger G, Arendt T, Gärtner U (2006) Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice. Brain Res 1099:189–198PubMedGoogle Scholar
  12. Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571–591PubMedGoogle Scholar
  13. Amenta F, Strocchi P, Sabbatini M (1996) Vascular and neuronal hypertensive brain damage: protective effect of treatment with nicardipine. J Hypertens 14:S29–S35Google Scholar
  14. Anacker C, Cattaneo A, Luoni A, Musaelyan K, Zunszain PA, Milanesi E, Rybka J, Berry A, Cirulli F, Thuret S, Price J, Riva MA, Gennarelli M, Pariante CM (2012) Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacology 38(5):872–883. doi:10.1038/npp.2012.253 PubMedGoogle Scholar
  15. Andin U, Passant U, Gustafson L, Englund E (2007) Alzheimer’s disease (AD) with and without white matter pathology: clinical identification of concurrent cardiovascular disorders. Arch Gerontol Geriatr 44:277–286PubMedGoogle Scholar
  16. Anderson ML, Nokia MS, Govindaraju KP, Shors TJ (2012) Moderate drinking? Alcohol consumption significantly decreases neurogenesis in the adult hippocampus. Neuroscience 224:202–209Google Scholar
  17. Andresen J, Shari NI, Bryan RM Jr (2006) Endothelial influences on cerebrovascular tone. Appl Physiol 100:318–327Google Scholar
  18. Anstey KJ, Mack HA, Cherbuin N (2009) Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry 17:542–555PubMedGoogle Scholar
  19. Antier D, Carswell HV, Brosnan MJ, Hamilton CA, Macrae IM, Groves S, Jardine E, Reid JL, Dominiczak AE (2004) Increased levels of superoxide in brains from old female rats. Free Radic Res 38:177–183PubMedGoogle Scholar
  20. Apelt J, Bigl M, Wunderlich P, Schliebs R (2004) Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology. Int J Dev Neurosci 22:475–484PubMedGoogle Scholar
  21. Apostolova LG, Dutton RA, Dinov ID, Hayashi KM, Toga AW, Cummings JL, Thompson PM (2006) Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps. Arch Neurol 63:693–699Google Scholar
  22. Aubrecht TG, Weil ZM, Magalang UJ, Nelson RJ (2013) Dim light at night interacts with intermittent hypoxia to alter cognitive and affective responses. Am J Physiol Regul Integr Comp Physiol. doi:10.1152/ajpregu.00100.2013
  23. Avila R, Bottino CM (2006) Cognitive changes update among elderly with depressive syndrome. Rev Bras Psiquiatr 28:316–320PubMedGoogle Scholar
  24. Avila J, Wandosell F, Hernández F (2010) Role of glycogen synthase kinase-3 in Alzheimer’s disease pathogenesis and glycogen synthase kinase-3 inhibitors. Exp Rev Neurotherap 10:703–710Google Scholar
  25. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, Yirmiya R (2003) Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 13:826–834PubMedGoogle Scholar
  26. Backhaus J, Junghanns K, Born J, Hohaus K, Faasch F, Hohagen F (2006) Impaired declarative memory consolidation during sleep in patients with primary insomnia: Influence of sleep architecture and nocturnal cortisol release. Biol Psychiat 60:1324–1330PubMedGoogle Scholar
  27. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495PubMedGoogle Scholar
  28. Balakrishnan K, Verdile G, Mehta PD, Beilby J, Nolan D, Galvão DA, Newton R, Gandy SE, Martins RN (2005) Plasma Abeta42 correlates positively with increased body fat in healthy individuals. J Alzheimers Dis 8:269–282PubMedGoogle Scholar
  29. Bambico FR, Belzung C (2012) Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis? Curr Top Behav Neurosci 15:243–291. doi:10.1007/7854_2012_234 Google Scholar
  30. Barha CK, Ishrat T, Epp JR, Galea LA, Stein DG (2011) Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. Exp Neurol 231:72–81Google Scholar
  31. Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93:74–104PubMedGoogle Scholar
  32. Barnes CA (1994) Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci 17:13–18 Repeated belowPubMedGoogle Scholar
  33. Barnes CA, McNaughton BL (1980) Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol 309:473–485PubMedGoogle Scholar
  34. Barnes CA, Suster MS, Shen J, McNaughton BL (1997) Multistability of cognitive maps in the hippocampus of old rats. Nature 388:272–275PubMedGoogle Scholar
  35. Barnes CA, Rao G, Houston FP (2000) LTP induction threshold change in old rats at the perforant path—granule cell synapse. Neurobiol Aging 21:613–620PubMedGoogle Scholar
  36. Baron JC, Levasseur M, Mazoyer B, Legault-Demare F, Mauguière F, Pappata S, Jedynak P, Derome P, Cambier J, Tran-Dinh S et al (1999) Thalamo-cortical diaschisis: PET study in humans. J Neurol Neurosurg Psychiatry 55:935–942Google Scholar
  37. Baron JC, Chételat G, Desgranges B, Perchey G, Landeau B, de la Sayette V, Eustache F (2001) In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease. Neuroimage 14:298–309PubMedGoogle Scholar
  38. Barrientos RM, Higgins EA, Biedenkapp JC, Sprunger DB, Wright-Hardesty KJ, Watkins LR, Rudy JW, Maier SF (2006) Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 27:723–732PubMedGoogle Scholar
  39. Barrio JR, Kepe V, Satyamurthy N, Huang SC, Small G (2008) Amyloid and tau imaging, neuronal losses and function in mild cognitive impairment. J Nutr Health Aging 12:61S–65SPubMedGoogle Scholar
  40. Bass JL, Corwin M, Gozal D, Moore C, Nishida H, Parker S, Schonwald A, Wilker RE, Stehle S, Kinane TB (2004) The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence. Pediatrics 114:805–816PubMedGoogle Scholar
  41. Bastrikova N, Gardner GA, Reece JM, Jeromin A, Dudek SM (2008) Synapse elimination accompanies functional plasticity in hippocampal neurons. PNAS 105:3123–3127PubMedGoogle Scholar
  42. Bayer TA, Wirths O (2008) Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment. Genes Brain Behav 7:6–11PubMedGoogle Scholar
  43. Bazan NG, Palacios-Pelaez R, Lukiw WJ (2002) Hypoxia signaling to genes: significance in Alzheimer’s disease. Mol Neurobiol 26:283–298PubMedGoogle Scholar
  44. Beason-Held LL, Moghekar A, Zonderman AB, Kraut MA, Resnick SM (2007) Longitudinal changes in cerebral blood flow in the older hypertensive brain. Stroke 38:1766–1773PubMedGoogle Scholar
  45. Bechara RG, Kelly AM (2013) Exercise improves object recognition memory and induces BDNF expression and cell proliferation in cognitively enriched rats. Behav Brain Res 245:96–100. doi:10.1016/j.bbr.2013.02.018 PubMedGoogle Scholar
  46. Becker JT, Davis SW, Hayashi KM, Meltzer CC, Toga AW, Lopez OL, Thompson PM (2006) Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment. Arch Neurol 63:97–101PubMedGoogle Scholar
  47. Behl C, Widmann M, Trapp T, Holsboer F (1995) 17β-estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun 216:473–482PubMedGoogle Scholar
  48. Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 22(5):536–542. doi:10.1016/j.semcdb.2011.07.002 PubMedGoogle Scholar
  49. Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485:512–516PubMedGoogle Scholar
  50. Bellinger FP, Madamba S, Siggins GR (1993) Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res 628:227–234PubMedGoogle Scholar
  51. Belliveau JW, Rosen BR, Kantor HL, Rzedzian RR, Kennedy DN, McKinstry RC, Vevea JM, Cohen MS, Pykett IL, Brady TJ (1990) Functional cerebral imaging by susceptibility-contrast NMR. Magn Reson Med 14:538–546PubMedGoogle Scholar
  52. Bendor D, Wilson MA (2012) Biasing the content of hippocampal replay during sleep. Nat Neurosci 15:1439–1444PubMedGoogle Scholar
  53. Bennett MR (2011) The prefrontal–limbic network in depression: a core pathology of synapse regression. Prog Neurobiol 93:457–467PubMedGoogle Scholar
  54. Benomar Y, Naour N, Auborg A, Bailleux V, Gertler A, Djiane J, Guerre-Millo M, Taouis M (2006) Insulin and leptin induce Glut4 plasma membrane translocation and glucose uptake in a human neuronal cell line by a PI 3-kinase dependent mechanism. Endocrinology 147:2550–2556PubMedGoogle Scholar
  55. Berg L, McKeel DW Jr, Miller JP, Storandt M, Rubin EH, Morris JC, Baty J, Coats M, Norton J, Goate AM, Price JL, Gearing M, Mirra SS, Saunders AM (1998) Clinicopathologic studies in cognitively healthy aging and Alzheimer’s disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 55:326–335PubMedGoogle Scholar
  56. Beydoun MA, Beydoun HA, Wang Y (2008) Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obesity Rev 9:204–218Google Scholar
  57. Bi M, Ittner A, Ke YD, Götz J, Ittner LM (2011) Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice. PLoS ONE 6:e26860PubMedGoogle Scholar
  58. Billioti de Gage S, Bégaud B, Bazin F, Verdoux H, Dartigues JF, Pérès K, Kurth T, Pariente A (2012) Benzodiazepine use and risk of dementia: prospective population based study. BMJ 345:e6231PubMedGoogle Scholar
  59. Bittner T, Fuhrmann M, Burgold S, Ochs SM, Hoffmann N, Mitteregger G, Kretzschmar H, LaFerla FM, Herms J (2010) Multiple events lead to dendritic spine loss in triple transgenic Alzheimer’s disease mice. PLoS ONE 5:e15477PubMedGoogle Scholar
  60. Bjorntorp P (2001) Do stress reactions cause abdominal obesity and comorbidities? Obes Rev 2:73–86PubMedGoogle Scholar
  61. Bleich S, Bandelow B, Javaheripour K, Müller A, Degner D, Wilhelm J, Havemann-Reinecke U, Sperling W, Rüther E, Kornhuber J (2003) Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism. Neurosci Lett 335:179–182PubMedGoogle Scholar
  62. Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39PubMedGoogle Scholar
  63. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356PubMedGoogle Scholar
  64. Bobinski M, Wegiel J, Wisniewski HM, Tarnawski M, Reisberg B, Mlodzik B, de Leon MJ, Miller DC (1995) Atrophy of hippocampal formation subdivisions correlates with stage and duration of Alzheimer’s disease. Dementia 6:205–210PubMedGoogle Scholar
  65. Bobinski M, Wegiel J, Wisniewski HM, Tarnawski M, Bobinski M, Reisberg B, De Leon MJ, Miller DC (1996) Neurofibrillary pathology—correlation with hippocampal formation atrophy in Alzheimer disease. Neurobiol Aging 17:909–919PubMedGoogle Scholar
  66. Bobinski M, Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de Leon MJ, Miller DC, Wisniewski HM (1997) Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol 56:414–420PubMedGoogle Scholar
  67. Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA (2008) Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 33:320–331PubMedGoogle Scholar
  68. Borroni B, Anchisi D, Paghera B, Vicini B, Kerrouche N, Garibotto V, Terzi A, Vignolo LA, Di Luca M, Giubbini R, Padovani A, Perani D (2006) Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD. Neurobiol Aging 27:24–31PubMedGoogle Scholar
  69. Bouras C, Hof PR, Morrison JH (1993) Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes. Neurosci Lett 153:131–135PubMedGoogle Scholar
  70. Bourgeat P, Chételat G, Villemagne VL, Fripp J, Raniga P, Pike K, Acosta O, Szoeke C, Ourselin S, Ames D, Ellis KA, Martins RN, Masters CL, Rowe CC, Salvado O (2010) Beta-amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia. Neurology 74:121–127PubMedGoogle Scholar
  71. Bozzali M, Padovani A, Caltagirone C, Borroni B (2011) Regional grey matter loss and brain disconnection across Alzheimer disease evolution. Curr Med Chem 18:2452–2458PubMedGoogle Scholar
  72. Bozzao A, Floris R, Baviera ME, Apruzzese A, Simonetti G (2001) Diffusion and perfusion MR imaging in cases of Alzheimer’s disease: correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol 22:1030–1036PubMedGoogle Scholar
  73. Braak H, Braak E, Bohl J (1993) Staging of Alzheimer-related cortical destruction. Eur Neurol 33:403–408PubMedGoogle Scholar
  74. Brady CB, Spiro A 3rd, Gaziano JM (2005) Effects of age and hypertension status on cognition: the Veterans affairs normative aging study. Neuropsychology 19:770–777PubMedGoogle Scholar
  75. Brecht S, Gelderblom M, Srinivasan A, Mielke K, Dityateva G, Herdegen T (2001) Caspase-3 activation and DNA fragmentation in primary hippocampal neurons following glutamate excitotoxicity. Brain Res Mol Brain Res 94:25–34PubMedGoogle Scholar
  76. Brickman AM, Habeck C, Zarahn E, Flynn J, Stern Y (2007) Structural MRI covariance patterns associated with normal aging and neuropsychological functioning. Neurobiol Aging 28:284–295PubMedGoogle Scholar
  77. Britschgi M, Takeda-Uchimura Y, Rockenstein E, Johns H, Masliah E, Wyss-Coray T (2012) Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice. J Neuroinflammation 9:220PubMedGoogle Scholar
  78. Brook RD, Bard RL, Rubenfire M, Ridker PM, Rajagopalan S (2001) Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol 88:1264–1269PubMedGoogle Scholar
  79. Brothers HM, Marchalant Y, Wenk GL (2010) Caffeine attenuates lipopolysaccharide-induced neuroinflammation. Neurosci Lett 480:97–100PubMedGoogle Scholar
  80. Bruijnzeel AW, Bauzo RM, Munikoti V, Rodrick GB, Yamada H, Fornal CA, Ormerod BK, Jacobs BL (2011) Tobacco smoke diminishes neurogenesis and promotes gliogenesis in the dentate gyrus of adolescent rats. Brain Res 1413:32–42PubMedGoogle Scholar
  81. Brunso-Bechtold JK, Linville MC, Sonntag WE (2000) Age-related synaptic changes in sensorimotor cortex of the Brown Norway X fischer 344 rat. Brain Res 872:125–133PubMedGoogle Scholar
  82. Buckley MJ (2005) The role of the perirhinal cortex and hippocampus in learning, memory, and perception. Q J Exp Psychol B 58:246–268PubMedGoogle Scholar
  83. Burén J, Bergström SA, Loh E, Söderström I, Olsson T, Mattsson C (2007) Hippocampal 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression has a diurnal variability that is lost in the obese Zucker rat. Endocrinology 148:2716–2722PubMedGoogle Scholar
  84. Burger C, Lopez MC, Baker HV, Mandel RJ, Muzyczka N (2008) Genome-wide analysis of aging and learning-related genes in the hippocampal dentate gyrus. Neurobiol Learn Mem 89:379–396Google Scholar
  85. Burnett EJ, Davenport AT, Grant KA, Friedman DP (2012) The effects of chronic ethanol self-administration on hippocampal serotonin transporter density in monkeys. Front Psychiat 3:38Google Scholar
  86. Burnouf S, Martire A, Derisbourg M, Laurent C, Belarbi K, Leboucher A, Fernandez-Gomez FJ, Troquier L, Eddarkaoui S, Grosjean ME, Demeyer D, Muhr-Tailleux A, Buisson A, Sergeant N, Hamdane M, Humez S, Popoli P, Buée L, Blum D (2013) NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model. Aging Cell 12:11–23PubMedGoogle Scholar
  87. Businaro R, Ippoliti F, Ricci S, Canitano N, Fuso A (2012) Alzheimer’s disease promotion by obesity: induced mechanisms-molecular links and perspectives. Curr Gerontol Geriatr Res 2012:986823PubMedGoogle Scholar
  88. Caffarra P, Ghetti C, Concari L, Venneri A (2008) Differential patterns of hypoperfusion in subtypes of mild cognitive impairment. Open Neuroimag J 2:20–28PubMedGoogle Scholar
  89. Cahan C, Decker MJ, Arnold JL, Goldwasser E, Strohl KP (1995) Erythropoietin levels with treatment of obstructive sleep apnea. J Appl Physiol 79:1278–1285PubMedGoogle Scholar
  90. Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344PubMedGoogle Scholar
  91. Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161:598–607PubMedGoogle Scholar
  92. Canas PM, Duarte JM, Rodrigues RJ, Kofalvi A, Cunha RA (2009) Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 30:1877–1884PubMedGoogle Scholar
  93. Casas C, Sergeant N, Itier JM, Blanchard V, Wirths O, Kolk N, Vingtdeux V, Steeg E, Ret G, Canton T, Drobecq H, Clark A, Bonici B, Delacourte A, Benavides J, Schmitz C, Tremp G, Bayer TA, Benoit P, Pradier L (2004) Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. Am J Pathol 165:1289–1300PubMedGoogle Scholar
  94. Castrén E, Rantamäki T (2010) The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 70:289–297PubMedGoogle Scholar
  95. Cendes F, Andermann F, Dubeau F, Matthews PM, Arnold DL (1997) Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy. Evidence from proton MR spectroscopic imaging. Neurology 49:1525–1533PubMedGoogle Scholar
  96. Cerbai F, Lana D, Nosi D, Petkova-Kirova P, Zecchi S, Brothers HM, Wenk GL, Giovannini MG (2012) The neuron- astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus. PLoS ONE 7:e45250PubMedGoogle Scholar
  97. Chai SP, Juan CC, Kao PH, Wang DH, Fong JC (2013) Synergistic induction of interleukin-6 expression by endothelin-1 and cyclic AMP in adipocytes. Int J Obes (Lond) 37:197–203Google Scholar
  98. Chapman TR, Barrientos RM, Ahrendsen JT, Maier SF, Patterson SL (2010) Synaptic correlates of increased cognitive vulnerability with aging: peripheral immune challenge and aging interact to disrupt theta-burst late-phase long-term potentiation in hippocampal area CA1. J Neurosci 30:7598–7603PubMedGoogle Scholar
  99. Chawla MK, Barnes CA (2007) Hippocampal granule cells in normal aging: insights from electrophysiological and functional imaging experiments. Prog Brain Res 163:661–678PubMedGoogle Scholar
  100. Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW (2008) Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 22:301–311PubMedGoogle Scholar
  101. Chen LY, Rex CS, Sanaiha Y, Lynch G, Gall CM (2010) Learning induces neurotrophin signaling at hippocampal synapses. Proc Natl Acad Sci USA 107:7030–7035PubMedGoogle Scholar
  102. Cheng LL, Newell K, Mallory AE, Hyman BT, Gonzalez RG (2002) Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology. Magn Reson Imaging 20:527–533PubMedGoogle Scholar
  103. Chennaoui M, Sauvet F, Drogou C, Van Beers P, Langrume C, Guillard M, Gourby B, Bourrilhon C, Florence G, Gomez- Merino D (2011) Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men. Cytokine 56:318–324PubMedGoogle Scholar
  104. Cherbuin N, Sachdev P, Anstey KJ (2012) Higher normal fasting plasma glucose is associated with hippocampal atrophy: the PATH study. Neurology 79:1019–1026PubMedGoogle Scholar
  105. Chiovenda P, Vincentelli GM, Alegiani F (2002) Cognitive impairment in elderly ED patients: need for multidimensional assessment for better management after discharge. Am J Emerg Med 20:332–335PubMedGoogle Scholar
  106. Chip S, Nitsch C, Wellmann S, Kapfhammer JP (2013) Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death. J Cereb Blood Flow Metab 33:508–518PubMedGoogle Scholar
  107. Choi DW (1994) Glutamate receptors and the induction of excitotoxic neuronal death. Prog Brain Res 100:47–51PubMedGoogle Scholar
  108. Chowdhury MH, Nagai A, Bokura H, Nakamura E, Kobayashi S, Yamaguchi S (2011) Age-related changes in white matter lesions, hippocampal atrophy, and cerebral microbleeds in healthy subjects without major cerebrovascular risk factors. J Stroke Cerebrovasc Dis 20:302–309PubMedGoogle Scholar
  109. Ciaramella A, Sanarico N, Bizzoni F, Moro ML, Salani F, Scapigliati G, Spalletta G, Caltagirone C, Bossù P (2009) Amyloid beta peptide promotes differentiation of pro-inflammatory human myeloid dendritic cells. Neurobiol Aging 30(2):210–221PubMedGoogle Scholar
  110. Cippitelli A, Damadzic R, Hamelink C, Brunnquell M, Thorsell A, Heilig M, Eskay RL (2012) Binge-like ethanol consumption increases corticosterone levels and neurodegeneration whereas occupancy of type II glucocorticoid receptors with mifepristone is neuroprotective. Addict Biol. doi:10.1111/j.1369-1600.2012.00451.x
  111. Cleary J, Hittner JM, Semotuk M, Mantyh P, O’Hare E (1995) Beta-amyloid(1–40) effects on behavior and memory. Brain Res 682:69–74PubMedGoogle Scholar
  112. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. Nat Neurosci 8:79–84PubMedGoogle Scholar
  113. Clodfelder-Miller BJ, Zmijewska AA, Johnson GV, Jope RS (2006) Tau is hyperphosphorylated at multiple sites in mouse brain in vivo after streptozotocin-induced insulin deficiency. Diabetes 55:3320–3325PubMedGoogle Scholar
  114. Cohen-Gadol AA, Pan JW, Kim JH, Spencer DD, Hetherington HH (2004) Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and a histopathological analysis. J Neurosurg 101:613–620PubMedGoogle Scholar
  115. Coleman PD, Yao PJ (2003) Synaptic slaughter in Alzheimer’s disease. Neurobiol Aging 24:1023–1027PubMedGoogle Scholar
  116. Comijs HC, Gerritsen L, Penninx BW, Bremmer MA, Deeg DJ, Geerlings MI (2010) The association between serum cortisol and cognitive decline in older persons. Am J Geriatr Psychiatry 18:42–50PubMedGoogle Scholar
  117. Convit A, Wolf OT, Tarshish C, de Leon MJ (2003) Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly. Proc Natl Acad Sci USA 100:2019–2022PubMedGoogle Scholar
  118. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695PubMedGoogle Scholar
  119. Craik FIM, Simon E (1980) New directions in memory and aging: proceedings of the George A. Talland memorial conference, age differences in memory: the roles of attention and depth of processing, pp 95–112. Lawrence Erlbaum Associates, Hillsdale, NJGoogle Scholar
  120. Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K (2006) Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience 137:437–445PubMedGoogle Scholar
  121. Cuadrado-Tejedor M, Ricobaraza A, Frechilla D, Franco R, Pérez-Mediavilla A, Garcia-Osta A (2012) Chronic mild stress accelerates the onset and progression of the Alzheimer’s disease phenotype in Tg2576 mice. J Alzheimers Dis 28:567–578PubMedGoogle Scholar
  122. Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH (2005) Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci 25:9275–9284PubMedGoogle Scholar
  123. Currais A, Prior M, Lo D, Jolivalt C, Schubert D, Maher P (2012) Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice. Aging Cell 11:1017–1026PubMedGoogle Scholar
  124. da Cunha AA, Ferreira AG, Loureiro SO, da Cunha MJ, Schmitz F, Netto CA, Wyse AT (2012a) Chronic hyperhomocysteinemia increases inflammatory markers in hippocampus and serum of rats. Neurochem Res 37:1660–1669PubMedGoogle Scholar
  125. da Cunha AA, Horn AP, Hoppe JB, Grudzinski PB, Loureiro SO, Ferreira AG, da Cunha MJ, Schmitz F, Salbego CG, Wyse AT (2012b) Evidence that AKT and GSK-3β pathway are involved in acute hyperhomocysteinemia. Int J Dev Neurosci 30:369–374PubMedGoogle Scholar
  126. da Rosa DP, Forgiarini LF, Baronio D, Feijó CA, Martinez D, Marroni NP (2012) Simulating sleep apnea by exposure to intermittent hypoxia induces inflammation in the lung and liver. Mediators Inflamm 2012:879419PubMedGoogle Scholar
  127. Dal Forno G, Palermo MT, Donohue JE, Karagiozis H, Zonderman AB, Kawas CH (2005) Depressive symptoms, sex, and risk for Alzheimer’s disease. Ann Neurol 57:381–387PubMedGoogle Scholar
  128. Dalby NO, Mody I (2003) Activation of NMDA receptors in rat dentate gyrus granule cells by spontaneous and evoked transmitter release. J Neurophysiol 90:786–797PubMedGoogle Scholar
  129. Daselaar SM, Fleck MS, Dobbins IG, Madden DJ, Cabeza R (2006) Effects of healthy aging on hippocampal and rhinal memory functions: an event-related fMRI study. Cereb Cortex 16:1771–1782PubMedGoogle Scholar
  130. Daulatzai MA (2010a) Early stages of pathogenesis in memory impairment during normal senescence and Alzheimer’s disease. J Alzheimers Dis 20:355–367PubMedGoogle Scholar
  131. Daulatzai MA (2010b) Conversion of elderly to Alzheimer’s dementia: role of confluence of hypothermia and senescent stigmata—the plausible pathway. J Alzheimers Dis 21:1039–1063PubMedGoogle Scholar
  132. Daulatzai MA (2012a) Memory and cognitive dysfunctions in Alzheimer’s disease are inextricably intertwined with neuroinflammation due to aging, obesity, obstructive sleep apnea, and other upstream risk factors. In: Costa A, Villalba E (eds) Horizons in neuroscience research. Nova Science Publishers Inc., Hauppauge, NY, pp 69–106Google Scholar
  133. Daulatzai MA (2012b) Pathogenesis of cognitive dysfunction in patients with obstructive sleep apnea: a hypothesis with emphasis on the nucleus tractus solitarius. Sleep Disorders 2012: 251096. doi:10.1155/2012/251096
  134. Daulatzai MA (2012c) Neuroinflammation and dysfunctional nucleus tractus solitarius: their role in neuropathogenesis of Alzheimer’s dementia. Neurochem Res 37:846–868PubMedGoogle Scholar
  135. Daulatzai MA (2012d) Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer’s disease. Neurochem Res 37:2627–2658PubMedGoogle Scholar
  136. Daulatzai MA (2013a) Death by a thousand cuts in Alzheimer’s disease: hypoxia: the prodrome. Neurotox Res 24:216–243Google Scholar
  137. Daulatzai MA (2013b) Cognitive decline and Alzheimer’s disease: a central role for hypoxia-Obstructive sleep apnea and related stigmata in elderly. In: Atta Ur Rahman (ed) Frontiers in clinical drug research: Alzheimer’s disorder. Bentham Publishers, Sharjah (in press)Google Scholar
  138. Davidson TL, Monnot A, Neal AU, Martin AA, Horton JJ, Zheng W (2012) The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood–brain barrier integrity differ for diet-induced obese and diet-resistant rats. Physiol Behav 107:26–33PubMedGoogle Scholar
  139. Davies J, Lloyd KR, Jones IK, Barnes A, Pilowsky LS (2003) Changes in regional cerebral blood flow with venlafaxine in the treatment of major depression. Am J Psychiatry 160:374–376PubMedGoogle Scholar
  140. Davis JB, Maher P (1994) Protein kinase C activation inhibits glutamate-induced cytotoxicity in a neuronal cell line. Brain Res 652:169–173PubMedGoogle Scholar
  141. Davis CJ, Harding JW, Wright JW (2003) REM sleep deprivation-induced deficits in the latency-to-peak induction and maintenance of long-term potentiation within the CA1 region of the hippocampus. Brain Res 973:293–297PubMedGoogle Scholar
  142. Dayyat EA, Zhang SX, Wang Y, Cheng ZJ, Gozal D (2012) Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea. BMC Neurosci 13:77PubMedGoogle Scholar
  143. de Assis AM, Rieger DK, Longoni A, Battu C, Raymundi S, da Rocha RF, Andreazza AC, Farina M, Rotta LN, Gottfried C, Gonçalves CA, Moreira JC, Perry ML (2009) High fat and highly thermolyzed fat diets promote insulin resistance and increase DNA damage in rats. Exp Biol Med 234:1296–1304Google Scholar
  144. De Leon MJ, George AE, Golomb J, Tarshish C, Convit A, Kluger A, De Santi S, McRae T, Ferris SH, Reisberg B, Ince C, Rusinek H, Bobinski M, Quinn B, Miller DC, Wisniewski HM (1997) Frequency of hippocampal formation atrophy in normal aging and Alzheimer’s disease. Neurobiol Aging 18:1–11PubMedGoogle Scholar
  145. De Michele M, Panico S, Iannuzzi A, Celentano E, Ciardullo AV, Galasso R, Sacchetti L, Zarrilli F, Bond MG, Rubba P (2002) Association of obesity and central fat distribution with carotid artery wall thickening in middle-aged women. Stroke 33:2923–2928PubMedGoogle Scholar
  146. de Souza AS, Pacheco Lda C, Castro Pda S, Hokoç JN, Rocha MS, do Carmo MD (2008) Brain fatty acid profiles and spatial learning in malnourished rats: effects of nutritional intervention. Nutr Neurosci 11:119–127PubMedGoogle Scholar
  147. DeCarli C (2003) The role of cerebrovascular disease in dementia. Neurologist 9:123–136PubMedGoogle Scholar
  148. Décary A, Rouleau I, Montplaisir J (2000) Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery. Sleep 23:369–381PubMedGoogle Scholar
  149. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464PubMedGoogle Scholar
  150. den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, van Duijn CM, Hofman A, Breteler MM (2004) Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia. Am J Clin Nutr 80:992–997Google Scholar
  151. den Heijer T, Launer LJ, Prins ND, van Dijk EJ, Vermeer SE, Hofman A, Koudstaal PJ, Breteler MM (2005) Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology 64:263–267Google Scholar
  152. den Heijer T, Geerlings MI, Hoebeek FE, Hofman A, Koudstaal PJ, Breteler MM (2006) Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people. Arch Gen Psychiatry 63:57–62Google Scholar
  153. Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nature Rev Neurosci 11:339–350Google Scholar
  154. Dennis NA, Hayes SM, Prince SE, Madden DJ, Huettel SA, Cabeza R (2008) Effects of aging on the neural correlates of successful item and source memory encoding. J Exp Psychol Learn Mem Cogn 34:791–808PubMedGoogle Scholar
  155. Desgranges B, Baron JC, de la Sayette V, Petit-Taboué MC, Benali K, Landeau B, Lechevalier B, Eustache F (1998) The neural substrates of memory systems impairment in Alzheimer’s disease. A PET study of resting brain glucose utilization. Brain 121:611–631PubMedGoogle Scholar
  156. Deupree DL, Bradley J, Turner DA (1993) Age-related alterations in potentiation in the CA1 region in F344 rats. Neurobiol Aging 14(3):249–258PubMedGoogle Scholar
  157. Devanand DP, Brockington CD, Moody BJ, Brown RP, Mayeux R, Endicott J, Sackeim HA (1992) Behavioral syndromes in Alzheimer’s disease. Int Psychogeriatr 4:161–184PubMedGoogle Scholar
  158. Devanand DP, Pradhaban G, Liu X, Khandji A, De Santi S, Segal S, Rusinek H, Pelton GH, Honig LS, Mayeux R, Stern Y, Tabert MH, de Leon MJ (2007) Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology 68:828–836PubMedGoogle Scholar
  159. Di Filippo M, Chiasserini D, Gardoni F, Viviani B, Tozzi A, Giampà C, Costa C, Tantucci M, Zianni E, Boraso M, Siliquini S, de Iure A, Ghiglieri V, Colcelli E, Baker D, Sarchielli P, Fusco FR, Di Luca M, Calabresi P (2013) Effects of central and peripheral inflammation on hippocampal synaptic plasticity. Neurobiol Dis 52:229–236PubMedGoogle Scholar
  160. Di Paola M, Caltagirone C, Fadda L, Sabatini U, Serra L, Carlesimo GA (2008) Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia. Hippocampus 18:719–728PubMedGoogle Scholar
  161. Dieguez DJ Jr, Barea-Rodriguez EJ (2004) Aging impairs the late phase of long-term potentiation at the medial perforant path-CA3 synapse in awake rats. Synapse 52:53–61PubMedGoogle Scholar
  162. Dinel AL, André C, Aubert A, Ferreira G, Layé S, Castanon N (2011) Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome. PLoS ONE 6:e24325PubMedGoogle Scholar
  163. Domínguez-Alonso A, Ramírez-Rodríguez G, Benítez-King G (2012) Melatonin increases dendritogenesis in the hilus of hippocampal organotypic cultures. J Pineal Res 52:427–436PubMedGoogle Scholar
  164. Dong H, Martin MV, Chambers S, Csernansky JG (2007) Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J Comp Neurol 500:311–321PubMedGoogle Scholar
  165. Dotson VM, Beason-Held L, Kraut MA, Resnick SM (2009) Longitudinal study of chronic depressive symptoms and regional cerebral blood flow in older men and women. Int J Geriatr Psychiatry 24:809–819PubMedGoogle Scholar
  166. Douglas RM, Miyasaka N, Takahashi K, Latuszek-Barrantes A, Haddad GG, Hetherington HP (2007) Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus. Am J Physiol Regul Integr Comp Physiol 292:R1254–R1259PubMedGoogle Scholar
  167. Douglas RM, Ryu J, Kanaan A, Del Carmen Rivero M, Dugan LL, Haddad GG, Ali SS (2010) Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. Am J Physiol Cell Physiol 298:C1594–C1602PubMedGoogle Scholar
  168. Du B, Ohmichi M, Takahashi K, Kawagoe J, Ohshima C, Igarashi H, Mori-Abe A, Saitoh M, Ohta T, Ohishi A, Doshida M, Tezuka N, Takahashi T, Kurachi H (2004) Both estrogen and raloxifene protect against beta-amyloid-induced neurotoxicity in estrogen receptor alpha-transfected PC12 cells by activation of telomerase activity via Akt cascade. J Endocrinol 183:605–615PubMedGoogle Scholar
  169. Duarte A, Proenca T, Oliviera C, Santos M, Rego A (2006) Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress. Diabetes 55:2863–2870PubMedGoogle Scholar
  170. Dumont M, Wille E, Stack C, Calingasan NY, Beal MF, Lin MT (2009) Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer’s disease. FASEB J 23:2459–2466PubMedGoogle Scholar
  171. Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939PubMedGoogle Scholar
  172. Eastwood SL, Harrison PJ (2000) Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5:425–432PubMedGoogle Scholar
  173. Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, Hotton G, Cutler D, Fox N, Kennedy A, Rossor M, Brooks DJ (2007) Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 68:501–508PubMedGoogle Scholar
  174. Eisensehr I, Noachtar S (2001) Haematological aspects of obstructive sleep apnoea. Sleep Med Rev 5:207–221PubMedGoogle Scholar
  175. Eker C, Gonul AS (2010) Volumetric MRI studies of the hippocampus in major depressive disorder: meanings of inconsistency and directions for future research. World J Biol Psychiatry 11:19–35PubMedGoogle Scholar
  176. Elgh E, Lindqvist Astot A, Fagerlund M, Eriksson S, Olsson T, Näsman B (2006) Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer’s disease. Biol Psychiatry 59:155–161PubMedGoogle Scholar
  177. Elliott EM, Mattson MP, Vanderklish P, Lynch G, Chang I, Sapolsky RM (1993) Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo. J Neurochem 61:57–67PubMedGoogle Scholar
  178. El-Solh AA, Mador MJ, Sikka P, Dhillon RS, Amsterdam D, Grant BJ (2002) Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest 121:1541–1547PubMedGoogle Scholar
  179. Engleman HM, Kingshott RN, Martin SE, Douglas NJ (2000) Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). Sleep 23:S102–S108PubMedGoogle Scholar
  180. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, Wall A, Ringheim A, Långström B, Nordberg A (2006) Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 129:2856–2866PubMedGoogle Scholar
  181. Eom TH, Lee HS, Jang PS, Kim YH (2012) Valproate-induced panhypogammaglobulinemia. Neurol Sci 34(6):1003–1004. doi:10.1007/s10072-012-1153-3 PubMedGoogle Scholar
  182. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317PubMedGoogle Scholar
  183. Espinosa-Oliva AM, de Pablos RM, Villarán RF, Argüelles S, Venero JL, Machado A, Cano J (2011) Stress is critical for LPS-induced activation of microglia and damage in the rat hippocampus. Neurobiol Aging 32:85–102PubMedGoogle Scholar
  184. Esposito L, Raber J, Kekonius L, Yan F, Yu G-Q, Bien-Ly N, Puoliväli J, Scearce-Levie K, Masliah E, Mucke L (2006) Reduction in mitochondrial superoxide dismutase modulates Alzheimer’s disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J Neurosci 26:5167–5179PubMedGoogle Scholar
  185. Fadel JR, Jolivalt CG, Reagan LP (2013) Food for thought: the role of appetitive peptides in age-related cognitive decline. Ageing Res Rev. doi:10.1016/j.arr.2013.01.009
  186. Farber NB, Rubin EH, Newcomer JW, Kinscherf DA, Miller JP, Morris JC, Olney JW, McKeel DW Jr (2000) Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry 57(12):1165–1173Google Scholar
  187. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743PubMedGoogle Scholar
  188. Feng J, Wu Q, Zhang D, Chen BY (2012) Hippocampal impairments are associated with intermittent hypoxia of obstructive sleep apnea. Chin Med J (Engl) 125:696–701Google Scholar
  189. Ferretti MT, Bruno MA, Ducatenzeiler A, Klein WL, Cuello AC (2012) Intracellular Aβ-oligomers and early inflammation in a model of Alzheimer’s disease. Neurobiol Aging 33:1329–1342PubMedGoogle Scholar
  190. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117PubMedGoogle Scholar
  191. Fink RI, Kolterman OG, Griffin J, Olefsky JM (1983) Mechanisms of insulin resistance in aging. J Clin Invest 71:1523–1535PubMedGoogle Scholar
  192. Fiorentini A, Rosi MC, Grossi C, Luccarini I, Casamenti F (2010) Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice. PLoS ONE 5:e14382PubMedGoogle Scholar
  193. Firat Guven S, Turkkani MH, Ciftci B, Ulukavak Ciftci T, Erdogan Y (2012) The relationship between high-sensitivity C-reactive protein levels and the severity of obstructive sleep apnea. Sleep Breath 16:217–221Google Scholar
  194. Firbank MJ, Wiseman RM, Burton EJ, Saxby BK, O’Brien JT, Ford GA (2007) Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure. J Neurol 254:713–721PubMedGoogle Scholar
  195. Fischer CE, Jiang D, Schweizer TA (2010) Determining the association of medical co-morbidity with subjective and objective cognitive performance in an inner city memory disorders clinic: a retrospective chart review. BMC Geriatr 10:89PubMedGoogle Scholar
  196. Fitzpatrick AL, Kuller LH, Lopez OL, Diehr P, O’Meara ES, Longstreth WT Jr, Luchsinger JA (2009) Midlife and late-life obesity and the risk of dementia: cardiovascular health study. Arch Neurol 66:336–342PubMedGoogle Scholar
  197. Fonnum F (1984) Glutamate: a neurotransmitter in mammalia brain. J Neurochem 42:1–11PubMedGoogle Scholar
  198. Fonzo LS, Golini RS, Delgado SM, Ponce IT, Bonomi MR, Rezza IG, Gimenez MS, Anzulovich AC (2009) Temporal patterns of lipoperoxidation and antioxidant enzymes are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 19:869–880PubMedGoogle Scholar
  199. Forette F, Seux M-L, Staessen J, Thijs L, Birkenhäger WH, Babarskiene M-R, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Fagard R (1998) Prevention of dementia in randomised double-blind placebo-controlled systolic hypertension in Europe (Syst-Eur) trial. Lancet 352:1347–1351PubMedGoogle Scholar
  200. Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF (2011) Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 198:351–356PubMedGoogle Scholar
  201. Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF (2012) Does lithium prevent Alzheimer’s disease? Drugs Aging 29:335–342PubMedGoogle Scholar
  202. Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL (2005) Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 64:1032–1039PubMedGoogle Scholar
  203. Fox NC, Crum WR, Scahill RI, Stevens JM, Janssen JC, Rossor MN (2001) Imaging of onset and progression of Alzheimer’s disease with voxel-compression mapping of serial magnetic resonance images. Lancet 358:201–205PubMedGoogle Scholar
  204. Frisardia V, Solfrizzia V, Seripab D, Capursoc C, Santamatod A, Sancarlob D, Vendemialec G, Pilottob A, Panzab F (2010) Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer’s disease. Ageing Res Rev 9:399–417Google Scholar
  205. Frisoni GB, Testa C, Zorzan A, Sabattoli F, Beltramello A, Soininen H, Laakso MP (2002) Detection of grey matter loss in mild Alzheimer’s disease with voxel based morphometry. J Neurol Neurosurg Psychiatry 73:657–664PubMedGoogle Scholar
  206. Friston KJ, Frith CD, Liddle PF, Frackowiak RS (1993) Functional connectivity: the principal-component analysis of large (PET) data sets. J Cereb Blood Flow Metab 13:5–14PubMedGoogle Scholar
  207. Frodl T, Meisenzahl EM, Zetzsche T, Höhne T, Banac S, Schorr C, Jäger M, Leinsinger G, Bottlender R, Reiser M, Möller HJ (2004) Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up. J Clin Psychiatry 65:492–499PubMedGoogle Scholar
  208. Frodl T, Schule C, Schmitt G, Born C, Baghai T, Zill P, Bottlender R, Rupprecht R, Bondy B, Reiser M, Möller HJ, Meisenzahl EM (2007) Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 64:410–416PubMedGoogle Scholar
  209. Froissard P, Duval D (1994) Cytotoxic effects of glutamic acid on PC12 cells. Neurochem Int 24:485–493PubMedGoogle Scholar
  210. Fuhrer R, Dufouil C, Dartigues JF (2003) Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study. J Am Geriatr Soc 51:1055–1063PubMedGoogle Scholar
  211. Fujishima M, Ibayashi S, Fujii K, Mori S (1995) Cerebral blood flow and brain function in hypertension. Hypertens Res 18:111–117PubMedGoogle Scholar
  212. Fukuda K, Yuzuriha T, Kinukawa N, Murakawa R, Takashima Y, Uchino A, Ibayashi S, Iida M, Yao H, Hirano M (2009) Alcohol intake and quantitative MRI findings among community dwelling Japanese subjects. J Neurol Sci 278:30–34PubMedGoogle Scholar
  213. Fulda S, Schulz H (2001) Cognitive dysfunction in sleep disorders. Sleep Med Rev 5:423–445PubMedGoogle Scholar
  214. Fung SJ, Xi MC, Zhang JH, Sampogna S, Yamuy J, Morales FR, Chase MH (2007) Apnea promotes glutamate-induced excitotoxicity in hippocampal neurons. Brain Res 1179:42–50Google Scholar
  215. Gao L, Zeng XN, Guo HM, Wu XM, Chen HJ, Di RK, Wu Y (2012) Cognitive and neurochemical alterations in hyperhomocysteinemic rat. Neurol Sci 33:39–43PubMedGoogle Scholar
  216. Garrido GE, Furuie SS, Buchpiguel CA, Bottino CM, Almeida OP, Cid CG, Camargo CH, Castro CC, Glabus MF, Busatto GF (2002) Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer’s disease: a combined MRI and SPECT study. J Neurol Neurosurg Psychiatry 73:508–516PubMedGoogle Scholar
  217. Gazzaley AH, Siegel SJ, Kordower JH, Mufson EJ, Morrison JH (1996) Circuit-specific alterations of N-methyl-d-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys. Proc Natl Acad Sci USA 93:3121–3125PubMedGoogle Scholar
  218. Geda YE, Ragossnig M, Roberts LA, Roberts RO, Pankratz VS, Christianson TJ, Mielke MM, Levine JA, Boeve BF, Sochor O, Tangalos EG, Knopman DS, Petersen RC (2013) Caloric intake, aging, and mild cognitive impairment: a population-based study. J Alzheimers Dis 34:501–507PubMedGoogle Scholar
  219. Geinisman Y, de Toledo-Morrell L, Morrell F, Persina IS, Rossi M (1992) Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. Hippocampus 2:437–444PubMedGoogle Scholar
  220. Gentile MT, Poulet R, Di Pardo A, Cifelli G, Maffei A, Vecchione C, Passarelli F, Landolfi A, Carullo P, Lembo G (2009) Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension. Neurobiol Aging 30:222–228PubMedGoogle Scholar
  221. Gerrard JL, Burke SN, McNaughton BL, Barnes CA (2008) Sequence reactivation in the hippocampus is impaired in aged rats. J Neurosci 28:7883–7890PubMedGoogle Scholar
  222. Gerritsen L, Comijs HC, Deeg DJ, Penninx BW, Geerlings MI (2011) Salivary cortisol, APOE-ε4 allele and cognitive decline in a prospective study of older persons. Neurobiol Aging 32:1615–1625PubMedGoogle Scholar
  223. Ghenimi N, Beauvieux MC, Biran M, Pallet V, Higueret P, Gallis JL (2009) Vitamin A deficiency in rats induces anatomic and metabolic changes comparable with those of neurodegenerative disorders. J Nutr 139:696–702PubMedGoogle Scholar
  224. Giannakopoulos P, Hof PR, Kövari E, Vallet PG, Herrmann FR, Bouras C (1996) Distinct patterns of neuronal loss and Alzheimer’s disease lesion distribution in elderly individuals older than 90 years. J Neuropathol Exp Neurol 55:1210–1220PubMedGoogle Scholar
  225. Giannakopoulos P, Hof PR, Michel JP, Guimon J, Bouras C (1997) Cerebral cortex pathology in aging and Alzheimer’s disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts. Brain Res Brain Res Rev 25:217–245PubMedGoogle Scholar
  226. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology 60:1495–1500PubMedGoogle Scholar
  227. Giannakopoulos P, Gold G, Kövari E, von Gunten A, Imhof A, Bouras C, Hof PR (2007) Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 113:1–12PubMedGoogle Scholar
  228. Gili T, Cercignani M, Serra L, Perri R, Giove F, Maraviglia B, Caltagirone C, Bozzali M (2011) Regional brain atrophy and functional disconnection across Alzheimer’s disease evolution. J Neurol Neurosurg Psychiatry 82:58–66PubMedGoogle Scholar
  229. Gladding CM, Raymond LA (2011) Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. Mol Cell Neurosci 48:308–320PubMedGoogle Scholar
  230. Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, Johnson RW (2005) Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. Faseb J 19:1329–1331PubMedGoogle Scholar
  231. Godoy MC, Tarelli R, Ferrari CC, Sarchi MI, Pitossi FJ (2008) Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain 131:1880–1894Google Scholar
  232. Godsil BP, Kiss JP, Spedding M, Jay TM (2013) The hippocampal-prefrontal pathway: the weak link in psychiatric disorders? Eur Neuropsychopharmacol. doi:10.1016/j.euroneuro.2012.10.018
  233. Godukhin O, Savin A, Kalemenev S, Levin S (2002) Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca(2+) channels. Neuropharmacology 42:459–466PubMedGoogle Scholar
  234. Gold SM, Dziobek I, Sweat V, Tirsi A, Rogers K, Bruehl H, Tsui W, Richardson S, Javier E, Convit A (2007) Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia 50:711–719PubMedGoogle Scholar
  235. Goldbart A, Row BW, Kheirandish L, Schurr A, Gozal E, Guo SZ, Payne RS, Cheng Z, Brittian KR, Gozal D (2003) Intermittent hypoxic exposure during light phase induces changes in cAMP response element binding protein activity in the rat CA1 hippocampal region: water maze performance correlates. Neuroscience 122:585–590PubMedGoogle Scholar
  236. Golini RS, Delgado SM, Navigatore Fonzo LS, Ponce IT, Lacoste MG, Anzulovich AC (2012) Daily patterns of clock and cognition-related factors are modified in the hippocampus of vitamin A-deficient rats. Hippocampus 22:1720–1732PubMedGoogle Scholar
  237. Gomez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol 41:17–24PubMedGoogle Scholar
  238. González RG, Fischman AJ, Guimaraes AR, Carr CA, Stern CE, Halpern EF, Growdon JH, Rosen BR (1995) Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18. Am J Neuroradiol 16:1763–1770PubMedGoogle Scholar
  239. Goodyear LJ, Kahn BB (1998) Exercise, glucose transport, and insulin sensitivity. Ann Rev Med 49:235–261PubMedGoogle Scholar
  240. Gorelick PB (2005) William M. Feinberg Lecture: Cognitive vitality and the role of stroke and cardiovascular disease risk factors. Stroke 36:875–879PubMedGoogle Scholar
  241. Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, Young T (2004) APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. Neurology 63:664–668PubMedGoogle Scholar
  242. Gozal D, Daniel JM, Dohanich GP (2001a) Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci 21:2442–2450PubMedGoogle Scholar
  243. Gozal E, Row BW, Schurr A, Gozal D (2001b) Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat. Neurosci Lett 305:197–201PubMedGoogle Scholar
  244. Grady CL, Haxby JV, Horwitz B, Sundaram M, Berg G, Schapiro MB, Friedland RP, Rapoport SI (1988) Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. J Clin Exp Neuropsychol 10:576–596PubMedGoogle Scholar
  245. Gray JD, Milner TA, McEwen BS (2012) Dynamic plasticity: the role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors. Neuroscience 239:214–227. doi:10.1016/j.neuroscience.2012.08.034 Google Scholar
  246. Greenberg DL, Messer DF, Payne ME, Macfall JR, Provenzale JM, Steffens DC, Krishnan RR (2008) Aging, gender, and the elderly adult brain: an examination of analytical strategies. Neurobiol Aging 29:290–302PubMedGoogle Scholar
  247. Greenfield TK, Rogers JD (1999) Who drinks most of the alcohol in the US? The policy implications. J Stud Alcohol 60:78–89PubMedGoogle Scholar
  248. Gresl TA, Colman RJ, Roecker EB, Havighurst TC, Huang Z, Allison DB, Bergman RN, Kemnitz JW (2001) Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 year. Am J Physiol Endocrinol Metab 281:E757–E765PubMedGoogle Scholar
  249. Griffin WST (2013) Neuroinflammatory cytokine signaling and Alzheimer’s disease. N Engl J Med 368:770–771PubMedGoogle Scholar
  250. Grünblatt E, Salkovic-Petrisic M, Osmanovic J, Riederer P, Hoyer S (2007) Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem 101:757–770PubMedGoogle Scholar
  251. Guenzel FM, Wolf OT, Schwabe L (2013) Stress disrupts response memory retrieval. Psychoneuroendocrinology 38:1460–1465Google Scholar
  252. Guerra C, Linde-Zwirble WT, Wunsch H (2012) Risk factors for dementia after critical illness in elderly medicare beneficiaries. Crit Care 16:R233PubMedGoogle Scholar
  253. Guo JL, Lee VM (2011) Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem 286:15317–15331PubMedGoogle Scholar
  254. Guo M, Bryant J, Sultana S, Jones O, Royal W 3rd (2012) Effects of vitamin A deficiency and opioids on parvalbumin + interneurons in the hippocampus of the HIV-1 transgenic rat. Curr HIV Res 10:463–468PubMedGoogle Scholar
  255. Gureviciene I, Gurevicius K, Tanila H (2009) Aging and alpha-synuclein affect synaptic plasticity in the dentate gyrus. J Neural Transm 116:13–22PubMedGoogle Scholar
  256. Gustafson D (2006) Adiposity indices and dementia. Lancet Neurol 5:713–720PubMedGoogle Scholar
  257. Guzman-Marin R, Suntsova N, Bashir T, Nienhuis R, Szymusiak R, McGinty D (2008) Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep 31:167–175PubMedGoogle Scholar
  258. Guzowski JF, McNaughton BL, Barnes CA, Worley PF (1999) Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nat Neurosci 2:1120–1124PubMedGoogle Scholar
  259. Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA (2000) Inhibition of activity- dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci 20:3993–4001PubMedGoogle Scholar
  260. Guzowski JF, Setlow B, Wagner EK, McGaugh JL (2001) Experience-dependent gene expression in the rat hippocampus after spatial learning: a comparison of the immediate-early genes Arc, c-fos, and zif268. J Neurosci 21:5089–5098PubMedGoogle Scholar
  261. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112PubMedGoogle Scholar
  262. Haddad GG, Jiang C (1993) O2 deprivation in the central nervous system: on mechanisms of neuronal response, differential sensitivity and injury. Prog Neurobiol 40:277–318PubMedGoogle Scholar
  263. Hairston IS, Little MT, Scanlon MD, Barakat MT, Palmer TD, Sapolsky RM, Heller HC (2005) Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning. J Neurophysiol 94:4224–4233PubMedGoogle Scholar
  264. Haley AP, Knight-Scott J, Simnad VI, Manning CA (2006) Increased glucose concentration in the hippocampus in early Alzheimer’s disease following oral glucose ingestion. Magn Reson Imaging 24:715–720Google Scholar
  265. Hall J, Gonder-Frederick L, Chewning W, Silviera J, Gold P (1989) Glucose enhancement of performance on memory tests in young and aged humans. Neuropsychologia 27:1129–1138PubMedGoogle Scholar
  266. Hamadate N, Yamaguchi T, Sugawara A, Tsujimatsu A, Izumi T, Yoshida T, Ohmura Y, Yoshioka M (2011) Regulation of cerebral blood flow in the hippocampus by neuronal activation through the perforant path: relationship between hippocampal blood flow and neuronal plasticity. Brain Res 1415:1–7PubMedGoogle Scholar
  267. Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 11:682–696PubMedGoogle Scholar
  268. Hargens TA, Guill SG, Kaleth AS, Nickols-Richardson SM, Miller LE, Zedalis D, Gregg JM, Gwazdauskas F, Herbert WG (2013) Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea. Sleep Breath 17:403–409PubMedGoogle Scholar
  269. Harrington F, Saxby BK, McKeith IG, Wesnes K, Ford GA (2000) Cognitive performance in hypertensive and normotensive older subjects. Hypertension 36:1079–1082PubMedGoogle Scholar
  270. Harwood DG, Kalechstein A, Barker WW, Strauman S, St George-Hyslop P, Iglesias C, Loewenstein D, Duara R (2010) The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer’s disease. Int J Geriatr Psychiatry 25:511–518PubMedGoogle Scholar
  271. Hawley DF, Leasure JL (2012) Region-specific response of the hippocampus to chronic unpredictable stress. Hippocampus 22:1338–1349PubMedGoogle Scholar
  272. Hawley DF, Morch K, Christie BR, Leasure JL (2012) Differential response of hippocampal subregions to stress and learning. PLoS ONE 7:e53126PubMedGoogle Scholar
  273. Hayashi T, Fukuyama H, Katsumi Y, Hanakawa T, Nagahama Y, Yamauchi H, Tsukada H, Shibasaki H (1999) Cerebral glucose metabolism in unilateral entorhinal cortex-lesioned rates: an animal PET study. NeuroReport 10:2113–2118PubMedGoogle Scholar
  274. Hege Nilsen L, Rae C, Ittner LM, Götz J, Sonnewald U (2013) Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation. J Cereb Blood Flow Metab 33:684–691Google Scholar
  275. Hein AM, Stasko MR, Matousek SB, Scott-McKean JJ, Maier SF, Olschowka JA, Costa AC, O’Banion MK (2010) Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav Immun 24:243–253PubMedGoogle Scholar
  276. Heise V, Filippini N, Ebmeier KP, Mackay CE (2011) The APOE ε4 allele modulates brain white matter integrity in healthy adults. Molec Psychiat 16:908–916PubMedGoogle Scholar
  277. Hellstrom IC, Danik M, Luheshi GN, Williams S (2005) Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-beta-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus 15:656–664PubMedGoogle Scholar
  278. Henkel LA, Johnson MK, De Leonardis DM (1998) Aging and source monitoring: cognitive processes and neuropsychological correlates. J Exp Psychol Gen 127:251–268PubMedGoogle Scholar
  279. Hermida AP, McDonald WM, Steenland K, Levey A (2012) The association between late-life depression, mild cognitive impairment and dementia: is inflammation the missing link? Expert Rev Neurother 12:1339–1350PubMedGoogle Scholar
  280. Hickie I, Naismith S, Ward PB, Turner K, Scott E, Mitchell P, Wilhelm K, Parker G (2005) Reduced hippocampal volumes and memory loss in patients with early-and late-onset depression. Br J Psychiatry 186:197–202PubMedGoogle Scholar
  281. Hirota K, Sasaki R, Yamazaki M (2012) Pre-synaptic function explains age-dependent actions of general anesthetics in the rat hippocampal synaptic transmission. Toxicol In Vitro 26:872–877PubMedGoogle Scholar
  282. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397PubMedGoogle Scholar
  283. Ho L, Qin W, Pompl P, Xiang Z, Wang J, Zhao Z, Peng Y, Cambareri G, Rocher A, Mobbs CV, Hof PR, Pasinetti GM (2004) Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. FASEB J 18:902–904PubMedGoogle Scholar
  284. Ho YS, Yang X, Yeung SC, Chiu K, Lau CF, Tsang AW, Mak JC, Chang RC (2012) Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats. PLoS ONE 7:e36752PubMedGoogle Scholar
  285. Hochachka PW, Clark CM, Monge C, Stanley C, Brown WD, Stone CK, Nickles RJ, Holden JE (1996) Sherpa brain glucose metabolism and defense adaptations against chronic hypoxia. J Appl Physiol 81:1355–1361PubMedGoogle Scholar
  286. Hodes GE, Brookshire BR, Hill-Smith TE, Teegarden SL, Berton O, Lucki I (2012) Strain differences in the effects of chronic corticosterone exposure in the hippocampus. Neuroscience 222:269–280PubMedGoogle Scholar
  287. Hof PR (1997) Morphology and neurochemical characteristics of the vulnerable neurons in brain aging and Alzheimer’s disease. Eur Neurol 37:71–81PubMedGoogle Scholar
  288. Hoffman LB, Schmeidler J, Lesser GT, Beeri MS, Purohit DP, Grossman HT, Haroutunian V (2009) Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons. Neurology 72:1720–1726PubMedGoogle Scholar
  289. Holtzman DM, Hyman BT, Spires-Jones TL (2012) Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-β. Brain 135:2155–2168PubMedGoogle Scholar
  290. Hooper C, Killick R, Lovestone S (2008) The GSK3 hypothesis of Alzheimer’s disease. J Neurochem 104:1433–1439PubMedGoogle Scholar
  291. Horwitz B (1994) Data analysis paradigms for metabolic-flow data: combining neural modeling and functional neuroimaging. Hum Brain Mapp 2:112–122Google Scholar
  292. Hoth KF, Tate DF, Poppas A, Forman DE, Gunstad J, Moser DJ, Paul RH, Jefferson AL, Haley AP, Cohen RA (2007) Endothelial function and white matter hyperintensities in older adults with cardiovascular disease. Stroke 38:308–312PubMedGoogle Scholar
  293. Hsieh MH, McQuoid DR, Levy RM, Payne ME, MacFall JR, Steffens DC (2002) Hippocampal volume and antidepressant response in geriatric depression. Int J Geriatr Psychiatry 17:519–525PubMedGoogle Scholar
  294. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, Malinow R (2006) AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss. Neuron 52:831–843PubMedGoogle Scholar
  295. Hua F, Ma J, Ha T, Xia Y, Kelley J, Williams DL, Kao RL, Browder IW, Schweitzer JB, Kalbfleisch JH, Li C (2007) Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. J Neuroimmunol 190:101–111PubMedGoogle Scholar
  296. Huang Y, Wu L, Xu C, Yang B, Wang R (2006) Increased HO-1 expression and decreased iNOS expression in the hippocampus from adult spontaneously hypertensive rats. Cell Biochem Biophys 46:35–42PubMedGoogle Scholar
  297. Hur EM, Zhou FQ (2010) GSK3 signalling in neural development. Nat Rev Neurosci 11:539–551PubMedGoogle Scholar
  298. Hurtado DE, Molina-Porcel L, Carroll JC, Macdonald C, Aboagye AK, Trojanowski JQ, Lee VM (2012) Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer’s disease. J Neurosci 32(21):7392–7402PubMedGoogle Scholar
  299. Huxtable AG, Smith SM, Vinit S, Watters JJ, Mitchell GS (2013) Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia. J Appl Physiol 114:879–887PubMedGoogle Scholar
  300. Irimajiri R, Golob EJ, Starr A (2010) ApoE genotype and abnormal auditory cortical potentials in healthy older females. Neurobiol Aging 31:1799–1804PubMedGoogle Scholar
  301. Irwin MR, Wang M, Ribeiro D, Cho HJ, Olmstead R, Breen EC, Martinez-Maza O, Cole S (2008) Sleep loss activates cellular inflammatory signaling. Biol Psychiatry 64:538–540PubMedGoogle Scholar
  302. Irwin MR, Carrillo C, Olmstead R (2010) Sleep loss activates cellular markers of inflammation: sex differences. Brain Behav Immun 24:54–57PubMedGoogle Scholar
  303. Iseki E, Tsunoda S, Suzuki K, Takayama N, Akatsu H, Yamamoto T, Kosaka K (2002) Regional quantitative analysis of NFT in brains of non-demented elderly persons: comparisons with findings in brains of late-onset Alzheimer’s disease and limbic NFT dementia. Neuropathology 22:34–39PubMedGoogle Scholar
  304. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 142:387–397PubMedGoogle Scholar
  305. Jack CR Jr, Petersen RC, Xu YC, O’Brien PC, Waring SC, Tangalos EG, Smith GE, Ivnik RJ, Thibodeau SN, Kokmen E (1998) Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer’s disease. Ann Neurol 43:303–310PubMedGoogle Scholar
  306. Jack CR Jr, Petersen RC, Xu YC, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Waring SC, Tangalos EG, Kokmen E (1999) Prediction of AD with MRI based hippocampal volume in mild cognitive impairment. Neurology 52:1397–1403PubMedGoogle Scholar
  307. Jack CR Jr, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Tangalos EG, Kokmen E (2000a) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55:484–489PubMedGoogle Scholar
  308. Jack CR Jr, Petersen RC, Farber NB, Rubin EH, Newcomer JW, Kinscherf DA, Miller JP, Morris JC, Olney JW, McKeel DW Jr (2000b) Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry 57:1165–1173Google Scholar
  309. Jack CR Jr, Dickson DW, Parisi JE, Xu YC, Cha RH, O’Brien PC, Edland SD, Smith GE, Boeve BF, Tangalos EG, Kokmen E, Petersen RC (2002) Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology 58:750–757PubMedGoogle Scholar
  310. Jack CR Jr, Shiung MM, Gunter JL, O’Brien PC, Weigand SD, Knopman DS, Boeve BF, Ivnik RJ, Smith GE, Cha RH, Tangalos EG, Petersen RC (2004) Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology 62:591–600PubMedGoogle Scholar
  311. Jack CR Jr, Shiung MM, Weigand SD, O’Brien PC, Gunter JL, Boeve BF, Knopman DS, Smith GE, Ivnik RJ, Tangalos EG, Petersen RC (2005) Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 65:1227–12231PubMedGoogle Scholar
  312. Jacobs DM, Sano M, Dooneief G, Marder K, Bell KL, Stern Y (1995) Neuropsychological detection and characterization of preclinical Alzheimer’s disease. Neurology 45:957–962PubMedGoogle Scholar
  313. Jacobs B, Driscoll L, Schall M (1997) Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J Comp Neurol 386:661–680PubMedGoogle Scholar
  314. Jacobson TK, Howe MD, Schmidt B, Hinman JR, Escabi MA, Markus EJ (2013) Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation. J Neurophysiol 109(7):1852–1865. doi:10.1152/jn.00409.2012 PubMedGoogle Scholar
  315. Jagust WJ, Landau SM (2012) Apolipoprotein E, not fibrillar β-amyloid, reduces cerebral glucose metabolism in normal aging. J Neurosci 32:18227–18233PubMedGoogle Scholar
  316. Janssen J, Hulshoff Pol HE, de Leeuw FE, Schnack HG, Lampe IK, Kok RM, Kahn RS, Heeren TJ (2007) Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. J Neurol Neurosurg Psychiatry 78:638–640PubMedGoogle Scholar
  317. Jefferson AL, Poppas A, Paul RH, Cohen RA (2007) Systemic hypoperfusion is associated with executive dysfunction in geriatric cardiac patients. Neurobiol Aging 28:477–483PubMedGoogle Scholar
  318. Jelic S, Le Jemtel TH (2008) Inflammation, oxidative stress, and the vascular endothelium in obstructive sleep apnea. Trends Cardiovasc Med 18:253–260PubMedGoogle Scholar
  319. Jelic S, Lederer DJ, Adams T, Padeletti M, Colombo PC, Factor PH, Le Jemtel TH (2010) Vascular inflammation in obesity and sleep apnea. Circulation 121:1014–1021PubMedGoogle Scholar
  320. Jennings JM, Jacoby LL (1997) An opposition procedure for detecting age-related deficits in recollection: telling effects of repetition. Psychol Aging 12:352–361PubMedGoogle Scholar
  321. Jernigan TL, Archibald SL, Fennema-Notestine C, Gamst AC, Stout JC, Bonner J, Hesselink JR (2001) Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiol Aging 22:581–594PubMedGoogle Scholar
  322. Jespersen SN, Kroenke CD, Østergaard L, Ackerman JJ, Yablonskiy DA (2007) Modeling dendrite density from magnetic resonance diffusion measurements. Neuroimage 34:1473–1486PubMedGoogle Scholar
  323. Ji L, Nazarali AJ, Paterson PG (2008) Protein-energy malnutrition increases activation of the transcription factor, nuclear factor kappaB, in the gerbil hippocampus following global ischemia. J Nutr Biochem 19:770–777PubMedGoogle Scholar
  324. Jiang WG, Li SX, Liu JF, Sun Y, Zhou SJ, Zhu WL, Shi J, Lu L (2012) Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress. Psychopharmacology (Berl) 227(1):79–92. doi:10.1007/s00213-012-2941-4 Google Scholar
  325. Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101:13363–13367PubMedGoogle Scholar
  326. Jo J, Whitcomb DJ, Olsen KM, Kerrigan TL, Lo S-C, Bru-Mercier G, Dickinson B, Scullion S, Sheng M, Collingridge G, Cho K (2011) Aβ(1–42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β. Nat Neurosci 14:545–547PubMedGoogle Scholar
  327. Jobst KA, Smith AD, Barker CS, Wear A, King EM, Smith A, Anslow PA, Molyneux AJ, Shepstone BJ, Soper N et al (1992) Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 55:190–194PubMedGoogle Scholar
  328. Jope RS, Johnson GVW (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29:95–102PubMedGoogle Scholar
  329. Jung KI, Ju A, Lee HM, Lee SS, Song CH, Won WY, Jeong JS, Hong OK, Kim JH, Kim DJ (2011) Chronic ethanol ingestion, type 2 diabetes mellitus, and brain-derived neurotrophic factor (BDNF) in rats. Neurosci Lett 487:149–152PubMedGoogle Scholar
  330. Kadish I, Thibault O, Blalock EM, Chen KC, Gant JC, Porter NM, Landfield PW (2009) Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment. J Neurosci 29:1805–1816PubMedGoogle Scholar
  331. Kahn MS, Kranjac D, Alonzo CA, Haase JH, Cedillos RO, McLinden KA, Boehm GW, Chumley MJ (2012) Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse. Behav Brain Res 229:176–184PubMedGoogle Scholar
  332. Kamba M, Suto Y, Ohta Y, Inoue Y, Matsuda E (1997) Cerebral metabolism in sleep apnea. Evaluation by magnetic resonance spectroscopy. Am J Respir Crit Care Med 156:296–298PubMedGoogle Scholar
  333. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) APP processing and synaptic function. Neuron 37:925–937PubMedGoogle Scholar
  334. Kandel ER (2001) The molecular biology of memory storage: A dialogue between genes and synapses. Science 294:1030–1038PubMedGoogle Scholar
  335. Kang L, Sebastian BM, Pritchard MT, Pratt BT, Previs SF, Nagy LE (2007) Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines. Alcohol Clin Exp Res 31:1581–1588PubMedGoogle Scholar
  336. Kanoski SE, Davidson TL (2011) Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 103:59–68PubMedGoogle Scholar
  337. Kanoski SE, Meisel RL, Mullins AJ, Davidson TL (2007) The effects of energy-rich diets on discrimination reversal learning and on BDNF in the hippocampus and prefrontal cortex of the rat. Behav Brain Res 182:57–66PubMedGoogle Scholar
  338. Kantarci K, Jack CR Jr (2003) Neuroimaging in Alzheimer disease: an evidence-based review. Neuroimaging Clin N Am 13:197–209PubMedGoogle Scholar
  339. Karbe H, Szelies B, Herholz K, Heiss WD (1990) Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients. J Neurol 237:19–23PubMedGoogle Scholar
  340. Ke YD, Delerue F, Gladbach A, Götz J, Ittner LM (2009) Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer’s disease. PLoS ONE 4:e7917PubMedGoogle Scholar
  341. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223PubMedGoogle Scholar
  342. Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC (2011) Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 68:675–690PubMedGoogle Scholar
  343. Kenna H, Hoeft F, Kelley R, Wroolie T, DeMuth B, Reiss A, Rasgon N (2013) Fasting plasma insulin and the default mode network in women at risk for Alzheimer’s disease. Neurobiol Aging 34:641–649PubMedGoogle Scholar
  344. Kennedy SH, Evans KR, Krüger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158:899–905PubMedGoogle Scholar
  345. Kessler RC (1997) The effects of stressful life events on depression. Annu Rev Psychol 48:191–214PubMedGoogle Scholar
  346. Kim JH, Anwyl R, Suh YH, Djamgoz MB, Rowan MJ (2001) Use-dependent effects of amyloidogenic fragments of β-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo. J Neurosci 21:1327–1333PubMedGoogle Scholar
  347. Kim JB, Ju JY, Kim JH, Kim TY, Yang BH, Lee YS, Son H (2004) Dexamethasone inhibits proliferation of adult hippocampal neurogenesis in vivo and in vitro. Brain Res 1027:1–10PubMedGoogle Scholar
  348. Kim JJ, Lee HJ, Welday AC, Song E, Cho J, Sharp PE, Jung MW, Blair HT (2007) Stress-induced alterations in hippocampal plasticity, place cells, and spatial memory. Proc Natl Acad Sci USA 104:18297–18302PubMedGoogle Scholar
  349. Kim B, Backus C, Oh S, Hayes JM, Feldman EL (2009) Increased Tau phosphorylation and cleavage in mouse models of Type 1 and Type 2 diabetes. Endocrinology 150:5294–5301PubMedGoogle Scholar
  350. Kim E, Grover LM, Bertolotti D, Green TL (2010) Growth hormone rescues hippocampal synaptic function after sleep deprivation. Am J Physiol Regul Integr Comp Physiol 298:R1588–R1596PubMedGoogle Scholar
  351. Kitazawa M, Oddo S, Yamasaki TR, Green KN, LaFerla FM (2005) Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. J Neurosci 25:8843–8853PubMedGoogle Scholar
  352. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62:1556–1560PubMedGoogle Scholar
  353. Klegeris A, McGeer EG, McGeer PL (2007) Therapeutic approaches to inflammation in neurodegenerative disease. Curr Opin Neurol 20:351–357PubMedGoogle Scholar
  354. Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA 93:8455–8459PubMedGoogle Scholar
  355. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergström M, Savitcheva I, Huang GF, Estrada S, Ausén B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Långström B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319PubMedGoogle Scholar
  356. Knutson KL, Ryden AM, Mander BA, Van Cauter E (2006) Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus. Arch Intern Med 166:1768–1774PubMedGoogle Scholar
  357. Kode A, Yang SR, Rahman I (2006) Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells. Respir Res 7:132PubMedGoogle Scholar
  358. Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML, Garcia-Alloza M, Micheva KD, Smith SJ, Kim ML, Lee VM, Hyman BT, Spires-Jones TL (2009) Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci USA 106:4012–4017PubMedGoogle Scholar
  359. Koffie RM, Hyman BT, Spires-Jones TL (2011) Alzheimer’s disease: synapses gone cold. Mol Neurodegener 6:63PubMedGoogle Scholar
  360. Koffie RM, Hashimoto T, Tai HC, Kay KR, Serrano-Pozo A, Joyner D, Hou S, Kopeikina KJ, Frosch MP, Lee VM, Holtzman DM, Hyman BT, Spires-Jones TL (2012) Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-β. Brain 135:2155–2168PubMedGoogle Scholar
  361. Kohjima M, Sun Y, Chan L (2010) Increased food intake leads to obesity and insulin resistance in the tg2576 Alzheimer’s disease mouse model. Endocrinology 151(4):1532–1540PubMedGoogle Scholar
  362. Kohler M, Stradling JR (2010) Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol 7:677–685PubMedGoogle Scholar
  363. Koolschijn NE, van Haren GJ, Lensvelt-Mulders HE, Pol Hulshoff, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30:3719–3735PubMedGoogle Scholar
  364. Kopp C, Longordo F, Nicholson JR, Lüthi A (2006) Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. J Neurosci 26:12456–12465PubMedGoogle Scholar
  365. Korf ES, White LR, Scheltens P, Launer LJ (2004) Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu–Asia aging study. Hypertension 44:29–34PubMedGoogle Scholar
  366. Kramer JH, Mungas D, Reed BR, Wetzel ME, Burnett MM, Miller BL, Weiner MW, Chui HC (2007) Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology 21:412–418PubMedGoogle Scholar
  367. Krieger J (1995) Regulation of plasma volume during obstructive sleep apnoea. J Sleep Res 4:107–111PubMedGoogle Scholar
  368. Kril JJ, Harper CG (2012) Neuroanatomy and neuropathology associated with Korsakoff’s syndrome. Neuropsychol Rev 22:72–80PubMedGoogle Scholar
  369. Kril JJ, Hodges J, Halliday G (2004) Relationship between hippocampal volume and CA1 neuron loss in brains of humans with and without Alzheimer’s disease. Neurosci Lett 361:9–12PubMedGoogle Scholar
  370. Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ (2009) Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323:1211–1215PubMedGoogle Scholar
  371. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033PubMedGoogle Scholar
  372. Kumar A, Thinschmidt JS, Foster TC, King MA (2007) Aging effects on the limits and stability of long-term synaptic potentiation and depression in rat hippocampal area CA1. J Neurophysiol 98:594–601PubMedGoogle Scholar
  373. Lau CG, Zukin RS (2007) NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 8:413–426PubMedGoogle Scholar
  374. Lau CG, Takeuchi K, Rodenas-Ruano A, Takayasu Y, Murphy J, Bennett MVL, Zukin RS (2009) Regulation of NMDA receptor Ca2+ signalling and synaptic plasticity. Biochem Soc Trans 37:1369–1374PubMedGoogle Scholar
  375. Lauderback CM, Kanski J, Hackett JM, Maeda N, Kindy MS, Butterfield DA (2002) Apolipoprotein E modulates Alzheimer’s Abeta(1–42)-induced oxidative damage to synaptosomes in an allele-specific manner. Brain Res 924:90–97PubMedGoogle Scholar
  376. Lavenex P, Amaral DG (2000) Hippocampal–neocortical interaction: a hierarchy of associativity. Hippocampus 10:420–430PubMedGoogle Scholar
  377. Lavie L (2012) Oxidative stress inflammation and endothelial dysfunction in obstructive sleep apnea. Front Biosci 4:1391–1403Google Scholar
  378. Lazarov O, Lee M, Peterson DA, Sisodia SS (2002) Evidence that synaptically released beta-amyloid accumulates as extracellular deposits in the hippocampus of transgenic mice. J Neurosci 22:9785–9793PubMedGoogle Scholar
  379. Leahey TM, Myers TA, Gunstad J, Glickman E, Spitznagel MB, Alexander T, Juvancic-Heltzel J (2007) Abeta40 is associated with cognitive function, body fat and physical fitness in healthy older adults. Nutr Neurosci 10:205–209PubMedGoogle Scholar
  380. Lee CK, Weindruch R, Prolla TA (2000) Gene-expression profile of the ageing brain in mice. Nat Genet 25:294–297PubMedGoogle Scholar
  381. Lee YH, Tharp WG, Maple RL, Nair S, Permana PA, Pratley RE (2008) Amyloid precursor protein expression is upregulated in adipocytes in obesity. Obesity (Silver Spring, Md) 16:1493–1500Google Scholar
  382. Lee H-K, Kumar P, Fu Q, Rosen KM, Querfurth HW (2009a) The insulin/Akt signaling pathway is targeted by intracellular beta-amyloid. Mol Biol Cell 20:1533–1544PubMedGoogle Scholar
  383. Lee YH, Martin JM, Maple RL, Tharp WG, Pratley RE (2009b) Plasma amyloid-beta peptide levels correlate with adipocyte amyloid precursor protein gene expression in obese individuals. Neuroendocrinology 90:383–390PubMedGoogle Scholar
  384. Lee DC, Rizer J, Selenica ML, Reid P, Kraft C, Johnson A, Blair L, Gordon MN, Dickey CA, Morgan D (2010) LPS-induced inflammation exacerbates phospho-tau pathology in rTg4510 mice. J Neuroinflammation 7:56PubMedGoogle Scholar
  385. Lee HY, Tae WS, Yoon HK, Lee BT, Paik JW, Son KR, Oh YW, Lee MS, Ham BJ (2011) Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: An optimized voxel-based morphometry study. J Affect Disord 133(1–2):128–136. doi:10.1016/j.jad.2011.04.006 PubMedGoogle Scholar
  386. Lee CW, Shih YS, Wu SY, Yang T, Lin C, Kuo YM (2012) Hypoglycemia induces tau hyperphosphorylation. Curr Alzheimer Res 10(3):298–308Google Scholar
  387. Lee AM, Kanter BR, Wang D, Lim JP, Zou ME, Qiu C, McMahon T, Dadgar J, Fischbach-Weiss SC, Messing RO (2013) Prkcz null mice show normal learning and memory. Nature 493:416–419PubMedGoogle Scholar
  388. Lehmann M, Ghosh PM, Madison C, Laforce R Jr, Corbetta-Rastelli C, Weiner MW, Greicius MD, Seeley WW, Gorno-Tempini ML, Rosen HJ, Miller BL, Jagust WJ, Rabinovici GD (2013) Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease. Brain 136:844–858PubMedGoogle Scholar
  389. Leibson C, Rocca W, Hanson V, Cha R, Kokmen E, O’Brien P, Palumbo PJ (1997) Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 145:301–308PubMedGoogle Scholar
  390. Levin-Allerhand JA, Lominska CE, Smith JD (2002) Increased amyloid-levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet. J Nutr Health Aging 6:315–319PubMedGoogle Scholar
  391. Leyhe T, Eschweiler GW, Stransky E, Gasser T, Annas P, Basun H, Laske C (2009) Increase of BDNF serum concentration in lithium treated patients with early Alzheimer’s disease. J Alzheimers Dis 16:649–656PubMedGoogle Scholar
  392. Lezoualc’h F, Skutella T, Widmann M, Behl C (1996) Melatonin prevents oxidative stress-induced cell death in hippocampal cells. NeuroReport 7:2071–2077PubMedGoogle Scholar
  393. Li G, Pleasure SJ (2010) Ongoing interplay between the neural network and neurogenesis in the adult hippocampus. Curr Opinion Neurobiol 20:126–133Google Scholar
  394. Li B, Ryder J, Su Y, Zhou Y, Liu F, Ni B (2003) FRAT1 peptide decreases Abeta production in swAPP(751) cells. FEBS Lett 553:347–350PubMedGoogle Scholar
  395. Li F, Calingasan NY, Yu F, Mauck WM, Toidze M, Almeida CG, Takahashi RH, Carlson GA, Beal MF, Lin MT, Gouras GK (2004) Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem 89:1308–1312PubMedGoogle Scholar
  396. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D (2009) Soluble oligomers of amyloid β protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62:788–801PubMedGoogle Scholar
  397. Li X, Han F, Liu D, Shi Y (2010) Changes of Bax, Bcl-2 and apoptosis in hippocampus in the rat model of post-traumatic stress disorder. Neurol Res 32:579–586PubMedGoogle Scholar
  398. Li J, Wang YJ, Zhang M, Fang CQ, Zhou HD (2011) Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer’s disease. Life Sci 89:86–92PubMedGoogle Scholar
  399. Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, Xu B (2012) Dendritically targeted BDNF mRNA is essential for energy balance and response to leptin. Nat Med 18:564–571PubMedGoogle Scholar
  400. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedGoogle Scholar
  401. Lind J, Larsson A, Persson J, Ingvar M, Nilsson LG, Bäckman L, Adolfsson R, Cruts M, Sleegers K, Van Broeckhoven C, Nyberg L (2006) Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory. Neurosci Lett 396:23–27PubMedGoogle Scholar
  402. Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorder. N Engl J Med 330:613–622PubMedGoogle Scholar
  403. Liu F, Pardo LM, Schuur M, Sanchez-Juan P, Isaacs A, Sleegers K, de Koning I, Zorkoltseva IV, Axenovich TI, Witteman JC, Janssens AC, van Swieten JC, Aulchenko YS, Oostra BA, van Duijn CM (2010) The apolipoprotein E gene and its age-specific effects on cognitive function. Neurobiol Aging 31:1831–1833PubMedGoogle Scholar
  404. Liu P, Jing Y, Collie ND, Campbell SA, Zhang H (2011) Pre-aggregated Aβ-(25–35) alters arginine metabolism in the rat hippocampus and prefrontal cortex. Neuroscience 193:269–282PubMedGoogle Scholar
  405. Liu X, Wu Z, Hayashi Y, Nakanishi H (2012a) Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation. Neuroscience 216:133–142PubMedGoogle Scholar
  406. Liu X, Wu Z, Hayashi Y, Nakanishi H (2012b) Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation. Neuroscience 216:133–142PubMedGoogle Scholar
  407. Liu A, Kushida CA, Reaven GM (2013) Risk for obstructive sleep apnea in obese, nondiabetic adults varies with insulin resistance status. Sleep Breath 17:333–338PubMedGoogle Scholar
  408. Lok J, Martin LJ (2002) Rapid subcellular redistribution of Bax precedes caspase-3 and endonuclease activation during excitotoxic neuronal apoptosis in rat brain. J Neurotrauma 19:815–828PubMedGoogle Scholar
  409. Lu W, Göder R (2012) Does abnormal non-rapid eye movement sleep impair declarative memory consolidation? Disturbed thalamic functions in sleep and memory processing. Sleep Med Rev 16:389–394PubMedGoogle Scholar
  410. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci 14:401–416PubMedGoogle Scholar
  411. Luchsinger JA, Tang MX, Shea S, Mayeux R (2004) Hyperinsulinemia and risk of Alzheimer disease. Neurology 63:1187–1192PubMedGoogle Scholar
  412. Lurie A (2011) Endothelial dysfunction in adults with obstructive sleep apnea. Adv Cardiol 46:139–170PubMedGoogle Scholar
  413. Ma T, Hoeffer CA, Wong H, Massaad CA, Zhou P, Iadecola C, Murphy MP, Pautler RG, Klann E (2011) Amyloid β-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide. J Neurosci 31:5589–5595PubMedGoogle Scholar
  414. Ma YQ, Wu DK, Liu JK (2013) mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer’s disease. Mol Med Report 7:623–627Google Scholar
  415. Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, Harper RK, Yan-Go FL, Harper RM (2002) Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med 166:1382–1387PubMedGoogle Scholar
  416. Macey KE, Macey PM, Woo MA, Henderson LA, Frysinger RC, Harper RK, Alger JR, Yan-Go F, Harper RM (2006) Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea. Respir Physiol Neurobiol 151:44–60PubMedGoogle Scholar
  417. MacLullich AM, Ferguson KJ, Deary IJ, Seckl JR, Starr JM, Wardlaw JM (2002) Intracranial capacity and brain volumes are associated with cognition in healthy elderly men. Neurology 59:169–174PubMedGoogle Scholar
  418. MacMaster FP, Kusumakar V (2004) Hippocampal volume in early onset depression. BMC Med 29(2):2Google Scholar
  419. MacQueen G, Frodl T (2011) The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol Psychiatry 16:252–264PubMedGoogle Scholar
  420. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, Nahmias C, Young LT (2003) Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 100:1387–1392PubMedGoogle Scholar
  421. Maestu F, Arrazola J, Fernandez A, Simos PG, Mo C, Gil-Gregorio P, Fernandez S, Papanicolaou A, Ortiz T (2003) Do cognitive patterns of brain magnetic activity correlate with hippocampal atrophy in Alzheimer’s disease? J Neurol Neurosurg Psychiatry 74:208–212PubMedGoogle Scholar
  422. Magariños AM, Li CJ, Gal Toth J, Bath KG, Jing D, Lee FS, McEwen BS (2011) Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons. Hippocampus 21:253–264PubMedGoogle Scholar
  423. Magrané J, Rosen KM, Smith RC, Walsh K, Gouras GK, Querfurth HW (2005) Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J Neurosci 25:10960–10969PubMedGoogle Scholar
  424. Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571PubMedGoogle Scholar
  425. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110PubMedGoogle Scholar
  426. Mamah D, Harms MP, Barch D, Styner M, Lieberman JA, Wang L (2012) Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Front Psychiatry 3:96. doi:10.3389/fpsyt.2012.00096 PubMedGoogle Scholar
  427. Mandelkow EM, Stamer K, Vogel R, Thies E, Mandelkow E (2003) Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging 24:1079–1085PubMedGoogle Scholar
  428. Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, Jagust W, Walker MP (2013) Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci 16:357–364PubMedGoogle Scholar
  429. Manolopoulos KN, Klotz LO, Korsten P, Bornstein SR, Barthel A (2010) Linking Alzheimer’s disease to insulin resistance: the FoxO response to oxidative stress. Mol Psychiatry 15:1046–1052PubMedGoogle Scholar
  430. Marchant NL, Reed BR, Sanossian N, Madison CM, Kriger S, Dhada R, Mack WJ, Decarli C, Weiner MW, Mungas DM, Chui HC, Jagust WJ (2013) The aging brain and cognition: contribution of vascular injury and Aβ to mild cognitive dysfunction. JAMA Neurol 70(4):488–495. doi:10.1001/2013.jamaneurol.405 PubMedGoogle Scholar
  431. Marshall L, Born J (2007) The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 11:442–450PubMedGoogle Scholar
  432. Marsland AL, Gianaros PJ, Abramowitch SM, Manuck SB, Hariri AR (2008) Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiat 64:484–490PubMedGoogle Scholar
  433. Martin M, Rehani K, Jope RS, Michalek SM (2005) Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6:777–784PubMedGoogle Scholar
  434. Martinez A (2008) Preclinical efficacy on GSK-3 inhibitors: towards a future generation of powerful drugs. Med Res Rev 28:773–796PubMedGoogle Scholar
  435. Masi G, Brovedani P (2011) The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression. CNS Drugs 25:913–931PubMedGoogle Scholar
  436. Massaad CA, Washington TM, Pautler RG, Klann E (2009) Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 106:13576–13581Google Scholar
  437. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170PubMedGoogle Scholar
  438. Matté C, Pereira LO, Dos Santos TM, Mackedanz V, Cunha AA, Netto CA, Wyse AT (2009) Acute homocysteine administration impairs memory consolidation on inhibitory avoidance task and decreases hippocampal brain-derived neurotrophic factor immunocontent: prevention by folic acid treatment. Neuroscience 163:1039–1045PubMedGoogle Scholar
  439. Mattson MP (2003) Excitotoxic and excitoprotective mechanisms: abundant targets for the prevention and treatment of neurodegenerative disorders. Neuromolecular Med 3:65–94PubMedGoogle Scholar
  440. Mausbach BT, Ancoli-Israel S, von Känel R, Patterson TL, Aschbacher K, Mills PJ, Ziegler MG, Dimsdale JE, Calleran S, Grant I (2006) Sleep disturbance, norepinephrine, and D-dimer are all related in elderly caregivers of people with Alzheimer disease. Sleep 29:1347–1352PubMedGoogle Scholar
  441. Mayeux R, Small SA (2000) Finding the beginning or predicting the future? Arch Neurol 57:783–784PubMedGoogle Scholar
  442. McArdle N, Hillman D, Beilin L, Watts G (2007) Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Am J Respir Crit Care Med 175:190–195PubMedGoogle Scholar
  443. McCall AL (1992) The impact of diabetes on the CNS (Review). Diabetes 41:557–570PubMedGoogle Scholar
  444. McDermott CM, Hardy MN, Bazan NG, Magee JC (2006) Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus. J Physiol 570:553–565PubMedGoogle Scholar
  445. McDonald M, Dahl E, Overmier J, Mantyh P, Cleary J (1994) Effects of an exogenous beta-amyloid peptide on retention for spatial learning. Behav Neural Biol 62:60–67PubMedGoogle Scholar
  446. McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189PubMedGoogle Scholar
  447. McEwen BS (2006) Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci 8:367–381Google Scholar
  448. McEwen BS, Magarinos AM (2001) Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders. Hum Psychopharmacol 16:S7–S19PubMedGoogle Scholar
  449. McEwen BS, de Leon MJ, Lupien SJ, Meaney MJ (1999) Corticosteroids, the aging brain and cognition. Trends Endocrinol Metab 10:92–96PubMedGoogle Scholar
  450. McGeer PL, McGeer EG (2004) Inflammation and neurodegeneration in Parkinson’s disease. Parkinsonism Relat Disord 10:S3–S7PubMedGoogle Scholar
  451. McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483PubMedGoogle Scholar
  452. McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291PubMedGoogle Scholar
  453. McIntosh AR, Gonzalez-Lima F (1994) Structural equation modeling and its application to network analysis in functional brain imaging. Hum Brain Mapp 2:2–22Google Scholar
  454. McKinnon MC, Yucel K, Nazarov A, MacQueen GM (2009) A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci 34:41–54PubMedGoogle Scholar
  455. McNay EC, Sherwin RS (2004) Effect of recurrent hypoglycemia on spatial cognition and cognitive metabolism in normal and diabetic rats. Diabetes 53:418–425PubMedGoogle Scholar
  456. McNay EC, Williamson A, McCrimmon RJ, Sherwin RS (2006) Cognitive and neural hippocampal effects of long-term moderate recurrent hypoglycemia. Diabetes 55:1088–1095PubMedGoogle Scholar
  457. McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Robert SS (2010a) Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem 93:546–553PubMedGoogle Scholar
  458. McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Sherwin RS (2010b) Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem 93:546–553PubMedGoogle Scholar
  459. McNay EC, Sandusky LA, Pearson-Leary J (2013) Hippocampal insulin microinjection and in vivo microdialysis during spatial memory testing. J Vis Exp 71:e4451. doi:10.3791/4451 PubMedGoogle Scholar
  460. Meerlo P, Mistlberger RE, Jacobs BL, Heller HC, McGinty D (2009) New neurons in the adult brain: the role of sleep and consequences of sleep loss. Sleep Med Rev 13:187–194PubMedGoogle Scholar
  461. Mega MS, Chen SS, Thompson PM, Woods RP, Karaca TJ, Tiwari A, Vinters HV, Small GW, Toga AW (1997) Mapping histology to metabolism: coregistration of stained whole-brain sections to premortem PET in Alzheimer’s disease. NeuroImage 5:147–153PubMedGoogle Scholar
  462. Meguro K, Blaizot X, Kondoh Y, Le Mestric C, Baron JC, Chavoix C (1999) Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer’s disease. Brain 122:1519–1531PubMedGoogle Scholar
  463. Méndez P, Pazienti A, Szabó G, Bacci A (2012) Direct alteration of a specific inhibitory circuit of the hippocampus by antidepressants. J Neurosci 32:16616–16628PubMedGoogle Scholar
  464. Meyer JS, Rauch GM, Rauch RA, Haque A, Crawford K (2000) Cardiovascular and other risk factors for Alzheimer’s disease and vascular dementia. Ann N Y Acad Sci 903:411–423PubMedGoogle Scholar
  465. Mielke R, Schroder R, Fink GR, Kessler J, Herholz K, Heiss WD (1996) Regional cerebral glucose metabolism and postmortem pathology in Alzheimer’s disease. Acta Neuropathol 91:174–179PubMedGoogle Scholar
  466. Millien I, Blaizot X, Giffard C, Mézenge F, Insausti R, Baron JC, Chavoix C (2002) Brain glucose hypometabolism after perirhinal lesions in baboons: implications for Alzheimer disease and aging. J Cereb Blood Flow Metab 22:1248–1261PubMedGoogle Scholar
  467. Min JA, Lee HR, Kim JI, Ju A, Kim DJ, Kaang BK (2011) Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats. Neurosci Lett 500:52–56PubMedGoogle Scholar
  468. Mizutani T, Kashara M (1995) Degeneration of the intrahippocampal routes of the perforant and alvear pathways in senile dementia of Alzheimer type. Neurosci Lett 184:141–144PubMedGoogle Scholar
  469. Mocanu MM, Nissen A, Eckermann K, Khlistunova I, Biernat J, Drexler D, Petrova O, Schönig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2008) The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J Neurosci 28:737–748PubMedGoogle Scholar
  470. Moechars D, Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, Tesseur I, Spittaels K, Haute CV, Checler F, Godaux E, Cordell B, Leuven F (1999) Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 274:6483–6492PubMedGoogle Scholar
  471. Mondragón-Rodríguez S, Trillaud-Doppia E, Dudilot A, Bourgeois C, Lauzon M, Leclerc N, Boehm J (2012) Interaction of endogenous tau protein with synaptic proteins is regulated by N-methyl-d-aspartate receptor-dependent tau phosphorylation. J Biol Chem 287:32040–32053PubMedGoogle Scholar
  472. Morales-Garcia JA, Luna-Medina R, Alonso-Gil S, Sanz-Sancristobal M, Palomo V, Gil C, Santos A, Martinez A, Perez- Castillo A (2012) Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo. ACS Chem Neurosci 3:963–971PubMedGoogle Scholar
  473. Moreno H, Wu WE, Lee T, Brickman A, Mayeux R, Brown TR, Small SA (2007) Imaging the abeta-related neurotoxicity of Alzheimer disease. Arch Neurol 64:1467–1477PubMedGoogle Scholar
  474. Moreno-Gonzalez I, Estrada LD, Sanchez-Mejias E, Soto C (2013) Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease. Nature Communications 4:1495. doi:10.1038/ncomms2494 PubMedGoogle Scholar
  475. Mori S, Kato M, Fujishima M (1995) Impaired maze learning and cerebral glucose utilization in aged hypertensive rats. Hypertension 25:545–553PubMedGoogle Scholar
  476. Morioka M, Kawano T, Yano S, Kai Y, Tsuiki H, Yoshinaga Y, Matsumoto J, Maeda T, Hamada J, Yamamoto H, Fukunaga K, Kuratsu J (2006) Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia. Biochem Biophys Res Commun 347:273–278PubMedGoogle Scholar
  477. Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, Koeppe RA, Mathis CA, Weiner MW, Jagust WJ (2009) Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 132:1310–1323PubMedGoogle Scholar
  478. Morrell MJ, McRobbie DW, Quest RA, Cummin AR, Ghiassi R, Corfield DR (2003) Changes in brain morphology associated with obstructive sleep apnea. Sleep Med 4:451–454PubMedGoogle Scholar
  479. Morys J, Sadowski M, Barcikowska M, Maciejewska B, Narkiewicz O (1994) The second layer neurones of the entorhinal cortex and the perforant path in physiological ageing and Alzheimer’s disease. Acta Neurobiol Exp 54:47–53Google Scholar
  480. Most EI, Aboudan S, Scheltens P, Van Someren EJ (2012) Discrepancy between subjective and objective sleep disturbances in early- and moderate-stage Alzheimer disease. Am J Geriatr Psychiatry 20:460–467PubMedGoogle Scholar
  481. Mota SI, Ferreira IL, Pereira C, Oliveira CR, Rego AC (2012) Amyloid-beta peptide 1–42 causes microtubule deregulation through N-methyl-d-aspartate receptors in mature hippocampal cultures. Curr Alzheimer Res 9(7):844–856PubMedGoogle Scholar
  482. Mu Q, Xie J, Wen Z, Weng Y, Shuyun ZA (1999) Quantitative MR study of the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle in healthy subjects 40 to 90 years of age. AJNR Am J Neuroradiol 20:207–211PubMedGoogle Scholar
  483. Mueller AD, Pollock MS, Lieblich SE, Epp JR, Galea LA, Mistlberger RE (2008a) Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones. Am J Physiol Regul Integr Comp Physiol 294:R1693–R1703PubMedGoogle Scholar
  484. Mueller SG, Schuff N, Raptentsetsang S, Elman J, Weiner MW (2008b) Selective effect of Apo e4 on CA3 and dentate in normal aging and Alzheimer’s disease using high resolution MRI at 4 T. Neuroimage 42:42–48PubMedGoogle Scholar
  485. Mueller AD, Mear RJ, Mistlberger RE (2011) Inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression. Neuroscience 193:170–181PubMedGoogle Scholar
  486. Munch G, Schinzel R, Loske C, Wong A, Durany N, Li JJ, Vlassara H, Smith MA, Perry G, Riederer P (1998) Alzheimer’s disease-synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm 105:439–461PubMedGoogle Scholar
  487. Mungas D, Harvey D, Reed BR, Jagust WJ, DeCarli C, Beckett L, Mack WJ, Kramer JH, Weiner MW, Schuff N, Chui HC (2005) Longitudinal volumetric MRI change and rate of cognitive decline. Neurology 65:565–571PubMedGoogle Scholar
  488. Mustroph ML, King MA, Klein RL, Ramirez JJ (2012) Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats. Behav Brain Res 233:141–148PubMedGoogle Scholar
  489. Nair D, Zhang SX, Ramesh V, Hakim F, Kaushal N, Wang Y, Gozal D (2011) Sleep fragmentation induces cognitive deficits via nicotinamide adenine dinucleotide phosphate oxidase-dependent pathways in mouse. Am J Respir Crit Care Med 184:1305–1312PubMedGoogle Scholar
  490. Narayan SK, Firbank MJ, Saxby BK, Stansby G, Hansrani M, O’Brien JT, Ford GA (2011) Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension. Dement Geriatr Cogn Disord 31:341–348PubMedGoogle Scholar
  491. Nelson TE, Ur CL, Gruol DL (1999) Chronic intermittent ethanol exposure alters CA1 synaptic transmission in rat hippocampal slices. Neuroscience 94:431–442PubMedGoogle Scholar
  492. Nelson TE, Ur CL, Gruol DL (2005) Chronic intermittent ethanol exposure enhances NMDA-receptor-mediated synaptic responses and NMDA receptor expression in hippocampal CA1 region. Brain Res 1048:69–79PubMedGoogle Scholar
  493. Neves G, Cooke SF, Bliss TVP (2008) Synaptic plasticity, memory, and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 9:65–75PubMedGoogle Scholar
  494. Newman MC, Kaszniak AW (2000) Spatial memory and aging: performance on a human analog of the Morris water maze. Aging Neuropsychol Cognit 7:86–93Google Scholar
  495. Nichols LM, Masdeu JC, Mattay VS, Kohn P, Emery M, Sambataro F, Kolachana B, Elvevåg B, Kippenhan S, Weinberger DR, Berman KF (2012) Interactive effect of apolipoprotein e genotype and age on hippocampal activation during memory processing in healthy adults. Arch Gen Psychiatry 69:804–813PubMedGoogle Scholar
  496. Nicotera P, Ankarcrona M, Bonfoco E, Orrenius S, Lipton SA (1997) Neuronal necrosis and apoptosis: two distinct events induced by exposure to glutamate or oxidative stress. Adv Neurol 72:95–101PubMedGoogle Scholar
  497. Nishijima T, Okamoto M, Matsui T, Kita I, Soya H (2012) Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise. J Appl Physiol 112:197–203PubMedGoogle Scholar
  498. Niu W, Qi Y, Qian Y, Gao P, Zhu D (2009) The relationship between apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls. Hypertens Res 32:1060–1066PubMedGoogle Scholar
  499. Niwa K, Carlson GA, Iadecola C (2000) Exogenous A beta1-40 reproduces cerebrovascular alterations resulting from amyloid precursor protein overexpression in mice. J Cereb Blood Flow Metab 20:1659–1668PubMedGoogle Scholar
  500. Nural-Guvener HF, Mutlu N, Gaballa MA (2013) BACE1 levels are elevated in congestive heart failure. Neurosci Lett 532:7–11PubMedGoogle Scholar
  501. O’Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST (2003) Vascular cognitive impairment. Lancet Neurol 2:89–98PubMedGoogle Scholar
  502. O’Brien JT, Lloyd A, McKeith I, Gholkar A, Ferrier N (2004) A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry 161:2081–2090PubMedGoogle Scholar
  503. Ohga E, Nagase T, Tomita T, Teramoto S, Matsuse T, Katayama H, Ouchi Y (1999) Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome. J Appl Physiol 87:10–14Google Scholar
  504. Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y (2003) Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1. J Appl Physiol 94:179–184PubMedGoogle Scholar
  505. Okusaga O, Stewart MCW, Butcher I, Deary I, Fowkes FGR, Price JF (2013) Smoking, hypercholesterolaemia and hypertension as risk factors for cognitive impairment in older adults. Age Ageing 42:306–311PubMedGoogle Scholar
  506. Olopade CO, Mensah E, Gupta R, Huo D, Picchietti DL, Gratton E, Michalos A (2007) Noninvasive determination of brain tissue oxygenation during sleep in obstructive sleep apnea: a near-infrared spectroscopic approach. Sleep 30:1747–1755PubMedGoogle Scholar
  507. O’Reilly JP, Jiang C, Haddad GG (1995) Major differences in response to graded hypoxia between hypoglossal and neocortical neurons. Brain Res 683:179–186PubMedGoogle Scholar
  508. Ormerod BK, Hanft SJ, Asokan A, Haditsch U, Lee SW, Palmer TD (2013) PPARγ activation prevents impairments in spatial memory and neurogenesis following transient illness. Brain Behav Immun 29:28–38PubMedGoogle Scholar
  509. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14:561–566PubMedGoogle Scholar
  510. Ozsoy S, Durak AC, Esel E (2013) Hippocampal volumes and cognitive functions in adult alcoholic patients with adolescent-onset. Alcohol Alcohol 47:9–14Google Scholar
  511. Pace-Schott EF, Spencer RM (2011) Age-related changes in the cognitive function of sleep. Prog Brain Res 191:75–89PubMedGoogle Scholar
  512. Pacheco-Quinto J, Rodriguez de Turco EB, DeRosa S, Howard A, Cruz-Sanchez F, Sambamurti K, Refolo L, Petanceska S, Pappolla MA (2006) Hyperhomocysteinemic Alzheimer’s mouse model of amyloidosis shows increased brain amyloid beta peptide levels. Neurobiol Dis 22:651–656PubMedGoogle Scholar
  513. Palombo V, Scurti R, Muscari A, Puddu GM, Di Iorio A, Zito M, Abate G (1997) Blood pressure and intellectual function in elderly subjects. Age Ageing 26:91–98PubMedGoogle Scholar
  514. Parachikovaa A, Nichola KE, Cotmana CW (2008) Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition. Neurobiol Dis 30:121–129Google Scholar
  515. Parameshwaran K, Sims C, Kanju P, Vaithianathan T, Shonesy BC, Dhanasekaran M, Bahr BA, Suppiramaniam V (2007) Amyloid beta-peptide Abeta(1–42) but not Abeta(1–40) attenuates synaptic AMPA receptor function. Synapse 61:367–374PubMedGoogle Scholar
  516. Parameshwaran K, Dhanasekaran M, Suppiramaniam V (2008) Amyloid beta peptides and glutamatergic synaptic dysregulation. Exp Neurol 210:7–13PubMedGoogle Scholar
  517. Paul RH, Gunstad J, Poppas A, Tate DF, Foreman D, Brickman AM, Jefferson AL, Hoth K, Cohen RA (2005) Neuroimaging and cardiac correlates of cognitive function among patients with cardiac disease. Cerebrovasc Dis 20:129–133PubMedGoogle Scholar
  518. Pavlik V, Massman P, Barber R, Doody R (2013) Differences in the association of peripheral insulin and cognitive function in non-diabetic Alzheimer’s disease cases and normal controls. J Alzheimers Dis 34:449–456PubMedGoogle Scholar
  519. Pawlak R, Skrzypiec A, Sulkowski S, Buczko W (2002) Ethanol-induced neurotoxicity is counterbalanced by increased cell proliferation in mouse dentate gyrus. Neurosci Lett 327:83–86PubMedGoogle Scholar
  520. Pearson-Leary J, McNay EC (2012) Intrahippocampal administration of amyloid-β(1–42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism. J Alzheimers Dis 30:413–422PubMedGoogle Scholar
  521. Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu–Asia aging study. Diabetes 51(4):1256–1262PubMedGoogle Scholar
  522. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D, Saule E, Bouschet T, Matthews P, Isaac JT, Bortolotto ZA, Wang YT, Collingridge GL (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53:703–717PubMedGoogle Scholar
  523. Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, Wang YT, Collingridge GL (2008) The role of GSK-3 in synaptic plasticity. Br J Pharmacol 153:S428–S437PubMedGoogle Scholar
  524. Penner MR, Roth TL, Chawla MK, Hoang LT, Roth ED, Lubin FD, Sweatt JD, Worley PF, Barnes CA (2010) Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 32(12):2198–2210. doi:10.1016/j.neurobiolaging.2010.01.009 PubMedGoogle Scholar
  525. Penniello M-J, Lambert J, Eustache F, Petit-Taboué MC, Barré L, Viader F, Morin P, Lechevalier B, Baron JC (1995) A PET of the functional neuroanatomy of writing impairment in Alzheimer’s disease: the role of the left supramarginal and left angular gyri. Brain 118:697–706PubMedGoogle Scholar
  526. Perea G, Araque A (2007) Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317:1083–1086PubMedGoogle Scholar
  527. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 104:5638–5643PubMedGoogle Scholar
  528. Perera TD, Coplan JD, Lisanby SH, Lipira CM, Arif M, Carpio C, Spitzer G, Santarelli L, Scharf B, Hen R, Rosoklija G, Sackeim HA, Dwork AJ (2007) Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 27:4894–4901PubMedGoogle Scholar
  529. Perlaki G, Orsi G, Kovacs N, Schwarcz A, Pap Z, Kalmar Z, Plozer E, Csatho A, Gabriel R, Komoly S, Janszky I, Janszky J (2011) Coffee consumption may influence hippocampal volume in young women. Brain Imaging Behav 5:274–284PubMedGoogle Scholar
  530. Persson J, Pudas S, Lind J, Kauppi K, Nilsson LG, Nyberg L (2012) Longitudinal structure-function correlates in elderly reveal MTL dysfunction with cognitive decline. Cereb Cortex 22:2297–2304PubMedGoogle Scholar
  531. Pessoa L (2008) On the relationship between emotion and cognition. Nat Rev Neurosci 9:148–158PubMedGoogle Scholar
  532. Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, Nelson J, Davis DG, Hardman J, Foley DJ, Launer LJ (2000) Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu–Asia aging study. Neurobiol Aging 21(1):57–62PubMedGoogle Scholar
  533. Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879–886PubMedGoogle Scholar
  534. Pham E, Crews L, Ubhi K, Hansen L, Adame A, Cartier A, Salmon D, Galasko D, Michael S, Savas JN, Yates JR, Glabe C, Masliah E (2010) Progressive accumulation of amyloid-beta oligomers in Alzheimer’s disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. FEBS J 277:3051–3067PubMedGoogle Scholar
  535. Phiel CJ, Wilson CA, Lee VM-Y, Klein PS (2003) GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 423:435–439PubMedGoogle Scholar
  536. Pickering M, O’Connor JJ (2007) Pro-inflammatory cytokines and their effects in the dentate gyrus. Prog Brain Res 163:339–354PubMedGoogle Scholar
  537. Pietranera L, Saravia F, Gonzalez Deniselle MC, Roig P, Lima A, De Nicola AF (2006) Abnormalities of the hippocampus are similar in deoxycorticosterone acetate-salt hypertensive rats and spontaneously hypertensive rats. J Neuroendocrinol 18:466–474PubMedGoogle Scholar
  538. Pietranera L, Lima A, Roig P, De Nicola AF (2010) Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats. J Neuroendocrinol 22:1082–1092PubMedGoogle Scholar
  539. Pievani M, Galluzzi S, Thompson PM, Rasser PE, Bonetti M, Frisoni GB (2011) APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer’s disease. Neuroimage 55:909–919PubMedGoogle Scholar
  540. Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, Mathis CA, Klunk WE, Masters CL, Rowe CC (2007) Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 130:2837–2844PubMedGoogle Scholar
  541. Pillai A, Terry AV Jr, Mahadik SP (2006) Differential effects of long-term treatment with typical and atypical antipsychotics on NGF and BDNF levels in rat striatum and hippocampus. Schizophr Res 82:95–106PubMedGoogle Scholar
  542. Planel E, Tatebayashi Y, Miyasaka T, Liu L, Wang L, Herman M, Yu WH, Luchsinger JA, Wadzinski B, Duff KE, Takashima A (2007) Insulin dysfunction induces in vivo Tau hyperphosphorylation through distinct mechanisms. J Neurosci 27:13635–13648PubMedGoogle Scholar
  543. Pozzo-Miller L (2006) BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons. Brain Res 1104:45–54PubMedGoogle Scholar
  544. Praticò D (2008) Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 29:609–615PubMedGoogle Scholar
  545. Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21:4183–4187PubMedGoogle Scholar
  546. Price BH, Gurvit H, Weintraub S, Geula C, Leimkuhler E, Mesulam M (1993) Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer’s disease. Arch Neurol 50:931–937PubMedGoogle Scholar
  547. Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC (2001) Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol 58:1395–1402PubMedGoogle Scholar
  548. Profenno LA, Faraone SV (2008) Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer’s disease population. Am J Med Genet B Neuropsychiatr Genet 147B:822–829PubMedGoogle Scholar
  549. Profenno LA, Porsteinsson AP, Faraone SV (2010) Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiat 67:505–512PubMedGoogle Scholar
  550. Prosser-Loose EJ, Verge VM, Cayabyab FS, Paterson PG (2010) Protein-energy malnutrition alters hippocampal plasticity-associated protein expression following global ischemia in the gerbil. Curr Neurovasc Res 7:341–360PubMedGoogle Scholar
  551. Puig KL, Floden AM, Adhikari R, Golovko MY, Combs CK (2012) Amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity. PLoS ONE 7:e30378PubMedGoogle Scholar
  552. Puoliväli J, Wang J, Heikkinen T, Heikkilä M, Tapiola T, van Groen T, Tanila H (2002) Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice. Neurobiol Dis 9:339–347PubMedGoogle Scholar
  553. Qin L, Crews FT (2012) NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration. J Neuroinflammation 9:5PubMedGoogle Scholar
  554. Qin L, He J, Hanes RN, Pluzarev O, Hong JS, Crews FT (2008) Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment. J Neuroinflammation 5:10PubMedGoogle Scholar
  555. Qiu C, Winblad B, Fratiglioni L (2005) The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 4:487–499PubMedGoogle Scholar
  556. Qu X, Xu C, Wang H, Xu J, Liu W, Wang Y, Jia X, Xie Z, Xu Z, Ji C, Wu A, Yue Y (2013) Hippocampal glutamate level and glutamate aspartate transporter (GLAST) are Up-regulated in senior rat associated with isoflurane-induced spatial learning/memory impairment. Neurochem Res 38:59–73PubMedGoogle Scholar
  557. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344PubMedGoogle Scholar
  558. Quiroz-Baez R, Flores-Domínguez D, Arias C (2013) Synaptic aging is associated with mitochondrial dysfunction, reduced antioxidant contents and increased vulnerability to amyloid-β toxicity. Curr Alzheimer Res 10:324–331PubMedGoogle Scholar
  559. Rabinovici GD, Jagust WJ (2009) Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav Neurol 21:117–128PubMedGoogle Scholar
  560. Raivio N, Tiraboschi E, Saarikoski ST, Castrén E, Kiianmaa K (2012) Brain-derived neurotrophic factor expression after acute administration of ethanol. Eur J Pharmacol 687:9–13PubMedGoogle Scholar
  561. Rajala MW, Scherer PE (2003) Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765–3773PubMedGoogle Scholar
  562. Ramirez SH, Fan S, Zhang M, Papugani A, Reichenbach N, Dykstra H, Mercer AJ, Tuma RF, Persidsky Y (2010) Inhibition of glycogen synthase kinase 3β (GSK3β) decreases inflammatory responses in brain endothelial cells. Am J Pathol 176:881–892PubMedGoogle Scholar
  563. Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K, Guimaraes A, Yue M, Lewis J, Carlson G, Hutton M, Ashe KH (2005) Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci 25:10637–10647PubMedGoogle Scholar
  564. Rao JS, Kellom M, Kim HW, Rapoport SI, Reese EA (2012) Neuroinflammation and synaptic loss. Neurochem Res 37:903–910PubMedGoogle Scholar
  565. Rattenborg NC, Martinez-Gonzalez D, Roth TC 2nd, Pravosudov VV (2011) Hippocampal memory consolidation during sleep: a comparison of mammals and birds. Biol Rev Camb Philos Soc 86:658–691PubMedGoogle Scholar
  566. Raz N, Gunning-Dixon F, Head D, Rodrigue KM, Williamson A, Acker JD (2004) Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume. Neurobiol Aging 25:377–396PubMedGoogle Scholar
  567. Raz N, Rodrigue KM, Kennedy KM, Acker JD (2007) Vascular health and longitudinal changes in brain and cognition in middle-aged and older adults. Neuropsychology 21:149–157PubMedGoogle Scholar
  568. Reagan L (2005) Neuronal insulin signal transduction mechanisms in diabetes phenotypes. Neurobiol Aging 26:56–59PubMedGoogle Scholar
  569. Rebola N, Srikumar BN, Mulle C (2010) Activity-dependent synaptic plasticity of NMDA receptors. J Physiol 588:93–99PubMedGoogle Scholar
  570. Recinto P, Samant AR, Chavez G, Kim A, Yuan CJ, Soleiman M, Grant Y, Edwards S, Wee S, Koob GF, George O, Mandyam CD (2012) Levels of neural progenitors in the hippocampus predict memory impairment and relapse to drug seeking as a function of excessive methamphetamine self-administration. Neuropsychopharmacology 37:1275–1287PubMedGoogle Scholar
  571. Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, Kaye J, Manczak M (2005) Differential loss of synaptic proteins in Alzheimer’s disease: implications for synaptic dysfunction. J Alzheimers Dis 7:103–117PubMedGoogle Scholar
  572. Redwine JM, Kosofsky B, Jacobs RE, Games D, Reilly JF, Morrison JH, Young WG, Bloom FE (2003) Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis. Proc Natl Acad Sci USA 100:1381–1386PubMedGoogle Scholar
  573. Reitz C, Brickman AM, Brown TR, Manly J, DeCarli C, Small SA, Mayeux R (2009) Linking hippocampal structure and function to memory performance in an aging population. Arch Neurol 66:1385–1392PubMedGoogle Scholar
  574. Resende LS, Ribeiro AM, Werner D, Hall JM, Savage LM (2012) Thiamine deficiency degrades the link between spatial behavior and hippocampal synapsin I and phosphorylated synapsin I protein levels. Behav Brain Res 232:421–425PubMedGoogle Scholar
  575. Rice AC, Bullock MR, Shelton KL (2004) Chronic ethanol consumption transiently reduces adult neural progenitor cell proliferation. Brain Res 1011:94–98Google Scholar
  576. Richard E, Reitz C, Honig LH, Schupf N, Tang MX, Manly JJ, Mayeux R, Devanand D, Luchsinger JA (2012) Late-life depression, mild cognitive impairment, and dementia. Arch Neurol 31:1–7. doi:10.1001/jamaneurol.2013.603 Google Scholar
  577. Richwine AF, Godbout JP, Berg BM, Chen J, Escobar J, Millard DK, Johnson RW (2005) Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production. Brain Behav Immun 19:512–520PubMedGoogle Scholar
  578. Riddle W, O’Carroll RE, Dougall N, Van Beck M, Murray C, Curran SM, Ebmeier KP, Goodwin GM (1993) A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia. Br J Psychiatry 163:166–172PubMedGoogle Scholar
  579. Ridley RJ, Draper B, Withall A (2013) Alcohol-related dementia: an update of the evidence. Alzheimer’s Res Therapy 5:3Google Scholar
  580. Rissman RA, Staup MA, Lee AR, Justice NJ, Rice KC, Vale W, Sawchenko PE (2012) Corticotropin-releasing factor receptor-dependent effects of repeated stress on tau phosphorylation, solubility, and aggregation. Proc Natl Acad Sci USA 109:6277–6282PubMedGoogle Scholar
  581. Robitsek RJ, Fortin NJ, Koh MT, Gallagher M, Eichenbaum H (2008) Cognitive aging: a common decline of episodic recollection and spatial memory in rats. J Neurosci 28:8945–8954PubMedGoogle Scholar
  582. Rodríguez-Vázquez J, Camacho-Arroyo I, Velázquez-Moctezuma J (2012) Differential impact of REM sleep deprivation on cytoskeletal proteins of brain regions involved in sleep regulation. Neuropsychobiology 65:161–167PubMedGoogle Scholar
  583. Roh MS, Eom TY, Zmijewska AA, De Sarno P, Roth KA, Jope RS (2005) Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: protection by mood stabilizers and imipramine. Biol Psychiatry 57:278–286PubMedGoogle Scholar
  584. Rolyan H, Scheffold A, Heinrich A, Begus-Nahrmann Y, Langkopf BH, Hölter SM, Vogt-Weisenhorn DM, Liss B, Wurst W, Lie DC, Thal DR, Biber K, Rudolph KL (2011) Telomere shortening reduces Alzheimer’s disease amyloid pathology in mice. Brain 134:2044–2056PubMedGoogle Scholar
  585. Roozendaal B, Griffith QK, Buranday J, De Quervain DJ, McGaugh JL (2003) The hippocampus mediates glucocorticoid- induced impairment of spatial memory retrieval: dependence on the basolateral amygdala. Proc Natl Acad Sci USA 100:1328–1333PubMedGoogle Scholar
  586. Rosi S, Pert CB, Ruff MR, McGann-Gramling K, Wenk GL (2005a) Chemokine receptor 5 antagonist D-Ala-peptide T- amide reduces microglia and astrocyte activation within the hippocampus in a neuroinflammatory rat model of Alzheimer’s disease. Neuroscience 134:671–676PubMedGoogle Scholar
  587. Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF, Barnes CA, Wenk GL (2005b) Neuroinflammation alters the hippocampal pattern of behaviorally induced Arc expression. J Neurosci 25:723–731PubMedGoogle Scholar
  588. Ross RS, Sherrill KR, Stern CE (2011) The hippocampus is functionally connected to the striatum and orbitofrontal cortex during context dependent decision making. Brain Res 1423:53–66PubMedGoogle Scholar
  589. Rössler M, Zarski R, Bohl J, Ohm TG (2002) Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer’s disease. Acta Neuropathol 103:363–369PubMedGoogle Scholar
  590. Row BW (2007) Intermittent hypoxia and cognitive function: implications from chronic animal models. Adv Exp Med Biol 618:51–67PubMedGoogle Scholar
  591. Rusch BD, Abercrombie HC, Oakes TR, Schaefer SM, Davidson RJ (2001) Hippocampal morphometry in depressed patients and control subjects: relations to anxiety symptoms. Biol Psychiatry 50:960–964PubMedGoogle Scholar
  592. Rutten BP, Van der Kolk NM, Schafer S, van Zandvoort MA, Bayer TA, Steinbusch HW, Schmitz C (2005) Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167:161–173PubMedGoogle Scholar
  593. Ryder J, Su Y, Liu F, Li B, Zhou Y, Ni B (2003) Divergent roles of GSK3 and CDK5 in APP processing. Biochem Biophys Res Commun 312:922–929PubMedGoogle Scholar
  594. Sabbatini M, Tomassoni D, Amenta F (2001) Hypertensive brain damage: comparative evaluation of protective effect of treatment with dihydropyridine derivatives in spontaneously hypertensive rats. Mech Ageing Dev 122:2085–2105PubMedGoogle Scholar
  595. Sabbatini M, Catalani A, Consoli C, Marletta N, Tomassoni D, Avola R (2002) The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia? Mech Ageing Dev 123:547–559PubMedGoogle Scholar
  596. Sabia S, Elbaz A, Dugravot A, Head J, Shipley M, Hagger-Johnson G, Kivimaki M, Singh-Manoux A (2012) Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study. Arch Gen Psychiatry 69:627–635PubMedGoogle Scholar
  597. Sachdev PS (2011) Alzheimer disease: homocysteine and Alzheimer disease: an intervention study. Nat Rev Neurol 7:9–10PubMedGoogle Scholar
  598. Sadowski M, Pankiewicz J, Scholtzova H, Ji Y, Quartermain D, Jensen CH, Duff K, Nixon RA, Gruen RJ, Wisniewski T (2004) Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice. J Neuropathol Exp Neurol 63:418–428PubMedGoogle Scholar
  599. Sairanen M, Lucas G, Ernfors P, Castrén M, Castrén E (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25:1089–1094PubMedGoogle Scholar
  600. Sametsky EA, Disterhoft JF, Geinisman Y, Nicholson DA (2008) Synaptic strength and postsynaptically silent synapses through advanced aging in rat hippocampal CA1 pyramidal neurons. Neurobiol Aging 31:813–825PubMedGoogle Scholar
  601. Sanacora G, Treccani G, Popoli M (2012) Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 62:63–77PubMedGoogle Scholar
  602. Sastre-Garriga J, Ingle GT, Chard DT, Ramio-Torrenta L, McLean MA, Miller DH, Thompson AJ (2005) Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 62:569–573PubMedGoogle Scholar
  603. Savage LM, Hall JM, Resende LS (2012) Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery. Neuropsychol Rev 22:195–209PubMedGoogle Scholar
  604. Saylam C, Ucerler H, Kitis O, Ozand E, Gönül AS (2006) Reduced hippocampal volume in drug-free depressed patients. Surg Radiol Anat 28:82–87PubMedGoogle Scholar
  605. Scahill RI, Frost C, Jenkins R, Whitwell JL, Rossor MN, Fox NCA (2003) longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 60:989–994PubMedGoogle Scholar
  606. Schaffer BA, Bertram L, Miller BL, Mullin K, Weintraub S, Johnson N, Bigio EH, Mesulam M, Wiedau-Pazos M, Jackson GR, Cummings JL, Cantor RM, Levey AI, Tanzi RE, Geschwind DH (2008) Association of GSK3B with alzheimer disease and frontotemporal dementia. Arch Neurol 65:1368–1374PubMedGoogle Scholar
  607. Scheef L, Spottke A, Daerr M, Joe A, Striepens N, Kölsch H, Popp J, Daamen M, Gorris D, Heneka MT, Boecker H, Biersack HJ, Maier W, Schild HH, Wagner M, Jessen F (2012) Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment. Neurology 79:1332–1339PubMedGoogle Scholar
  608. Scheff SW, Price DA (2001) Alzheimer’s disease-related synapse loss in the cingulate cortex. J Alzheimers Dis 3:495–505PubMedGoogle Scholar
  609. Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27:1372–1384PubMedGoogle Scholar
  610. Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ (2007) Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68:1501–1508PubMedGoogle Scholar
  611. Schindowski K, Bretteville A, Leroy K, Bégard S, Brion JP, Hamdane M, Buée L (2006) Alzheimer’s disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol 169:599–616PubMedGoogle Scholar
  612. Schlachetzki JC, Hüll M (2009) Microglial activation in Alzheimer’s disease. Curr Alzheimer Res 6:554–563PubMedGoogle Scholar
  613. Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD (1993) Increased amyloid betapeptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 90:9649–9653PubMedGoogle Scholar
  614. Schmitz C, Rutten BP, Pielen A, Schafer S, Wirths O, Tremp G, Czech C, Blanchard V, Multhaup G, Rezaie P, Korr H, Steinbusch HW, Pradier L, Bayer TA (2004) Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer’s disease. Am J Pathol 164:1495–1502PubMedGoogle Scholar
  615. Schonheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697–711PubMedGoogle Scholar
  616. Schuff N, Amend DL, Knowlton R, Norman D, Fein G, Weiner MW (1999) Age-related metabolite changes and volume loss in the hippocampus by magnetic resonance spectroscopy and imaging. Neurobiol Aging 20:279–285PubMedGoogle Scholar
  617. Schuff N, Woerner N, Boreta L, Kornfield T, Shaw LM, Trojanowski JQ, Thompson PM, Jack CR Jr, Weiner MW (2009) MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain 132:1067–1077PubMedGoogle Scholar
  618. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:11–21PubMedGoogle Scholar
  619. Seckl JR, Olsson T (1995) Glucocorticoid hypersecretion and the age-impaired hippocampus: cause or effect? J Endocrinol 145:201–211PubMedGoogle Scholar
  620. Sepehry AA, Lee PE, Hsiung GY, Beattie BL, Jacova C (2012) Effect of selective serotonin reuptake inhibitors in Alzheimer’s disease with comorbid depression: a meta-analysis of depression and cognitive outcomes. Drugs Aging 29:793–806PubMedGoogle Scholar
  621. Sereno L, Coma M, Rodriguez M, Sanchez-Ferrer P, Sanchez MB, Gich I, Agullo JM, Perez M, Avila J, Guardia-Laguarta C, Clarimon J, Lleo A, Gomez-Isla T (2009) A novel GSK-3beta inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis 35:359–367PubMedGoogle Scholar
  622. Seripa D, Panza F, Franceschi M, D’Onofrio G, Solfrizzi V, Dallapiccola B, Pilotto A (2009) Non-apolipoprotein E and apolipoprotein E genetics of sporadic Alzheimer’s disease. Ageing Res Rev 8:214–236PubMedGoogle Scholar
  623. Serra L, Perri R, Cercignani M, Spanò B, Fadda L, Marra C, Carlesimo GA, Caltagirone C, Bozzali M (2010) Are the behavioral symptoms of Alzheimer’s disease directly associated with neurodegeneration? J Alzheimer Dis 21:627–639Google Scholar
  624. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346:476–483PubMedGoogle Scholar
  625. Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK (2002) Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105:2462–2464PubMedGoogle Scholar
  626. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL (2007) Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor- dependent signaling pathway. J Neurosci 27:2866–2875PubMedGoogle Scholar
  627. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842PubMedGoogle Scholar
  628. Shaw KN, Commins S, O’Mara SM (2005) Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation. Brain Res 1038:231–237PubMedGoogle Scholar
  629. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93:3908–3913PubMedGoogle Scholar
  630. Sheline YI, Sanghavi M, Mintun MA, Gado MH (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19:5034–5043PubMedGoogle Scholar
  631. Sheng JG, Price DL, Koliatsos VE (2002) Disruption of corticocortical connections ameliorates amyloid burden in terminal fields in a transgenic model of Abeta amyloidosis. J Neurosci 22:9794–9799PubMedGoogle Scholar
  632. Shi L, Linville MC, Tucker EW, Sonntag WE, Brunso-Bechtold JK (2005) Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus. Cereb Cortex 15:571–577PubMedGoogle Scholar
  633. Shimokata H, Muller DC, Fleg JL, Sorkin J, Ziemba AW, Andres R (1991) Age as independent determinant of glucose tolerance. Diabetes 40:44–51PubMedGoogle Scholar
  634. Shin J, Yu S-B, Yu UY, Jo SA, Ahn J-H (2010) Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer’s disease. BMB Reports 43:704–709PubMedGoogle Scholar
  635. Shinohara M, Yamada M (2012) Drug-induced cognitive impairment. Brain Nerve 64(12):1405–1410PubMedGoogle Scholar
  636. Shukla C, Bridges LR (2001) Tau, beta-amyloid and beta-amyloid precursor protein distribution in the entorhinal–hippocampal alvear and perforant pathways in the Alzheimer’s brain. Neurosci Lett 303:193–197PubMedGoogle Scholar
  637. Simmons NE, Do HM, Lipper MH, Laws ER Jr (2000) Cerebral atrophy in Cushing’s disease. Surg Neurol 53:72–76PubMedGoogle Scholar
  638. Small SA (2001) Age-related memory decline: current concepts and future directions. Arch Neurol (Chicago) 58:360–364Google Scholar
  639. Small SA, Tsai WY, DeLaPaz R, Mayeux R, Stern Y (2002) Imaging hippocampal function across the human life span: is memory decline normal or not? Ann Neurol 51:290–295PubMedGoogle Scholar
  640. Small SA, Chawla MK, Buonocore M, Rapp PR, Barnes CA (2004a) From The Cover: Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc Natl Acad Sci USA 101:7181–7186PubMedGoogle Scholar
  641. Small SA, Chawla MK, Buonocore M, Rapp PR, Barnes CA (2004b) Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc Natl Acad Sci USA 101:7181–7186PubMedGoogle Scholar
  642. Smith TD, Adams MM, Gallagher M, Morrison JH, Rapp PR (2000) Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. J Neurosci 20:6587–6593Google Scholar
  643. Smith MA, Zhu X, Tabaton M, Liu G, McKeel DW, Cohen ML, Wang X, Siedlak SL, Dwyer BE, Hayashi T, Nakamura M, Nunomura A, Perry G (2010) Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimers Dis 19:363–372PubMedGoogle Scholar
  644. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 8:1051–1058PubMedGoogle Scholar
  645. Snyder JS, Choe JS, Clifford MA, Jeurling SI, Hurley P, Brown A, Kamhi JF, Cameron HA (2009) Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice. J Neurosci 29:14484–14495PubMedGoogle Scholar
  646. Sojkova J, Beason-Held L, Zhou Y, An Y, Kraut MA, Ye W, Ferrucci L, Mathis CA, Klunk WE, Wong DF, Resnick SM (2008) Longitudinal cerebral blood flow and amyloid deposition: an emerging pattern? J Nucl Med 49:1465–1471PubMedGoogle Scholar
  647. Sojkova J, Zhou Y, An Y, Kraut MA, Ferrucci L, Wong DF, Resnick SM (2011) Longitudinal patterns of β-amyloid deposition in nondemented older adults. Arch Neurol 68:644–649PubMedGoogle Scholar
  648. Sommer G, Kralisch S, Lipfert J, Weise S, Krause K, Jessnitzer B, Lössner U, Blüher M, Stumvoll M, Fasshauer M (2009) Amyloid precursor protein expression is induced by tumor necrosis factor alpha in 3T3-L1 adipocytes. J Cell Biochem 108:1418–1422PubMedGoogle Scholar
  649. Sonntag WE, Lynch CD, Cooney PT, Hutchins PM (1997) Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology 138:3515–3520PubMedGoogle Scholar
  650. Sorisky A (2002) Molecular links between obesity and cardiovascular disease. Am J Ther 9:516–521PubMedGoogle Scholar
  651. Souza LC, Filho CB, Goes AT, Fabbro LD, de Gomes MG, Savegnago L, Oliveira MS, Jesse CR (2013) Neuroprotective effect of physical exercise in a mouse model of Alzheimer’s disease induced by β-amyloid(1–40) peptide. Neurotox Res. doi:10.1007/s12640-012-9373-0
  652. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315PubMedGoogle Scholar
  653. Sparks DL, Scheff SW, Liu H, Landers TM, Coyne CM, Hunsaker JC III (1995) Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension. J Neurol Sci 131:162–169PubMedGoogle Scholar
  654. Sportiche N, Suntsova N, Methippara M, Bashir T, Mitrani B, Szymusiak R, McGinty D (2010) Sustained sleep fragmentation results in delayed changes in hippocampal-dependent cognitive function associated with reduced dentate gyrus neurogenesis. Neuroscience 170:247–258PubMedGoogle Scholar
  655. Squire LR (1992) Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99:195–231PubMedGoogle Scholar
  656. Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306PubMedGoogle Scholar
  657. Stéphan A, Laroche S, Davis S (2001) Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits. J Neurosci 21:5703–5714PubMedGoogle Scholar
  658. Stoub TR, deToledo-Morrell L, Stebbins GT, Leurgans S, Bennett DA, Shah RC (2006) Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci USA 103:10041–10045PubMedGoogle Scholar
  659. Stranahan AM (2011) Physiological variability in brain-derived neurotrophic factor expression predicts dendritic spine density in the mouse dentate gyrus. Neurosci Lett 495:60–62PubMedGoogle Scholar
  660. Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS, Egan JM, Mattson MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088PubMedGoogle Scholar
  661. Stranahan AM, Haberman RP, Gallagher M (2010) Cognitive decline is associated with reduced reelin expression in the entorhinal cortex of aged rats. Cereb Cortex 21:392–400PubMedGoogle Scholar
  662. Su Y, Ni B (1998) Selective deposition of amyloid-beta protein in the entorhinal-dentate projection of a transgenic mouse model of Alzheimer’s disease. J Neurosci Res 53:177–186PubMedGoogle Scholar
  663. Su Y, Ryder J, Li B, Wu X, Fox N, Solenberg P, Brune K, Paul S, Zhou Y, Liu F, Ni B (2004) Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry 43:6899–6908PubMedGoogle Scholar
  664. Sun MK, Alkon DL (2004) Cerebral hypoperfusion and amyloid-induced synergistic impairment of hippocampal CA1 synaptic efficacy and spatial memory in young adult rats. J Alzheimers Dis 6:355–366PubMedGoogle Scholar
  665. Sun X, Sato S, Murayama O, Murayama M, Park JM, Yamaguchi H, Takashima (2002) A lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neurosci Lett 321:61–64PubMedGoogle Scholar
  666. Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M (1998) Alzheimer’s beta-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Res 807:110–117PubMedGoogle Scholar
  667. Sweatt JD (2004) Hippocampal function in cognition. Psychopharmacology 174:99–110PubMedGoogle Scholar
  668. Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, D’Hooge R, Alzheimer C, Mandelkow EM (2011) Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 31:2511–2525PubMedGoogle Scholar
  669. Takayama N, Iseki E, Yamamoto T, Kosaka K (2002) Regional quantitative study of formation process of neurofibrillary tangles in the hippocampus of non-demented elderly brains: comparison with late-onset Alzheimer’s disease brains. Neuropathology 22:147–153PubMedGoogle Scholar
  670. Tamaru M, Yoneda Y, Ogita K, Shimizu J, Nagata Y (1991) Age-related decreases of the N-methyl-d-aspartate receptor complex in the rat cerebral cortex and hippocampus. Brain Res 542:83–90PubMedGoogle Scholar
  671. Tamminga CA, Southcott S, Sacco C, Wagner AD, Ghose S (2012) Glutamate dysfunction in hippocampus: relevance of dentate gyrus and CA3 signaling. Schizophr Bull 38:927–935PubMedGoogle Scholar
  672. Tancredi V, D’Antuono M, Cafè C, Giovedì S, Buè MC, D’Arcangelo G, Onofri F, Benfenati F (2000) The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK. J Neurochem 75:634–643PubMedGoogle Scholar
  673. Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208:1–25PubMedGoogle Scholar
  674. Tateno M, Saito T (2008) Biological studies on alcohol-induced neuronal damage. Psychiatry Investig 5:21–27PubMedGoogle Scholar
  675. Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, Krishnan KR (2005) Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry 62:537–544PubMedGoogle Scholar
  676. Terry RD, DeTeresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol 21:530–539PubMedGoogle Scholar
  677. Terwel D, Muyllaert D, Dewachter I, Borghgraef P, Croes S, Devijver H, Leuven FV (2008) Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol 172:786–798PubMedGoogle Scholar
  678. Thal DR, Holzer M, Rub U, Waldmann G, Gunzel S, Zedlick D, Schober R (2000) Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 163:98–110Google Scholar
  679. Thibault O, Hadley R, Landfield PW (2001) Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity. J Neurosci 21:9744–9756PubMedGoogle Scholar
  680. Thirumangalakudi L, Prakasam A, Zhang R, Bimonte-Nelson H, Sambamurti K, Kindy MS, Bhat NR (2008) High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice. J Neurochem 106:475–485PubMedGoogle Scholar
  681. Thomas RM, Hotsenpiller G, Peterson DA (2007) Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation. J Neurosci 27:2734–2743PubMedGoogle Scholar
  682. Tian M, Zhu D, Xie W, Shi J (2012) Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett 586(20):3737–3745PubMedGoogle Scholar
  683. Tilvis RS, Kähönen-Väre MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE (2004) Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 59:268–274PubMedGoogle Scholar
  684. Trayhurn P, Wood IS (2005) Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 33:1078–1081PubMedGoogle Scholar
  685. Trivedi MA, Schmitz TW, Ries ML, Torgerson BM, Sager MA, Hermann BP, Asthana S, Johnson SC (2006) Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer’s disease: a cross-sectional study. BMC Med 4:1PubMedGoogle Scholar
  686. Troen AM, Shea-Budgell M, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH (2008) B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice. Proc Natl Acad Sci USA 105:12474–12479PubMedGoogle Scholar
  687. Trouche S, Bontempi B, Roullet P, Rampon C (2009) Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory. Proc Natl Acad Sci USA 106:5919–5924PubMedGoogle Scholar
  688. Ueno M, Sakamoto H, Tomimoto H, Akiguchi I, Onodera M, Huang CL, Kanenishi K (2004) Blood–brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats. Acta Neuropathol 107:532–538PubMedGoogle Scholar
  689. Umegaki H (2012) Neurocognitive dysfunction in old diabetics: management and treatment. Adv Exp Med Biol 771:465–470PubMedGoogle Scholar
  690. Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, Yurgelun-Todd DA (2000) Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry 47:1087–1090PubMedGoogle Scholar
  691. Van der Jeugd A, Ahmed T, Burnouf S, Belarbi K, Hamdame M, Grosjean ME, Humez S, Balschun D, Blum D, Buée L, D’Hooge R (2011) Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. Neurobiol Learn Mem 95:296–304PubMedGoogle Scholar
  692. Van der Jeugd A, Hochgräfe K, Ahmed T, Decker JM, Sydow A, Hofmann A, Wu D, Messing L, Balschun D, D’Hooge R, Mandelkow EM (2012) Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau. Acta Neuropathol 123(6):787–805PubMedGoogle Scholar
  693. Van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034PubMedGoogle Scholar
  694. VanGuilder HD, Yan H, Farley JA, Sonntag WE, Freeman WM (2010) Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome. J Neurochem 113:1577–1588PubMedGoogle Scholar
  695. VanGuilder HD, Farley JA, Yan H, Van Kirk CA, Mitschelen M, Sonntag WE, Freeman WM (2011) Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline. Neurobiol Dis 43:201–212PubMedGoogle Scholar
  696. VanGuilder HD, Bixler GV, Sonntag WE, Freeman WM (2012) Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory. J Neurochem 121:77–98PubMedGoogle Scholar
  697. Varela-Nallar L, Aranguiz FC, Abbott AC, Slater PG, Inestrosa NC (2010) Adult hippocampal neurogenesis in aging and Alzheimer’s disease. Birth Defects Res C Embryo Today 90:284–296PubMedGoogle Scholar
  698. Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin W (1997) Differential effects of early hippocampal pathology on episodic and semantic memory. Science 277:376–380PubMedGoogle Scholar
  699. Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M, Houslay MD, Abel T (2009) Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461:1122–1125Google Scholar
  700. Venkateshappa C, Harish G, Mahadevan A, Srinivas Bharath MM, Shankar SK (2012) Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer’s disease. Neurochem Res 37:1601–1614PubMedGoogle Scholar
  701. Venugopal SK, Devaraj S, Yuhanna I, Shaul P, Jialal I (2002) Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 106(12):1439–1441PubMedGoogle Scholar
  702. Verbaten MN (2009) Chronic effects of low to moderate alcohol consumption on structural and functional properties of the brain: beneficial or not? Hum Psychopharmacol 24:199–205PubMedGoogle Scholar
  703. Vermetten E, Bremner JD (2002) Circuits and systems in stress. I. Preclinical studies. Depress Anxiety 15:126–147PubMedGoogle Scholar
  704. Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD (2003) Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry 54:693–702PubMedGoogle Scholar
  705. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 82:1313–1316PubMedGoogle Scholar
  706. Vgontzas AN, Zoumakis M, Bixler EO, Lin HM, Prolo P, Vela-Bueno A, Kales A, Chrousos GP (2003) Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: physiologic and therapeutic implications. J Clin Endocrinol Metab 88:2087–2095PubMedGoogle Scholar
  707. Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Follett H, Kales A, Chrousos GP (2004) Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab 89:2119–2126PubMedGoogle Scholar
  708. Vicario A, Martinez CD, Baretto D, Diaz Casale A, Nicolosi L (2005) Hypertension and cognitive decline: impact on executive function. J Clin Hypertens (Greenwich) 7:598–604Google Scholar
  709. Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161:1957–1966PubMedGoogle Scholar
  710. Videbech P, Ravnkilde B, Pedersen TH, Hartvig H, Egander A, Clemmensen K, Rasmussen NA, Andersen F, Gjedde A, Rosenberg R (2002) The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis. Acta Psychiatr Scand 106:35–44PubMedGoogle Scholar
  711. Vines A, Cahoon S, Goldberg I, Saxena U, Pillarisetti S (2006) Novel anti-inflammatory role for glycogen synthase kinase-3beta in the inhibition of tumor necrosis factor-alpha- and interleukin-1beta-induced inflammatory gene expression. J Biol Chem 281:16985–16990PubMedGoogle Scholar
  712. Volk LJ, Bachman JL, Johnson R, Yu Y, Huganir RL (2013) PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory. Nature 493:420–423PubMedGoogle Scholar
  713. von Känel R, Dimsdale JE, Ancoli-Israel S, Mills PJ, Patterson TL, McKibbin CL, Archuleta C, Grant I (2006) Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc 54:431–437Google Scholar
  714. Waldstein SR, Brown JR, Maier KJ, Katzel LI (2005a) Diagnosis of hypertension and high blood pressure levels negatively affect cognitive function in older adults. Ann Behav Med 29:174–180PubMedGoogle Scholar
  715. Waldstein SR, Giggey PP, Thayer JF, Zonderman AB (2005b) Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging. Hypertension 45:374–379PubMedGoogle Scholar
  716. Walhovd KB, Fjell AM, Reinvang I, Lundervold A, Dale AM, Eilertsen DE, Quinn BT, Salat D, Makris N, Fischl B (2005) Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiol Aging 26:1261–1270PubMedGoogle Scholar
  717. Walhovd KB, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Fjell AM (2011) Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiol Aging 32:916–932PubMedGoogle Scholar
  718. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–539PubMedGoogle Scholar
  719. Wan Q, Liu Y, Guan Q, Gao L, Lee KO, Zhao J (2005) Ethanol feeding impairs insulin-stimulated glucose uptake in isolated rat skeletal muscle: role of Gs alpha and cAMP. Alcohol Clin Exp Res 29:1450–1456PubMedGoogle Scholar
  720. Wang L, Miller JP, Gado MH, McKeel D, Rothermich M, Miller MI, Morris JC, Csernansky JG (2006a) Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type. Neuroimage 30:52–60PubMedGoogle Scholar
  721. Wang L, Zang Y, He Y, Liang M, Zhang X, Tian L, Wu T, Jiang T, Li K (2006b) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage 31:496–504PubMedGoogle Scholar
  722. Wang Y, Cui H, Wang W, Zhao B, Lai J (2012) The region-specific activation of Ca(2+)/calmodulin dependent protein kinase II and extracellular signal-regulated kinases in hippocampus following chronic alcohol exposure. Brain Res Bull 89:191–196PubMedGoogle Scholar
  723. Wang B, Yan B, Song D, Ye X, Liu SF (2013) Chronic intermittent hypoxia down-regulates endothelial nitric oxide synthase expression by an NF-κB-dependent mechanism. Sleep Med 14:165–171PubMedGoogle Scholar
  724. Ward RJ, Colivicchi MA, Allen R, Schol F, Lallemand F, de Witte P, Ballini C, Corte LD, Dexter D (2009) Neuro- inflammation induced in the hippocampus of ‘binge drinking’ rats may be mediated by elevated extracellular glutamate content. J Neurochem 111:1119–1128PubMedGoogle Scholar
  725. Weber A, Dzietko M, Berns M, Felderhoff-Mueser U, Heinemann U, Maier RF, Obladen M, Ikonomidou C, Bührer C (2005) Neuronal damage after moderate hypoxia and erythropoietin. Neurobiol Dis 20:594–600PubMedGoogle Scholar
  726. Wehling M (2012) Medication in the elderly: cognitive impairment by drugs. Internist (Berl) 53:1240–1247Google Scholar
  727. Wei W, Liu YH, Zhang CE, Wang Q, Wei Z, Mousseau DD, Wang JZ, Tian Q, Liu GP (2011) Folate/vitamin-B12 prevents chronic hyperhomocysteinemia-induced tau hyperphosphorylation and memory deficits in aged rats. J Alzheimers Dis 27:639–650PubMedGoogle Scholar
  728. Wells AM, Janes AC, Liu X, Deschepper CF, Kaufman MJ, Kantak KM (2010) Medial temporal lobe functioning and structure in the spontaneously hypertensive rat: comparison with Wistar–Kyoto normotensive and Wistar–Kyoto hypertensive strains. Hippocampus 20:787–797PubMedGoogle Scholar
  729. Weniger G, Lange C, Irle E (2006) Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. J Affect Disord 94:219–229PubMedGoogle Scholar
  730. Wenz F, Rempp K, Brix G, Knopp MV, Gückel F, Hess T, van Kaick G (1996) Age dependency of the regional cerebral blood volume (rCBV) measured with dynamic susceptibility contrast MR imaging (DSC). Magn Reson Imaging 14:157–162PubMedGoogle Scholar
  731. West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14:287–293PubMedGoogle Scholar
  732. West MJ, Coleman PD, Flood DG, Troncoso JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 344(8925):769–772PubMedGoogle Scholar
  733. West MJ, Kawas CH, Martin LJ, Troncoso JC (2000) The CA1 region of the human hippocampus is a hot spot in Alzheimer’s disease. Ann N Y Acad Sci 908:255–259PubMedGoogle Scholar
  734. Westerberg CE, Mander BA, Florczak SM, Weintraub S, Mesulam MM, Zee PC, Paller KA (2012) Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. J Int Neuropsychol Soc 18:490–500PubMedGoogle Scholar
  735. Whatmough C, Chertkow H (2007) rCBF to the hippocampal complex covaries with superior semantic memory retrieval. Behav Brain Res 181(2):262–269PubMedGoogle Scholar
  736. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097PubMedGoogle Scholar
  737. Whitmer RA (2007) The epidemiology of adiposity and dementia. Curr Alzheimer Res 4:117–122PubMedGoogle Scholar
  738. Whitmer RA, Gunderson EP, Quesenberry CP, Zhou J, Yaffe K (2007) Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 4:103–109PubMedGoogle Scholar
  739. Wickelgren I (1998) Tracking insulin to the mind. Science 280:517–519PubMedGoogle Scholar
  740. Wilhelm J, Frieling H, Hillemacher T, Degner D, Kornhuber J, Bleich S (2008) Hippocampal volume loss in patients with alcoholism is influenced by the consumed type of alcoholic beverage. Alcohol Alcohol 43:296–299PubMedGoogle Scholar
  741. Williams IL, Wheatcroft SB, Shah AM, Kearney MT (2002) Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes Relat Metab Disord 26:754–764PubMedGoogle Scholar
  742. Wilson IA, Ikonen S, McMahan RW, Gallagher M, Eichenbaum H, Tanila H (2003) Place cell rigidity correlates with impaired spatial learning in aged rats. Neurobiol Aging 24:297–305PubMedGoogle Scholar
  743. Wilson IA, Ikonen S, Gureviciene I, McMahan RW, Gallagher M, Eichenbaum H, Tanila H (2004) Cognitive aging and the hippocampus: how old rats represent new environments. J Neurosci 24:3870–3878PubMedGoogle Scholar
  744. Wilson IA, Gallagher M, Eichenbaum H, Tanila H (2006) Neurocognitive aging: prior memories hinder new hippocampal encoding. Trends Neurosci 29:662–670PubMedGoogle Scholar
  745. Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA (2001) Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett 306:116–120PubMedGoogle Scholar
  746. Wirths O, Bethge T, Marcello A, Harmeier A, Jawhar S, Lucassen PJ, Multhaup G, Brody DL, Esparza T, Ingelsson M, Kalimo H, Lannfelt L, Bayer TA (2010) Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases. J Neural Transm 117:85–96PubMedGoogle Scholar
  747. Wiseman RM, Saxby BK, Burton EJ, Barber R, Ford GA, O’Brien JT (2004) Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects. Neurology 63:1892–1897PubMedGoogle Scholar
  748. Wium-Andersen MK, Orsted DD, Nielsen SF, Nordestgaard BG (2012) Elevated C-reactive protein levels, psychological distress, and depression in 73 131 individuals. Arch Gen Psychiatry 24:1–9Google Scholar
  749. Wofford JL, Loehr LR, Schwartz E (1996) Acute cognitive impairment in elderly ED patients: etiologies and outcomes. Am J Emerg Med 14:649–653PubMedGoogle Scholar
  750. Wolters M, Ströhle A, Hahn A (2004) Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences. Z Gerontol Geriatr 37:109–135PubMedGoogle Scholar
  751. Woollard KJ, Phillips DC, Griffiths HR (2002) Direct modulatory effect of C-reactive protein on primary human monocyte adhesion to human endothelial cells. Clin Exp Immunol 130:256–262PubMedGoogle Scholar
  752. Wu RH, Bruening R, Noachtar S, Arnold S, Berchtenbreiter C, Bartenstein P, Drzezga A, Tatsch K, Reiser M (1999) MR measurement of regional relative cerebral blood volume in epilepsy. J Magn Reson Imaging 9:435–440PubMedGoogle Scholar
  753. Xie H, Leung KL, Chen L, Chan YS, Ng PC, Fok TF, Wing YK, Ke Y, Li AM, Yung WH (2010) Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity. Neurobiol Dis 40:155–162PubMedGoogle Scholar
  754. Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, Ensrud KE, Ancoli-Israel S, Stone KL (2011) Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 306:613–619PubMedGoogle Scholar
  755. Yamaguchi S, Meguro K, Itoh M, Hayasaka C, Shimada M, Yamazaki H, Yamadori A (1997) A decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer’s disease as shown by MRI and PET. J Neurol Neurosurg Psychiatry 62:596–600PubMedGoogle Scholar
  756. Yanagisawa M, Planel E, Ishiguro K, Fujita SC (1999) Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer’s disease. FEBS Lett 461:329–333PubMedGoogle Scholar
  757. Yassa MA, Muftuler LT, Stark CE (2010) Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo. Proc Natl Acad Sci USA 107:12687–12691PubMedGoogle Scholar
  758. Yassa MA, Mattfeld AT, Stark SM, Stark CEL (2011) Age-related memory deficits linked to circuit-specific disruptions in the hippocampus. PNAS 108:8873–8878PubMedGoogle Scholar
  759. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A (2012) Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics 130:e856–e864PubMedGoogle Scholar
  760. Ye SM, Johnson RW (2001) Regulation of interleukin-6 gene expression in brain of aged mice by nuclear factor kappaB. J Neuroimmunol 117:87–96PubMedGoogle Scholar
  761. Yki-Järvinen H, Westerbacka J (2000) Vascular actions of insulin in obesity. Int J Obes Relat Metab Disord 24:S25–S28PubMedGoogle Scholar
  762. Yucel K, McKinnon MC, Taylor VH, Macdonald K, Alda M, Young LT, MacQueen GM (2007) Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology 195:357–367PubMedGoogle Scholar
  763. Yucel K, Taylor VH, McKinnon MC, Macdonald K, Alda M, Young LT, MacQueen GM (2008) Bilateral hippocampal volume increase in patients with bipolar disorder and short-term lithium treatment. Neuropsychopharmacology 33:361–367PubMedGoogle Scholar
  764. Yuskaitis CJ, Jope RS (2009) Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal 21:264–273PubMedGoogle Scholar
  765. Zakzanis KK, Leach L, Kaplan E (1998) On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry Neuropsychol Behav Neurol 11:111–119PubMedGoogle Scholar
  766. Zeng Y, Zhao D, Xie CW (2010) Neurotrophins enhance CaMKII activity and rescue amyloid-β-induced deficits in hippocampal synaptic plasticity. J Alzheimers Dis 21:823–831PubMedGoogle Scholar
  767. Zhang J, Kong Q, Zhang Z, Ge P, Ba D, He W (2003) Telomere dysfunction of lymphocytes in patients with Alzheimer disease. Cogn Behav Neurol 16:170–176PubMedGoogle Scholar
  768. Zhang C, McNeil E, Dressler L, Siman R (2007) Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease. Exp Neurol 204:77–87Google Scholar
  769. Zhang CE, Tian Q, Wei W, Peng JH, Liu GP, Zhou XW, Wang Q, Wang DW, Wang JZ (2008) Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol Aging 29:1654–1665PubMedGoogle Scholar
  770. Zhang M, Huang K, Zhang Z, Ji B, Zhu H, Zhou K, Li Y, Yang J, Sun L, Wei Z, He G, Gao L, He L, Wan C (2011) Proteome alterations of cortex and hippocampus tissues in mice subjected to vitamin A depletion. J Nutr Biochem 22:1003–1008PubMedGoogle Scholar
  771. Zhang Q, Gao T, Luo Y, Chen X, Gao G, Gao X, Zhou Y, Dai J (2012) Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer’s disease. PLoS ONE 7:e33722PubMedGoogle Scholar
  772. Zhao W, Chen H, Xu H, Moore E, Meiri N, Quon MJ, Alkon DL (1999) Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J Biol Chem 274:34893–34902PubMedGoogle Scholar
  773. Zhao X, Lein ES, He A, Smith SC, Aston C, Gage FH (2001) Transcriptional profiling reveals strict boundaries between hippocampal subregions. J Comp Neurol. 441:187–196PubMedGoogle Scholar
  774. Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3–11PubMedGoogle Scholar
  775. Zhao N, Zhong C, Wang Y, Zhao Y, Gong N, Zhou G, Xu T, Hong Z (2008) Impaired hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency at early pre-pathological lesion stage. Neurobiol Dis 29:176–185PubMedGoogle Scholar
  776. Zhao Y, Pan X, Zhao J, Wang Y, Peng Y, Zhong C (2009) Decreased transketolase activity contributes to impaired hippocampal neurogenesis induced by thiamine deficiency. J Neurochem 111:537–546PubMedGoogle Scholar
  777. Zhao YN, Wang F, Fan YX, Ping GF, Yang JY, Wu CF (2013) Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure. Behav Brain Res 236:270–282PubMedGoogle Scholar
  778. Zharkovsky T, Kaasik A, Jaako K, Zharkovsky A (2003) Neurodegeneration and production of the new cells in the dentate gyrus of juvenile rat hippocampus after a single administration of ethanol. Brain Res 978:115–123PubMedGoogle Scholar
  779. Zhou Y, Dougherty JH Jr, Hubner KF, Bai B, Cannon RL, Hutson RK (2008) Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement 4:265–270PubMedGoogle Scholar
  780. Zhu X, Su B, Wang X, Smith MA, Perry G (2007) Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci 64:2202–2210PubMedGoogle Scholar
  781. Zola-Morgan S, Squire LR, Amaral DG (1986) Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci 6:2950–2967PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Sleep Disorders Group, Department of EEE, Melbourne School of EngineeringThe University of MelbourneMelbourneAustralia

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