Abstract
Sporadic Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary “first-tier pathologies.” Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson’s disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented—it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.
Similar content being viewed by others
References
Abdul HM, Calabrese V, Calvani M, Butterfield DA (2006) Acetyl-l-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1–42-mediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. J Neurosci Res 84:398–408
Acquas E, Wilson C, Fibiger HC (1998) Pharmacology of sensory stimulation-evoked increases in frontal cortical acetylcholine release. Neuroscience 85:73–83
Adachi T, Meguro K, Sato A, Sato Y (1990) Cutaneous stimulation regulates blood flow in cerebral cortex in anesthetized rats. NeuroReport 1:41–44
Adams RW, Lambert GA, Lance JW (1989) Stimulation of brainstem nuclei in the cat: effect on neuronal activity in the primary visual cortex of relevance to cerebral blood flow and migraine. Cephalalgia 9:107–118
Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Changes in the brain catecholamines in patients with dementia of Alzheimer. Br J Psychiatry 135:216–233
Ahmadian SS, Rezvanian A, Peterson M, Weintraub S, Bigio EH, Mesulam MM, Geula C (2015) Loss of calbindin-D28K is associated with the full range of tangle pathology within basal forebrain cholinergic neurons in Alzheimer’s disease. Neurobiol Aging 36:3163–3170
Aizenstein HJ, Clark KA, Butters MA, Cochran J, Stenger VA, Meltzer CC, Reynolds CF, Carter CS (2004) The BOLD hemodynamic response in healthy aging. J Cogn Neurosci 16:786–793
Akio S (1998) Cholinergic neural regulation of regional cerebral blood flow. Nippon Yakurigaku Zasshi 112:5P–9P
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421
Aldes LD, Boone TB (1985) Organization of projections from the principal sensory trigeminal nucleus to the hypoglossal nucleus in the rat. Exp Br Res 58:16–29
Alenda A, Nunez A (2004) Sensory-interference in rat primary somatosensory cortical neurons. Eur J Neurosci 19:766–770
Alescio-Lautier B, Michel BF, Herrera C, Elahmadi A, Chambon C, Touzet C, Paban V (2007) Visual and visuospatial short-term memory in mild cognitive impairment and Alzheimer disease: role of attention. Neuropsychologia 45:1948–1960
Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL (2007) Disruption of large-scale brain systems in advanced aging. Neuron 56:924–935
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 63:693–699
Appollonio I, Carabellese C, Magni E, Frattola L, Trabucchi M (1995) Sensory impairments and mortality in an elderly community population: a six-year follow-up study. Age Ageing 24:30–36
Arenkiel BR, Hasegawa H, Yi JJ, Larsen RS, Wallace ML, Philpot BD, Wang F, Ehlers MD (2011) Activity-induced remodeling of olfactory bulb microcircuits revealed by monosynaptic tracing. PLoS One 6:e29423
Arnáiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, Nordberg A (2001) Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. NeuroReport 12:851–855
Arnsten AF (2006) Fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways. J Clin Psychiatry 67:7–12
Arnsten AF, Contant TA (1992) Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology 108:159–169
Arnsten AF, Steere JC, Jentsch DJ, Li BM (1998) Noradrenergic influences on prefrontal cortical cognitive function: opposing actions at postjunctional alpha 1 versus alpha 2-adrenergic receptors. Adv Pharmacol 42:764–767
Aronoff R, Matyas F, Mateo C, Ciron C, Schneider B, Petersen CC (2010) Long-range connectivity of mouse primary somatosensory barrel cortex. Eur J Neurosci 31:2221–2233
Association Alzheimer’s (2014) Alzheimer’s disease facts and figures. Alzheimers Dement 10:e47–e92
Aston-Jones G, Bloom FE (1981) Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J Neurosci 1:887–900
Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450
Aston-Jones G, Ennis M, Pieribone VA, Nickell WT, Shipley MT (1986) The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 234:734–737
Aston-Jones G, Chiang C, Alexinsky T (1991) Discharge of noradrenergic locus coeruleus neurons in behaving rats and monkeys suggests a role in vigilance. Prog Brain Res 88:501–520
Aston-Jones G, Rajkowski J, Kubiak P, Alexinsky T (1994) Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task. J Neurosci 14:4467–4480
Aston-Jones G, Rajkowski J, Cohen J (1999) Role of locus coeruleus in attention and behavioral flexibility. Biol Psychiatry 46:1309–1320
Attems J, Thal DR, Jellinger KA (2012a) The relationship between subcortical tau pathology and Alzheimer’s disease. Biochem Soc Trans 40:711–715
Attems J, Thomas A, Jellinger K (2012b) Correlations between cortical and subcortical tau pathology. Neuropathol Appl Neurobiol 38:582–590
Auld DS, Kornecook TJ, Bastianetto S, Quirion R (2002) Alzheimer’s disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 68:209–245
Ay I, Napadow V, Ay H (2015) Electrical stimulation of the vagus nerve dermatome in the external ear is protective in rat cerebral ischemia. Brain Stimul 8:7–12
Bao JX, Kandel ER, Hawkins RD (1998) Involvement of presynaptic and postsynaptic mechanisms in a cellular analog of classical conditioning at Aplysia sensory-motor neuron synapses in isolated cell culture. J Neurosci 18:458–466
Barbas H, Zikopoulos B, Timbie C (2011) Sensory pathways and emotional context for action in primate prefrontal cortex. Biol Psychiatry 69:1133–1139
Barbelivien A, Bertrand N, Besret L, Beley A, MacKenzie ET, Dauphin F (1999) Neurochemical stimulation of the rat substantia innominata increases cerebral blood flow (but not glucose use) through the parallel activation of cholinergic and non-cholinergic pathways. Brain Res 840:115–124
Bardou I, Kaercher RM, Brothers HM, Hopp SC, Royer S, Wenk GL (2014) Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem. Neurobiol Aging 35:1065–1073
Barkai E (2005) Dynamics of learning-induced cellular modifications in the cortex. Biol Cybern 92:360–366
Barnes SJ, Finnerty GT (2010) Sensory experience and cortical rewiring. Neuroscientist 16:186–198
Bartesaghi R, Gessi T (2003) Activation of perforant path neurons to field CA1 by hippocampal projections. Hippocampus 13:235–249
Baskerville KA, Kent C, Nicolle MM, Gallagher M, McKinney M (2006) Aging causes partial loss of basal forebrain but no loss of pontine reticular cholinergic neurons. NeuroReport 17:1819–1823
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 63:97–101
Beckmann N, Schuler A, Mueggler T, Meyer EP, Wiederhold KH, Staufenbiel M, Krucker T (2003) Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer’s disease. J Neurosci 23:8453–8459
Beckstead RM, Norgren R (1979) An autoradiographic examination of the central distribution of the trigeminal, facial, glossopharyngeal, and vagal nerves in the monkey. J Comp Neurol 184:455–472
Bedwell SA, Billett EE, Crofts JJ, Tinsley CJ (2014) The topology of connections between rat prefrontal, motor and sensory cortices. Front Syst Neurosci 8:177
Bekar LK, He W, Nedergaard M (2008) Locus coeruleus alpha-adrenergic-mediated activation of cortical astrocytes in vivo. Cereb Cortex 18:2789–2795
Bekar LK, Wei HS, Nedergaard M (2012) The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand. J Cereb Blood Flow Metab 32:2135–2145
Bellucci A, Westwood AJ, Ingram E, Casamenti F, Goedert M, Spillantini MG (2004) Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol 165:1643–1652
Bellucci A, Bugiani O, Ghetti B, Spillantini MG (2011) Presence of reactive microglia and neuroinflammatory mediators in a case of frontotemporal dementia with P301S mutation. Neurodegener Dis 8:221–229
Benveniste EN, Nguyen VT, O’Keefe GM (2001) Immunological aspects of microglia: relevance to Alzheimer’s disease. Neurochem Int 39:381–391
Bergman E, Fundin BT, Ulfhake B (1999) Effects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons. J Comp Neurol 410:368–386
Berridge CW, Abercrombie ED (1999) Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis. Neuroscience 93:1263–1270
Berridge CW, Foote SL (1991) Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. J Neurosci 11:3135–3145
Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84
Berridge CW, Schmeichel BE, Espana RA (2012) Noradrenergic modulation of wakefulness/arousal. Sleep Med Rev 16:187–197
Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT (2010) Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68:19–31
Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL (1995) Neurochemical correlates of dementia severity in Alzheimer’s disease: relative importance of the cholinergic deficits. J Neurochem 64:749–760
Biesold D, Inanami O, Sato A, Sato Y (1989) Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci Lett 98:39–44
Birdsill AC, Carlsson CM, Willette AA, Okonkwo OC, Johnson SC, Xu G, Oh JM, Gallagher CL, Koscik RL, Jonaitis EM, Hermann BP, LaRue A, Rowley HA, Asthana S, Sager MA, Bendlin BB (2013) Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity (Silver Spring) 21:1313–1320
Bisogni V, Pengo MF, Maiolino G, Rossi GP (2016) The sympathetic nervous system and catecholamines metabolism in obstructive sleep apnoea. J Thorac Dis 8:243–254
Blalock EM, Grondin R, Chen KC, Thibault O, Thibault V, Pandya JD, Dowling A, Zhang Z, Sullivan P, Porter NM, Landfield PW (2010) Aging-related gene expression in hippocampus proper compared with dentate gyrus is selectively associated with metabolic syndrome variables in rhesus monkeys. J Neurosci 30:6058–6071
Blatow M, Nennig E, Durst A, Sartor K, Stippich C (2007) fMRI reflects functional connectivity of human somatosensory cortex. Neuroimage 37:927–936
Bodegard A, Geyer S, Naito E, Zilles K, Roland PE (2000) Somatosensory areas in man activated by moving stimuli: cytoarchitectonic mapping and PET. NeuroReport 11:187–191
Boissiere F, Faucheux B, Ruberg M, Agid Y, Hirsch EC (1997) Decreased TrkA gene expression in cholinergic neurons of the striatum and basal forebrain of patients with Alzheimer’s disease. Exp Neurol 145:245–252
Boissière F, Hunot S, Faucheux B, Hersh LB, Agid Y, Hirsch EC (1997) Trk neurotrophin receptors in cholinergic neurons of patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 8:1–8
Bolognini N, Russo C, Edwards DJ (2016) The sensory side of post-stroke motor rehabilitation. Restor Neurol Neurosci 38(4):385–393
Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurology 32:164–168
Bondareff W, Mountjoy CQ, Roth M, Rossor MN, Iversen LL, Reynolds GP, Hauser DL (1987) Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease. Alzheimer Dis Assoc Disord 1:256–262
Bouret S, Sara SJ (2002) Locus coeruleus activation modulates firing rate and temporal organization of odour-induced single-cell responses in rat piriform cortex. Eur J Neurosci 16:2371–2382
Bouret S, Sara SJ (2004) Reward expectation, orientation of attention and locus coeruleus-medial frontal cortex interplay during learning. Eur J Neurosci 20:791–802
Bouret S, Sara SJ (2005) Network reset: a simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci 28:574–582
Boutajangout A, Ingadottir J, Davies P, Sigurdsson EM (2011) Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 118:658–667
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 22:1030–1036
Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134
Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960–969
Braun C, Wilms A, Schweizer R, Godde B, Preissl H, Birbaumer N (2000) Activity patterns of human somatosensory cortex adapt dynamically to stimulus properties. NeuroReport 11:2977–29780
Brookmeyer R, Gray S, Kawas C (1998) Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88:1337–1342
Brown DR, Hunter R, Wyper DJ, Patterson J, Kelly RC, Montaldi D, McCullouch J (1996) Longitudinal changes in cognitive function and regional cerebral function in Alzheimer’s disease: a SPECT blood flow study. J Psychiatr Res 30:109–126
Brown RA, Walling SG, Milway JS, Harley CW (2005) Locus ceruleus activation suppresses feedforward interneurons and reduces beta-gamma electroencephalogram frequencies while it enhances theta frequencies in rat dentate gyrus. J Neurosci 25:1985–1991
Brueggen K, Dyrba M, Barkhof F, Hausner L, Filippi M, Nestor PJ, Hauenstein K, Klöppel S, Grothe MJ, Kasper E, Teipel SJ (2015) Basal forebrain and hippocampus as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment—a multicenter DTI and volumetry study. J Alzheimers Dis 48:197–204
Brunnström H, Friberg N, Lindberg E, Englund E (2011) Differential degeneration of the locus coeruleus in dementia subtypes. Clin Neuropathol 30:104–110
Buchman AS, Wilson RS, Boyle PA, Bienias JL, Bennett DA (2007) Grip strength and the risk of incident Alzheimer’s disease. Neuroepidemiology 29:66–73
Buckner RL (2004) Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44:195–208
Burk JA, Herzog CD, Porter MC, Sarter M (2002) Interactions between aging and cortical cholinergic deafferentation on attention. Neurobiol Aging 23:467–477
Burke MA, Mobley WC, Cho J, Wiegand SJ, Lindsay RM, Mufson EJ, Kordower JH (1994) Loss of developing cholinergic basal forebrain neurons following excitotoxic lesions of the hippocampus: rescue by neurotrophins. Exp Neurol 130:178–195
Burt AM (1992) Text book of neuroanatomy. ISBN 0-7216-4899-1, W. B. Saunders Co., Philadelphia
Burton H, Sinclair RJ (2000) Attending to and remembering tactile stimuli: a review of brain imaging data and single-neuron responses. J Clin Neurophysiol 17:575–591
Burton H, Videen TO, Raichle ME (1993) Tactile-vibration-activated foci in insular and parietal-opercular cortex studied with positron emission tomography: mapping the second somatosensory area in humans. Somatosens Mot Res 10:297–308
Burton H, Abend NS, MacLeod AM, Sinclair RJ, Snyder AZ, Raichle ME (1999) Tactile attention tasks enhance activation in somatosensory regions of parietal cortex: a positron emission tomography study. Cereb Cortex 9:662–674
Burwell RD, Amaral DG (1998) Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat. J Comp Neurol 398:179–205
Butt AE, Chavez CM, Flesher MM, Kinney-Hurd BL, Araujo GC, Miasnikov AA, Weinberger NM (2009) Association learning-dependent increases in acetylcholine release in the rat auditory cortex during auditory classical conditioning. Neurobiol Learn Mem 92:400–409
Cai S, Huang L, Zou J, Jing L, Zhai B, Ji G, von Deneen KM, Ren J, Ren A (2015) Changes in thalamic connectivity in the early and late stages of amnestic mild cognitive impairment: a resting-state functional magnetic resonance study from ADNI. PLoS One 10:e0115573
Cao WH, Sato A, Sato Y, Zhou W (1992) Somatosensory regulation of regional hippocampal blood flow in anesthetized rats. Jpn J Physiol 42:731–740
Caplan DJ, Weintraub JA (1993) The oral health burden in the United States: a summary of recent epidemiologic studies. J Dent Educ 57:853–862
Carmignoto G, Gomez-Gonzalo M (2010) The contribution of astrocyte signalling to neurovascular coupling. Brain Res Rev 63:138–148
Carta A, Calvani M, Bravi D, Bhuachalla SN (1993) Acetyl-l-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere. Ann N Y Acad Sci 695:324–326
Carter ME, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S, Deisseroth K, de Lecea L (2010) Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci 13:1526–1533
Casamenti F, Scali C, Giovannelli L, Faussone-Pellegrini MS, Pepeu G (1994) Effect of nerve growth factor and GM1 ganglioside on the recovery of cholinergic neurons after a lesion of the nucleus basalis in aging rats. J Neural Transm Park Dis Dement Sect 7:177–193
Celle S, Peyron R, Faillenot I, Pichot V, Alabdullah M, Gaspoz JM, Laurent B, Barthélémy JC, Roche F (2009) Undiagnosed sleep-related breathing disorders are associated with focal brainstem atrophy in the elderly. Hum Brain Mapp 30:2090–2097
Chai X, Wu S, Murray TK, Kinley R, Cella CV, Sims H, Buckner N, Hanmer J, Davies P, O’Neill MJ, Hutton ML, Citron M (2011) Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression. J Biol Chem 286:34457–34467
Chalermpalanupap T, Kinkead B, Hu WT, Kummer MP, Hammerschmidt T, Heneka MT, Weinshenker D, Levey AI (2013) Targeting norepinephrine in mild cognitive impairment and Alzheimer’s disease. Alzheimers Res Ther 5:21
Chamberlain SR, Robbins TW (2013) Noradrenergic modulation of cognition: therapeutic implications. J Psychopharmacol 27:694–718
Chan E, Steenland HW, Liu H, Horner RL (2006) Endogenous excitatory drive modulating respiratory muscle activity across sleep-wake states. Am J Respir Crit Care Med 174:1264–1273
Chang JY, Liu LZ (2000) Catecholamines inhibit microglial nitric oxide production. Brain Res Bull 52:525–530
Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson’s disease with and without dementia and depression. J Comp Neurol 287:373–392
Chetelat G, Desgranges B, de la Sayette V, Viader F, Berkouk K, Landeau B, Lalevée C, Le Doze F, Dupuy B, Hannequin D, Baron JC, Eustache F (2003) Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain 126:1955–1967
Chételat G, Eustache F, Viader F, De La Sayette V, Pélerin A, Mézenge F, Hannequin D, Dupuy B, Baron JC, Desgranges B (2005) FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment. Neurocase 11:14–25
Chiang C, Aston-Jones G (1993) Response of locus coeruleus neurons to footshock stimulation is mediated by neurons in the rostral ventral medulla. Neuroscience 53:705–715
Chien W, Lin FR (2012) Prevalence of hearing aid use among older adults in the United States. Arch Intern Med 172:292–293
Cirelli C, Faraguna U, Tononi G (2006) Changes in brain gene expression after long-term sleep deprivation. J Neurochem 98:1632–1645
Claassen JAHR, Jansen RWMM (2006) Cholinergically mediated augmentation of cerebral perfusion in Alzheimer’s disease and related cognitive disorders: the cholinergic–vascular hypothesis. J Gerontol (Series A: Biol Sci and Med Sci) 61:267–271
Clarke DJ, Gage FH, Nilsson OG, Björklund A (1986) Grafted septal neurons form cholinergic synaptic connections in the dentate gyrus of behaviorally impaired aged rats. J Comp Neurol 252:483–492
Cleland TA (2014) Construction of odor representations by olfactory bulb microcircuits. Prog Brain Res 208:177–203
Cohen TE, Kaplan SW, Kandel ER, Hawkins RD (1997) A simplified preparation for relating cellular events to behavior: mechanisms contributing to habituation, dishabituation, and sensitization of the Aplysia gill-withdrawal reflex. J Neurosci 17:2886–2899
Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ (2002) Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor downregulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 70:462–473
Collier B, Mitchell JF (1966) The central release of acetylcholine during stimulation of the visual pathway. J Physiol 184:239–254
Corbetta M, Patel G, Shulman GL (2008) The reorienting system of the human brain: from environment to theory of mind. Neuron 58:306–324
Coull JT (1994) Pharmacological manipulations of the alpha 2-noradrenergic system. Effects on cognition. Drugs Aging 5:116–126
Counts SE, Mufson EJ (2005) The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease. J Neuropathol Exp Neurol 64:263–272
Counts SE, Mufson EJ (2010) Noradrenaline activation of neurotrophic pathways protects against neuronal amyloid toxicity. J Neurochem 113:649–660
Cox SB, Woolsey TA, Rovainen CM (1993) Localized dynamic changes in cortical blood flow with whisker stimulation corresponds to matched vascular and neuronal architecture of rat barrels. J Cereb Blood Flow Metab 13:899–913
Craft S (2007) Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 4:147–152
Crawford F, Suo Z, Fang C, Mullan M (1998) Characteristics of the in vitro vasoactivity of beta-amyloid peptides. Exp Neurol 150:159–168
Crouzin N, Baranger K, Cavalier M, Marchalant Y, Cohen-Solal C, Roman FS, Khrestchatisky M, Rivera S, Féron F, Vignes M (2013) Area-specific alterations of synaptic plasticity in the 5XFAD mouse model of Alzheimer’s disease: dissociation between somatosensory cortex and hippocampus. PLoS One 8:e74667
Crowe DA, Goodwin SJ, Blackman RK, Sakellaridi S, Sponheim SR, MacDonald AW 3rd, Chafee MV (2013) Prefrontal neurons transmit signals to parietal neurons that reflect executive control of cognition. Nat Neurosci 16:1484–1491
Cui JG, Hill JM, Zhao Y, Lukiw WJ (2007) Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer’s disease. NeuroReport 18:115–119
Cullinan WE, Zaborszky L (1991) Organization of ascending hypothalamic projections to the rostral forebrain with special reference to the innervation of cholinergic projection neurons. J Comp Neurol 306:631–667
Culmsee C, Semkova I, Krieglstein J (1999a) NGF mediates the neuroprotective effect of the b2-adrenoceptor agonist clenbuterol in vitro and in vivo: evidence from an NGF-antisense study. Neurochem Int 35:47–57
Culmsee C, Stumm RK, Schäfer MK, Weihe E, Krieglstein J (1999b) Clenbuterol induces growth factor mRNA, activates astrocytes, and protects rat brain tissue against ischemic damage. Eur J Pharmacol 379:33–45
Cummings JL, Back C (1988) The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiat 6:S64–S78
Daselaar SM, Fleck MS, Cabeza R (2006) Triple dissociation in the medial temporal lobes: recollection, familiarity, and novelty. J Neurophysiol 96:1902–1911
Daulatzai MA (2010) Early stages of pathogenesis in memory impairment during normal senescence and alzheimer’s disease. J Alzheimers Dis 20:355–367
Daulatzai MA (2011) Role of sensory stimulation in amelioration of obstructive sleep apnea. Sleep Disord. 2011(2011):596879
Daulatzai MA (2012a) Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer’s disease. Neurochem Res 37:2627–2658
Daulatzai MA (2012b) Dysfunctional nucleus tractus solitarius: its crucial role in promoting neuropathogenetic cascade of Alzheimer’s dementia–a novel hypothesis. Neurochem Res 37:846–868
Daulatzai MA (2013a) Neurotoxic saboteurs: straws that break the hippo’s (hippocampus) back drive cognitive impairment and Alzheimer’s disease. Neurotox Res 24:407–459
Daulatzai MA (2013b) Death by a thousand cuts in Alzheimer’s disease: hypoxia—the prodrome. Neurotox Res 24:216–243
Daulatzai M (2014) Role of stress, depression, and aging in cognitive decline and Alzheimer’s disease. Curr Top Behav Neurosci 18:265–296
Daulatzai MA (2015a) Olfactory dysfunction: its early temporal relationship and neural correlates in the pathogenesis of Alzheimer’s disease. J Neural Transm (Vienna) 122:1475–1497
Daulatzai MA (2015b) Evidence of neurodegeneration in obstructive sleep apnea: relationship between obstructive sleep apnea and cognitive dysfunction in the elderly. J Neurosci Res 93:1778–1794
Daulatzai MA (2016a) Pharmacotherpy and Alzheimer’s disease: the M-drugs (melatonin, minocycline, modafinil, and memantine) approach. Curr Pharm Des 22:2411–2430
Daulatzai MA (2016b) Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease, in press
Daulatzai MA (2016c) Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer’s disease. Am J Neurodegener Dis 5:1–28
Daulatzai MA (2016d) Aging—calm before the storm of cognitive impairment: protective effect of beneficial anti-aging strategies, in press
Dauvergne C, Pinganaud G, Buisseret P, Buisseret-Delmas C, Zerari-Mailly F (2001) Neurosci Lett 311:109–112
Dayan P, Yu AJ (2006) Phasic norepinephrine: a neural interrupt signal for unexpected events. Network 17:335–350
De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Klein WL (2007) Aβ oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282:11590–11601
De Visser A, Hemming A, Yang C, Zaver S, Dhaliwal R, Jawed Z, Toth C (2014) The adjuvant effect of hypertension upon diabetic peripheral neuropathy in experimental type 2 diabetes. Neurobiol Dis 62:18–30
Debette S, Seshadri S, Beiser A, Au R, Himali JJ, Palumbo C, Decarli C (2011) Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology 77:461–468
DeCarli C (2013) Clinically asymptomatic vascular brain injury: a potent cause of cognitive impairment among older individuals. J Alzheimers Dis 33:S417–S426
DeCarli C, Murphy DG, Tranh M, Grady CL, Haxby JV, Gillette JA, Salerno JA, Gonzales-Aviles A, Horwitz B, Rapoport SI et al (1995) The effect of white matter hyper intensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology 45:2077–2084
Détári L, Semba K, Rasmusson DD (2006) Responses of cortical EEG-related basal forebrain neurons to brainstem and sensory stimulation in urethane-anaesthetized rats. Eur J Neurosci 9:1153–1161
deToledo-Morrell L, Stoub TR, Wang C (2007) Hippocampal atrophy and disconnection in incipient and mild Alzheimer’s disease. Prog Brain Res 163:741–753
Devanand DP, Michaels-Marston KS, Liu X, Pelton GH, Padilla M, Marder K, Bell K, Stern Y, Mayeux R (2000) Olfactory deficits in patients with mild cognitive impairment predict Alzheimer’s disease at follow-up. Am J Psychiatry 157:1399–1405
Devilbiss DM, Waterhouse BD (2000) Norepinephrine exhibits two distinct profiles of action on sensory cortical neuron responses to excitatory synaptic stimuli. Synapse 37:273–282
Devilbiss DM, Waterhouse BD (2004) The effects of tonic locus ceruleus output on sensory-evoked responses of ventral posterior medial thalamic and barrel field cortical neurons in the awake rat. J Neurosci 24:10773–10785
Devilbiss DM, Page ME, Waterhouse BD (2006) Locus ceruleus regulates sensory encoding by neurons and networks in waking animals. J Neurosci 26:9860–9872
Dickey C, Kraft C, Jinwal U, Koren J, Johnson A, Anderson L, Lebson L, Lee D, Dickson D, de Silva R, Binder LI, Morgan D, Lewis J (2009) Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy. Am J Pathol 174:228–238
Dietrich WD, Ginsberg MD, Busto R, Smith DW (1985) Metabolic alterations in rat somatosensory cortex following unilateral vibrissal removal. J Neurosci 5:874–880
Dik MG, Jonker C, Comijs HC, Deeg DJ, Kok A, Yaffe K, Penninx BW (2007) Contribution of metabolic syndrome components to cognition in older individuals. Diabetes Care 30:2655–2660
Donoghue JP, Carroll KL (1987) Cholinergic modulation of sensory responses in rat primary somatic sensory cortex. Brain Res 408:367–371
Doucette W, Milder J, Restrepo D (2007) Adrenergic modulation of olfactory bulb circuitry affects odor discrimination. Learn Mem 14:539–547
Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, Schwaiger M, Kurz A (2003) Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 30:1104–1113
Du AT, Schuff N, Kramer JH, Ganzer S, Zhu XP, Jagust WJ, Miller BL, Reed BR, Mungas D, Yaffe K, Chui HC, Weiner MW (2004) Higher atrophy rate of entorhinal cortex than hippocampus in AD. Neurology 62:422–427
Dunn W, Griffith JW, Sabata D, Morrison MT, MacDermid JC, Darragh A, Schaaf R, Dudgeon B, Connor LT, Carey L, Tanquary J (2015) Measuring change in somatosensation across the lifespan. Am J Occup Ther 69:6903290020p1–6903290020p9
Dupuis K, Pichora-Fuller MK, Chasteen AL, Marchuk V, Singh G, Smith SL (2015) Effects of hearing and vision impairments on the Montreal Cognitive Assessment. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 22:413–437
Eckmeier D, Shea SD (2014) Noradrenergic plasticity of olfactory sensory neuron inputs to the main olfactory bulb. J Neurosci 34:15234–15243
Edvinsson L, MacKenzie ET, McCulloch J (1993) Cerebral blood flow and metabolism. Raven, New York, pp 92–110
Eggermann E, Kremer Y, Crochet S, Petersen CC (2014) Cholinergic signals in mouse barrel cortex during active whisker sensing. Cell Rep 9:1654–1660
Encinas M, De Juan R, Marcos A, Gil P, Barabash A, Fernandez C, De Ugarte C, Cabranes JA (2003) Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer’s disease. Eur J Nucl Med Mol Imaging 30:1473–1480
Ennis M, Aston-Jones G (1988) Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain. J Neurosci 8:3644–3657
Enright PL, Newman AB, Wahl PW, Manolio TA, Haponik EF, Boyle PJ (1996) Prevalence and correlates of snoring and observed apneas in 5,201 older adults. Sleep 19:531–538
Enriquez K, Lehrer E, Mullol J (2014) The optimal evaluation and management of patients with a gradual onset of olfactory loss. Curr Opin Otolaryngol Head Neck Surg 22:34–41
España RA, Berridge CW (2006) Organization of noradrenergic efferents to arousal-related basal forebrain structures. J Comp Neurol 496:668–683
Feinstein DL (1998) Suppression of astroglial nitric oxide synthase expression by norepinephrine results from decreased NOS-2 promoter activity. J Neurochem 70:1484–1496
Feinstein DL, Heneka MT, Gavrilyuk V, Dello Russo C, Weinberg G, Galea E (2002) Noradrenergic regulation of inflammatory gene expression in brain. Neurochem Int 41:357–365
Fenik VB, Davies RO, Kubin L (2005) Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep-like depression of hypoglossal motoneuronal activity. J Sleep Res 14:419–429
Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM (2016) Alzheimer’s disease: targeting the cholinergic system. Curr Neuropharmacol 14:101–115
Figlewicz DP, Brot MD, McCall AL, Szot P (1996) Diabetes causes differential changes in CNS noradrenergic and dopaminergic neurons in the rat: a molecular study. Brain Res 736:54–60
Fischer ME, Cruickshanks KJ, Wiley TL, Klein BE, Klein R, Tweed TS (2011) Determinants of hearing aid acquisition in older adults. Am J Public Health 101:1449–1455
Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S (2005) Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol 62:1539–1544
Fjell AM, Westlye LT, Grydeland H, Amlien I, Espeseth T, Reinvang I (2013) Alzheimer disease neuroimaging. I. Critical ages in the life course of the adult brain: nonlinear subcortical aging. Neurobiol Aging 34:2239–2247
Fjell AM, Westlye LT, Grydeland H, Amlien I, Espeseth T, Reinvang I (2014) Alzheimer Disease Neuroimaging, I. Accelerating cortical thinning: unique to dementia or universal in aging? Cereb Cortex 24:919–934
Fleiner F, Lau L, Göktas Ö (2012) Active olfactory training for the treatment of smelling disorders. Ear Nose Throat J 91:198–203
Florin-Lechner SM, Druhan JP, Aston-Jones G, Valentino RJ (1996) Enhanced norepinephrine release in prefrontal cortex with burst stimulation of the locus coeruleus. Brain Res 742:89–97
Flück D, Beaudin AE, Steinback CD, Kumarpillai G, Shobha N, McCreary CR, Peca S, Smith EE, Poulin MJ (2014) Effects of aging on the association between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness. Front Physiol. 5:49
Foote SL, Aston-Jones G, Bloom FE (1980) Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc Natl Acad Sci USA 77:3033–3037
Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63:844–914
Fornai F, di Poggio AB, Pellegrini A, Ruggieri S, Paparelli A (2007) Noradrenaline in Parkinson’s disease: from disease progression to current therapeutics. Curr Med Chem 14:2330–2334
Forno LS (1992) Neuropathologic features of Parkinson’s, Huntington’s, and Alzheimer’s diseases. Ann NY Acad Sci 648:6–16
Forstl H, Levy R, Burns A, Luthert P, Cairns N (1994) Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer’s disease—a hypothesis. Pharmacopsychiatry 27:11–15
Fournier GN, Semba K, Rasmusson DD (2004) Modality- and region-specific acetylcholine release in the rat neocortex. Neuroscience 126:257–262
Fox PT, Burton H, Raichle ME (1987) Mapping human somatosensory cortex with positron emission tomography. J Neurosurg 67:34–43
Frangos E, Ellrich J, Komisaruk BR (2015) Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul 8:624–636
Freddi R, Duca P, Gritti I, Mariotti M, Vertemati M (2009) Behavioral and degeneration changes in the basal forebrain systems of aged rats: a quantitative study in the region of the basal forebrain after levo-acetyl-carnitine treatments assessed by Abercrombie estimation. Prog Neuropsychopharmacol Biol Psychiatry 33:419–426
Freedman R, Foote SL, Bloom FE (1975) Histochemical characterization of a neocortical projection of the nucleus locus coeruleus in the squirrel monkey. J Comp Neurol 164:209–231
Freo U, Dam M, Ori C (2009) Cerebral metabolic effects of acetyl-l-carnitine in rats during aging. Brain Res 1259:32–39
Friberg D (1999) Heavy snorer’s disease: a progressive local neuropathy. Acta Otolaryngol 119:925–933
Friberg D, Gazelius B, Hökfelt T, Nordlander B (1997) Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers. Regul Pept 71:29–36
Fried K (1992) Changes in pulpal nerves with aging. Proc Finn Dent Soc 88:517–528
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 13:5–14
Frohman EM, Vayuvegula B, van den NS, Gupta S (1988) Norepinephrine inhibits gamma-interferon-induced MHC class II (Ia) antigen expression on cultured brain astrocytes. J Neuroimmunol 17:89–101
Fukuyama H, Ouchi Y, Matsuzaki S, Ogawa M, Yamauchi H, Nagahama Y, Kimura J, Yonekura Y, Shibasaki H, Tsukada H (1996) Focal cortical blood flow activation is regulated by intrinsic cortical cholinergic neurons. Neuroimage 3:195–201
Fure S, Zickert I (1997) Incidence of tooth loss and dental caries in 60-, 70- and 80-year-old Swedish individuals. Community Dent Oral Epidemiol 25:137–142
Gabbita SP, Srivastava MK, Eslami P, Johnson MF, Kobritz NK, Tweedie D, Greig NH, Zemlan FP, Sharma SP, Harris-White ME (2012) Early intervention with a small molecule inhibitor for tumor necrosis factor-α prevents cognitive deficits in a triple transgenic mouse model of Alzheimer’s disease. J Neuroinflammation 9:99
Gais S, Born J (2004) Declarative memory consolidation: mechanisms acting during human sleep. Learn Mem 11:679–685
Gais S, Rasch B, Dahmen JC, Sara S, Born J (2011) The Memory Function of Noradrenergic Activity in Non-REM Sleep. J Cogn Neurosci 23:2582–2592
Galea E, Feinstein DL (1999) Regulation of the expression of the inflammatory nitric oxide synthase (NOS2) by cyclic AMP. FASEB J 13:2125–2137
Gates GA, Karzon RK, Garcia P, Peterein J, Storandt M, Morris JC, Miller JP (1995) Auditory dysfunction in aging and senile dementia of the Alzheimer’s type. Arch Neurol 52:626–634
Gates GA, Cobb JL, Linn RT, Rees T, Wolf PA, D’Agostino RB (1996) Central auditory dysfunction, cognitive dysfunction, and dementia in older people. Arch Otolaryngol Head Neck Surg 122:161–167
Gates GA, Beiser A, Rees TS, D’Agostino RB, Wolf PA (2002) Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer’s disease. J Am Geriatr Soc 50:482–488
Gates GA, Anderson ML, Feeney MP, McCurry SM, Larson EB (2008) Central auditory dysfunction in older persons with memory impairment or Alzheimer dementia. Arch Otolaryngol Head Neck Surg 134:771–777
Gavriely N, Jensen OE (1993) Theory and measurement of snores. J Appl Physiol 74:2828–2837
Gaykema RP, van Weeghel R, Hersh LB, Luiten PG (1991) Prefrontal cortical projections to the cholinergic neurons in the basal forebrain. J Comp Neurol 303:563–583
Gebicke-Haerter PJ (2001) Microglia in neurodegeneration: molecular aspects. Microsc Res Tech 54:47–58
George MJ (1992) Modification of receptive fields of posteriomedial barrel subfield neocortical single units by known concentrations of iontophoresed noradrenaline in the rat. Int J Neurosci 65:69–81
Gerhard A, Trender-Gerhard I, Turkheimer F, Quinn NP, Bhatia KP, Brooks DJ (2006) In vivo imaging of microglial activation with [11C] (R)-PK11195 PET in progressive supranuclear palsy. Mov Disord 21:89–93
German DC, Manaye KF, White CL III, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DM (1992) Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32:667–676
German DC, Yazdani U, Speciale SG, Pasbakhsh P, Games D, Liang CL (2003) Cholinergic neuropathology in a mouse model of Alzheimer’s disease. J Comp Neurol 462:371–381
German DC, Nelson O, Liang F, Liang CL, Games D (2005) The PDAPP mouse model of Alzheimer’s disease: locus coeruleus neuronal shrinkage. J Comp Neurol 492:469–476
Gerrits RJ, Raczynski C, Greene AS, Stein EA (2000) Regional cerebral blood flow responses to variable frequency whisker stimulation: an autoradiographic analysis. Brain Res 864:205–212
Ghazanfar AA, Stambaugh CR, Nicolelis MA (2000) Encoding of tactile stimulus location by somatosensory thalamocortical ensembles. J Neurosci 20:3761–3775
Ghosal K, Vogt DL, Liang M, Shen Y, Lamb BT, Sanjay W, Pimplikara SW (2009) Alzheimer’s diseaselike pathological features in transgenic mice expressing the APP intracellular domain. Proc Natl Acad Sci USA 106:18367–18372
Ghosh S, Wu MD, Shaftel SS, Kyrkanides S, LaFerla FM, Olschowka JA, O’Banion MK (2013) Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. J Neurosci 33:5053–5064
Gibson GE, Peterson C (1981) Aging decreases oxidative metabolism and the release and synthesis of acetylcholine. J Neurochem 37:978–984
Ginsberg MD, Dietrich WD, Busto R (1987) Coupled forebrain increases of local cerebral glucose utilization and blood flow during physiologic stimulation of a somatosensory pathway in the rat: demonstration by double-label autoradiography. Neurology 37:11–19
Gleeson LC, Ryan KJ, Griffin EW, Connor TJ, Harkin A (2010) The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. Brain Behav Immun 24:1354–1361
Gnatkovsky V, Uva L, de Curtis M (2004) Topographic distribution of direct and hippocampus- mediated entorhinal cortex activity evoked by olfactory tract stimulation. Eur J Neurosci 20:1897–1905
Goadsby PJ (1989) Effect of stimulation of facial nerve on regional cerebral blood flow and glucose utilization in cats. Am J Physiol 257:R517–R521
Godefroy O, Azouvi P, Robert P, Roussel M, LeGall D, Meulemans T (2010) Dysexecutive syndrome: diagnostic criteria and validation study. Ann Neurol 68:855–864
Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16:460–465
Goekoop R, Scheltens P, Barkhof F, Rombouts SA (2006) Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study. Brain 129:141–157
Golmayo L, Nuñez A, Zaborszky L (2003) Electrophysiological evidence for the existence of a posterior cortical-prefrontal-basal forebrain circuitry in modulating sensory responses in visual and somatosensory rat cortical areas. Neuroscience 119:597–609
Gomez Isla T, Price JL, McKeel DW Jr, Morris JC, Growdon JH, Hyman BT (1996) Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J Neurosci 16:4491–4500
Gonzaga C, Bertolami A, Bertolami M, Amodeo C, Calhoun D (2015) Obstructive sleep apnea, hypertension and cardiovascular diseases. J Hum Hypertens 29:705–712
Grady CL, Maisog JM, Horwitz B, Ungerleider LG, Mentis MJ, Salerno JA, Pietrini P, Wagner E, Haxby JV (1994) Age-related changes in cortical blood flow activation during visual processing of faces and location. J Neurosci 14:1450–1462
Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI (2001) Altered brain functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain 124:739–756
Gregory JA, Jolivalt CG, Goor J, Mizisin AP, Calcutt NA (2012) Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats. Acta Neuropathol 124:561–573
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642
Gröschel S, Sohns JM, Schmidt-Samoa C, Baudewig J, Becker L, Dechent P, Kastrup A (2013) Effects of age on negative BOLD signal changes in the primary somatosensory cortex. Neuroimage 71:10–18
Grothe M, Heinsen H, Teipel S (2013) Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer’s disease. Neurobiol Aging 34:1210–1220
Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 28:327–335
Gudziol V, Pietsch J, Witt M, Hummel T (2010) Theophylline induces changes in the electro-olfactogram of the mouse. Eur Arch Otorhinolaryngol 267:239–243
Guérin D, Sacquet J, Mandairon N, Jourdan F, Didier A (2009) Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol Aging 30:272–283
Gulturk S, Gedik R, Develioglu H, Oztoprak I, Cetin A (2009) Assessment of the outcomes of cerebral blood flow measurements after electrical stimulation of upper right incisor tooth in rabbits. Int J Neurosci 119:1292–1302
Guo L, Duggan J, Cordeiro MF (2010) Alzheimer’s disease and retinal neurodegeneration. Curr Alzheimer Res 7:3–14
Gustafson D (2006) Adiposity indices and dementia. Lancet Neurol 5:713–720
Haglund M, Sjöbeck M, Englund E (2006) Locus ceruleus degeneration is ubiquitous in Alzheimer’s disease: possible implications for diagnosis and treatment. Neuropathology 26:528–532
Hanamori T, Kunitake T, Kato K, Kannan H (1998) Responses of neurons in the insular cortex to gustatory, visceral, and nociceptive stimuli in rats. J Neurophysiol 79:2535–2545
Hanyu H, Sato T, Hirao K, Kanetaka H, Iwamoto T, Koizumi K (2010) The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer’s disease: a longitudinal SPECT study. J Neurol Sci 290:96–101
Harley C (1991) Noradrenergic and locus coeruleus modulation of the perforant path-evoked potential in rat dentate gyrus supports a role for the locus coeruleus in attentional and memorial processes. Prog Brain Res 88:307–321
Harley CW (2007) Norepinephrine and the dentate gyrus. Prog Brain Res 163:299–318
Hasegawa M, Hada J, Abe T, Honda K, Shimizu A, Urade M (2009) Theophylline attenuates hippocampal blood flow responses induced by tooth pulp stimulation in rats. Neurosci Res 65:156–159
Hasselmo ME (1999a) Neuromodulation: acetylcholine and memory consolidation. Trends Cogn Sci 3:351–359
Hasselmo ME (1999b) Neuromodulation and the hippocampus: memory function and dysfunction in a network simulation. Prog Brain Res 121:3–18
Hasselmo ME (2005) What is the function of hippocampal theta rhythm?–Linking behavioral data to phasic properties of field potential and unit recording data. Hippocampus 15:936–949
Hasselmo ME (2006) The role of acetylcholine in learning and memory. Curr Opin Neurobiol 16:710–715
Hasselmo ME, Giocomo LM (2006) Cholinergic modulation of cortical function. J Mol Neurosci 30:133–135
Hawkins RD, Greene W, Kandel ER (1998) Classical conditioning, differential conditioning, and second-order conditioning of the Aplysia gill-withdrawal reflex in a simplified mantle organ preparation. Behav Neurosci 112:636–645
Hays SA (2016) Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Neurotherapeutics 13:382–394
He Y, Zhu J, Huang F, Qin L, Fan W, He H (2014) Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage. Neural Regen Res 9:1985–1994
Head D, Rodrigue KM, Kennedy KM, Raz N (2008) Neuroanatomical and cognitive mediators of age-related differences in episodic memory. Neuropsychology 22:491–507
Hellings PW, Rombaux P (2009) Medical therapy and smell dysfunction. B-ENT 5:71–75
Helman AM, Murphy MP (2015) Vascular cognitive impairment: modeling a critical neurologic disease in vitro and in vivo. Biochim Biophys Acta 2015. doi:10.1016/j.bbadis.2015.12.009
Hemsworth BA, Mitchell JF (1969) The characteristics of acetylcholine release mechanisms in the auditory cortex. Br J Pharmacol 36:161–170
Heneka MT, Galea E, Gavriluyk V, Dumitrescu-Ozimek L, Daeschner J, O’Banion MK, Weinberg G, Klockgether T, Feinstein DL (2002) Noradrenergic depletion potentiates beta -amyloid-induced cortical inflammation: implications for Alzheimer’s disease. J Neurosci 22:2434–2442
Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, Sastre M, Galldiks N, Zimmer A, Hoehn M, Heiss WD, Klockgether T, Staufenbiel M (2006) Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J Neurosci 26:1343–1354
Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, Hanisch UK, Kummer MP (2010) Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci USA 107:6058–6063
Herholz K, Weisenbach S, Kalbe E (2008) Deficits of the cholinergic system in early AD. Neuropsychologia 46:1642–1647
Herrera-Rincon C, Panetsos F (2014) Substitution of natural sensory input by artificial neurostimulation of an amputated trigeminal nerve does not prevent the degeneration of basal forebrain cholinergic circuits projecting to the somatosensory cortex. Front Cell Neurosci 8:385
Hirao K, Ohnishi T, Matsuda H, Nemoto K, Hirata Y, Yamashita F, Asada T, Iwamoto T (2006) Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer’s disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun 27:151–156
Holdefer RN, Jacobs BL (1994) Phasic stimulation of the locus coeruleus: effects on activity in the lateral geniculate nucleus. Exp Brain Res 100:444–452
Hoozemans JJM, van Haastert ES, Nijholt DAT, Rozemuller AJM, Eikelenboom P, Scheper W (2009) The unfolded protein response is activated in pretangle neurons in Alzheimer’s disease hippocampus. Am J Pathol 174:1241–1251
Horwitz B (1994) Data analysis paradigms for metabolic-flow data: combining neural modeling and functional neuroimaging. Hum Brain Mapp 2:112–122
Hosoi M, Hori K, Konishi K, Tani M, Tomioka H, Kitajima Y, Akashi N, Inamoto A, Kurosawa K, Yuda H, Hanashi T, Ouchi H, Hachisu M (2015) Pharmacotherapy for neurocognitive disorders based on the hypothesis of endogenous appearance of anticholinergic activity. Neurodegener Dis 15:157–161
Hotta H, Uchida S, Kagitani F, Maruyama N (2011) Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice. J Physiol Sci 61:201–209
Hua T, Li X, He L, Zhou Y, Wang Y, Leventhal AG (2006) Functional degradation of visual cortical cells in old cats. Neurobiol Aging 27:155–162
Huang L, Quinn SJ, Ellis PDM, Ffowcs Williams JE (1995) Biomechanics of snoring. Endeavour 19:96–100
Husner A, Frasnelli J, Welge-Lüssen A, Reiss G, Zahnert T, Hummel T (2006) Loss of trigeminal sensitivity reduces olfactory function. Laryngoscope 116:1520–1522
Hutchison JL, Lu H, Rypma B (2013) Neural mechanisms of age-related slowing: the ΔCBF/ΔCMRO2 ratio mediates age-differences in BOLD signal and human performance. Cereb Cortex 23:2337–2346
Iadecola C (1993) Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? Trends Neurosci 16:206–214
Iadecola C, Zhang F, Niwa K, Eckman C, Turner SK, Fischer E, Younkin S, Borchelt DR, Hsiao KK, Carlson GA (1999) SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 2:157–161
Idrizbegovic E, Hederstierna C, Dahlquist M, Rosenhall U (2013) Short-term longitudinal study of central auditory function in Alzheimer’s disease and mild cognitive impairment. Dement Geriatr Cogn Dis Extra 3:468–471
Ikeda M, Shoji M, Kawarai T, Kawarabayashi T, Matsubara E, Murakami T, Sasaki A, Tomidokoro Y, Ikarashi Y, Kuribara H, Ishiguro K, Hasegawa M, Yen SH, Chishti MA, Harigaya Y, Abe K, Okamoto K, St George-Hyslop P, Westaway D (2005) Accumulation of filamentous tau in the cerebral cortex of human tau R406 W transgenic mice. Am J Pathol 166:521–531
Ikonomovic MD, Mufson EJ, Wu J, Cochran EJ, Bennett DA, DeKosky ST (2003) Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer’s neuropathology. J Alzheimers Dis 5:39–48
Inglis FM, Fibiger HC (1995) Increases in hippocampal and frontal cortical acetylcholine release associated with presentation of sensory stimuli. Neuroscience 66:81–86
Iravani MM, Sadeghian M, Rose S, Jenner P (2014) Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss. J Neural Transm (Vienna) 121:1493–1505
Irle E, Markowitsch HJ (1986) Afferent connections of the substantia innominata/basal nucleus of Meynert in carnivores and primates. J Hirnforsch 27:343–367
Ishida Y, Shirokawa T, Miyaishi O, Komatsu Y, Isobe K (2000) Age-dependent changes in projections from locus coeruleus to hippocampus dentate gyrus and frontal cortex. Eur J Neurosci 12:1263–1270
Ishida Y, Shirokawa T, Miyaishi O, Komatsu Y, Isobe K (2001) Age-dependent changes in noradrenergic innervations of the frontal cortex in F344 rats. Neurobiol Aging 22:283–286
Ishizawa K, Dickson DW (2001) Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration. J Neuropathol Exp Neurol 60:647–657
Iversen LL, Rossor MN, Reynolds GP, Hills R, Roth M, Mountjoy CQ, Foote SL, Morrison JH, Bloom FE (1983) Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer’s type. Neurosci Lett 39:95–100
Iwamoto K, Mata D, Linn DM, Linn CL (2013a) Neuroprotection of rat retinal ganglion cells mediated through alpha7 nicotinic acetylcholine receptors. Neuroscience 237:184–198
Iwamoto T, Hanyu H, Umahara T (2013b) Age-related changes of sensory system. Nihon Rinsho 71:1720–1725
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Trojanowski JQ (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216
Jacobs SE, Juliano SL (1995) The impact of basal forebrain lesions on the ability of rats to perform a sensory discrimination task involving barrel cortex. J Neurosci 15:1099–1109
Jagust WJ, Eberling JL, Richardson BC, Reed BR, Baker MG, Nordahl TE, Budinger TF (1993) The cortical topography of temporal lobe hypometabolism in early Alzheimer’s disease. Brain Res 629:189–198
Janik R, Thomason LA, Chaudhary S, Dorr A, Scouten A, Schwindt G, Masellis M, Stanisz GJ, Black SE, Stefanovic B (2015) Attenuation of functional hyperemia to visual stimulation in mild Alzheimer’s disease and its sensitivity to cholinesterase inhibition. Biochim Biophys Acta. doi:10.1016/j.bbadis.2015.10.023
Jardanhazi-Kurutz D, Kummer MP, Terwel D, Vogel K, Dyrks T, Thiele A, Heneka MT (2010) Induced LC degeneration in APP/PS1 transgenic mice accelerates early cerebral amyloidosis and cognitive deficits. Neurochem Int 57:375–382
Jardanhazi-Kurutz D, Kummer MP, Terwel D, Vogel K, Thiele A, Heneka MT (2011) Distinct adrenergic system changes and neuroinflammation in response to induced locus ceruleus degeneration in APP/PS1 transgenic mice. Neuroscience 176:396–407
Jaworski T, Lechat B, Demedts D, Gielis L, Devijver H, Borghgraef P, Duimel H, Verheyen F, Kügler S, Van Leuven F (2011) Dendritic degeneration, neurovascular defects, and inflammation precede neuronal loss in a mouse model for tau-mediated neurodegeneration. Am J Pathol 179:2001–2015
Jean A (1984) Brainstem organization of the swallowing network. Brain Behav Evol 25:109–116
Jiang Y, Li L, Ma J, Zhang L, Niu F, Feng T, Li C (2016) Auricular vagus nerve stimulation promotes functional recovery and enhances the post-ischemic angiogenic response in an ischemia/reperfusion rat model. Neurochem Int. doi:10.1016/j.neuint.2016.02.009
Jones BE (1993) The organization of central cholinergic systems and their functional importance in sleep-waking states. Prog Brain Res 98:61–71
Jones BE (2004) Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog Brain Res 145:157–169
Jones BE, Cuello AC (1989) Afferents to the basal forebrain cholinergic cell area from pontomesencephalic–catecholamine, serotonin, and acetylcholine–neurons. Neuroscience 31:37–61
Jones DT, Knopman DS, Gunter JL, Graff-Radford J, Vemuri P, Boeve BF, Petersen RC, Weiner MW, Jack CR Jr (2016) Cascading network failure across the Alzheimer’s disease spectrum. Brain 139:547–562
Julin P, Wahlund LO, Basun H, Persson A, Måre K, Rudberg U (1995) Clinical diagnosis of frontal lobe dementia and Alzheimer’s disease: relation to cerebral perfusion, brain atrophy and electroencephalography. Dementia 6:142–147
Juric DM, Loncar D, Carman-Krzan M (2008) Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors. Neurochem Int 52:297–306
Kadir A, Almkvist O, Wall A, Langstrom B, Nordberg A (2006) PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer’s disease. Psychopharmacology (Berlin) 188:509–520
Kalinin S, Gavrilyuk V, Polak PE, Vasser R, Zhao J, Heneka MT, Feinstein DL (2007) Noradrenaline deficiency in brain increases beta-amyloid plaque burden in an animal model of Alzheimer’s disease. Neurobiol Aging 28:1206–1214
Kang JI, Huppé-Gourgues F, Vaucher E (2014) Boosting visual cortex function and plasticity with acetylcholine to enhance visual perception. Front Syst Neurosci 8:172
Kassab A, Schaub F, Vent J, Hüttenbrink KB, Damm M (2009) Effects of short inter-stimulus intervals on olfactory and trigeminal event-related potentials. Acta Otolaryngol 129:1250–1256
Kastrup A, Baudewig J, Schnaudigel S, Huonker R, Becker L, Sohns JM, Dechent P, Klingner C, Witte OW (2008) Behavioral correlates of negative BOLD signal changes in the primary somatosensory cortex. Neuroimage 41:1364–1371
Kawai H, Lazar R, Metherate R (2007) Nicotinic control of axon excitability regulates thalamocortical transmission. Nat Neurosci 10:1168–1175
Kawamata J, Shimohama S (2011) Stimulating nicotinic receptors trigger multiple pathways attenuating cytotoxicity in models of Alzheimer’s and Parkinson’s diseases. J Alzheimers Dis 24:95–109
Kennedy AM, Frackowiak RS, Newman SK, Bloomfield PM, Seaward J, Roques P, Lewington G, Cunningham VJ, Rossor MN (1995) Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer’s disease. Neurosci Lett 186:17–20
Kerbler GM, Hamlin AS, Pannek K, Kurniawan ND, Keller MD, Rose SE, Coulson EJ (2013) Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66:133–141
Kerbler GM, Fripp J, Rowe CC, Villemagne VL, Salvado O, Rose S, Coulson EJ (2014) Basal forebrain atrophy correlates with amyloid β burden in Alzheimer’s disease. Neuroimage Clin 7:105–113
Kerbler GM, Nedelska Z, Fripp J, Laczó J, Vyhnalek M, Lisý J, Hamlin AS, Rose S, Hort J, Coulson EJ (2015) Basal forebrain atrophy contributes to allocentric navigation impairment in Alzheimer’s disease patients. Front Aging Neurosci 7:185
Kermen F, Sultan S, Sacquet J, Mandairon N, Didier A (2010) Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory. PLoS One 5:e12118
Kern RC, Conley DB, Haines GK 3rd, Robinson AM (2004) Treatment of olfactory dysfunction. II: Studies with minocycline. Laryngoscope 114:2200–2204
Khalil Z, Ralevic V, Bassirat M, Dusting GJ, Helme RD (1994) Effects of ageing on sensory nerve function in rat skin. Brain Res 641:265–272
Kihara T, Shimohama S, Sawada H, Kimura J, Kume T, Kochiyama H, Maeda T, Akaike A (1997) Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol 42:159–163
Kimoff RJ, Sforza E, Champagne V, Ofiara L, Gendron D (2001) Upper airway sensation in snoring and obstructive sleep apnea. Am J Respir Crit Care Med 164:250–255
Kitayama IT, Otani M, Murase S (2008) Degeneration of the locus ceruleus noradrenergic neurons in the stress-induced depression of rats. Ann N Y Acad Sci 1148:95–98
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 25:8843–8853
Kitazawa M, Cheng D, Tsukamoto MR, Koike MA, Wes PD, Vasilevko V, Cribbs DH, LaFerla FM (2011) Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal β-catenin pathway function in an Alzheimer’s disease model. J Immunol 187:6539–6549
Knafo S, Ariav G, Barkai E, Libersat F (2004) Olfactory learning-induced increase in spine density along the apical dendrites of CA1 hippocampal neurons. Hippocampus 14:819–825
Ko S, Simonsick E, Deshpande N (2015) Luigi Ferrucci L (2015) Sex-specific age associations of ankle proprioception test performance in older adults: results from the Baltimore Longitudinal Study of Aging. Age Ageing 44:485–490
Kobayashi Y, Amaral DG (2003) Macaque monkey retrosplenial cortex: II. Cortical afferents. J Comp Neurol 466:48–79
Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 32:160–169
Kogure D, Matsuda H, Ohnishi T, Asada T, Uno M, Kunihiro T, Nakano S, Takasaki M (2000) Longitudinal evaluation of early Alzheimer’s disease using brain perfusion SPECT. J Nucl Med 41:1155–1162
Konstantinidis I, Tsakiropoulou E, Bekiaridou P, Kazantzidou C, Constantinidis J (2013) Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope 123:E85–E90
Krupa DJ, Wiest MC, Shuler MG, Laubach M, Nicolelis MAL (2004) Layer-specific somatosensory cortical activation during active tactile discrimination. Science 304:1989–1992
Kubota S, Hirano M, Morishita T, Uehara K, Funase K (2015) Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons. NeuroReport 26:249–253
Kumaran D, Maguire EA (2006) An unexpected sequence of events: mismatch detection in the human hippocampus. PLoS Biol 4:e424
Kuo MC, Rasmusson DD, Dringenberg HC (2009) Input-selective potentiation and rebalancing of primary sensory cortex afferents by endogenous acetylcholine. Neuroscience 163:430–441
Kurosawa M, Sato A, Sato Y (1992) Cutaneous mechanical sensory stimulation increases extracellular acetylcholine release in cerebral cortex in anesthetized rats. Neurochem Int 21:423–427
Kuznetsova E, Schliebs R (2013) β-Amyloid, cholinergic transmission, and cerebrovascular system—a developmental study in a mouse model of Alzheimer’s disease. Curr Pharm Des 19:6749–6765
Lai YY, Kodama T, Siegel JM (2001) Changes in monoamine release in the ventral horn and hypoglossal nucleus linked to pontine inhibition of muscle tone: an in vivo microdialysis study. J Neurosci 21:7384–7391
Larsson M, Hedner M, Papenberg G, Seubert J, Bäckman L, Laukka EJ (2016) Olfactory memory in the old and very old: relations to episodic and semantic memory and APOE genotype. Neurobiol Aging 38:118–126
Lashgari R, Khakpour-Taleghani B, Motamedi F, Shahidi S (2008) Effects of reversible inactivation of locus coeruleus on long-term potentiation in perforant path-DG synapses in rats. Neurobiol Learn Mem 90:309–316
Laursen B, Mørk A, Plath N, Kristiansen U, Bastlund JF (2014) Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. Brain Res 1543:253–262
Lavzin M, Rapoport S, Polsky A, Garion L, Schiller J (2012) Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo. Nature 490:397–401
Leanza G, Nikkhah G, Nilsson OG, Wiley RG, Björklund A (1996) Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions. J Comp Neurol 373:355–357
Lee SC, Collins M, Vanguri P, Shin ML (1992) Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J Immunol 148:3391–3397
Lee I, Yoganarasimha D, Rao G, Knierim JJ (2004) Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3. Nature 430:456–459
Lee YS, Bailey CH, Kandel ER, Kaang BK (2008) Transcriptional regulation of long-term memory in the marine snail Aplysia. Mol Brain 1:3
Lee AC, Tian H, Grosmaitre X, Ma M (2009) Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. Chem Senses 34:695–703
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 7:56
Lee CW, Shih YH, Wu SY, Yang T, Lin C, Kuo YM (2013) Hypoglycemia induces tau hyperphosphorylation. Curr Alzheimer Res 10:298–308
Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S et al (1990) Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain 113:27–47
Lenk S, Bluschke A, Beste C (2014) Olfactory short-term memory encoding and maintenance—an event-related potential study. Neuroimage 98:475–486
Lennertz RC, Medler KA, Bain JL, Wright DE, Stucky CL (2011) Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy. J Neurophysiol 106:905–914
Lepousez G, Nissant A, Bryant AK, Gheusi G, Greer CA, Lledo PM (2014) Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons. Proc Natl Acad Sci USA 111:13984–13989
Levin BE, Dunn-Meynell A (1991) Adult rat barrel cortex plasticity occurs at 1 week but not at 1 day after vibrissectomy as demonstrated by the 2-deoxyglucose method. Exp Neurol 113:237–248
Levine ES, Litto WJ, Jacobs BL (1990) Activity of cat locus coeruleus noradrenergic neurons during the defense reaction. Brain Res 531:189–195
Levy LM, Henkin RI, Lin CS, Hutter A, Sclesinger D (1998) Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI. J Comput Assist Tomogr 22:760–770
Li KZ, Lindenberger U (2002) Relations between aging sensory/sensorimotor and cognitive functions. Neurosci Biobehav Rev 26:777–783
Li A, Nattie E (2006) Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability. J Physiol 570:385–396
Li YQ, Takada M, Mizuno M (1993) premotor neurons projecting simultaneously to two orofacial motor nuclei by sending their branched axons. A study with a fluorescent retrograde double-labelling technique in the rat. Neurosci Lett 152:29–32
Li A, Emond L, Nattie E (2008) Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function. Adv Exp Med Biol 605:371–376
Lim HK, Nebes R, Snitz B, Cohen A, Mathis C, Price J, Weissfeld L, Klunk W (2014) Aizenstein HJ (2014) Regional amyloid burden and intrinsic connectivity networks in cognitively normal elderly subjects. Brain 137:3327–3338
Lin FR (2011) Hearing loss and cognition among older adults in the United States. J Gerontol A Biol Sci Med Sci 66:1131–1136
Lin FR, Yaffe K, Xia J, Xue QL, Harris TB, Purchase-Helzner E, Satterfield S, Ayonayon HN, Ferrucci L, Simonsick EM (2013) Hearing loss and cognitive decline in older adults. JAMA Intern Med 173:293–299
Linster C, Nai Q, Ennis M (2011) Nonlinear effects of noradrenergic modulation of olfactory bulb function in adult rodents. J Neurophysiol 105:1432–1443
Lisman JE (1999) Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. Neuron 22:233–242
Liu X, Basavaraj S, Krishnan R, Yan J (2011) Contributions of the thalamocortical system towards sound-specific auditory plasticity. Neurosci Biobehav Rev 35:2155–2161
Liu X, Ye K, Weinshenker D (2015) Norepinephrine Protects against Amyloid-β Toxicity via TrkB. J Alzheimers Dis 44:251–260
Lockrow J, Boger H, Bimonte-Nelson H, Granholm AC (2011a) Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. Behav Brain Res 221:610–622
Lockrow J, Boger H, Gerhardt G, Aston-Jones G, Bachman D, Granholm AC (2011b) A noradrenergic lesion exacerbates neurodegeneration in a Down syndrome mouse model. J Alzheimers Dis 23:471–489
Logroscino G, Panza F (2016) The role of hearing impairment in cognitive decline: need for the special sense assessment in evaluating cognition in older age. Neuroepidemiology 46:290–291
Loughlin AJ, Woodroofe MN, Cuzner ML (1993) Modulation of interferon-gamma-induced major histocompatibility complex class II and Fc receptor expression on isolated microglia by transforming growth factor-beta 1, interleukin-4, noradrenaline and glucocorticoids. Immunology 79:125–130
Lu SM, Yeh HH (1999) Ethanol modulates AMPA-induced current responses of primary somatosensory cortical neurons. Neurochem Int 35:175–183
Lukiw WJ (2004) Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling. Neurochem Res 29:1287–1297
Luo Y, Zhou J, Li MX, Wu PF, Hu ZL, Ni L, Jin Y, Chen JG, Wang F (2015) Reversal of aging-related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors. Aging Cell 14:170–179
Machado JC, Genaro G (2014) Influence of olfactory enrichment on the exploratory behaviour of captive-housed domestic cats. Aust Vet J 92:492–498
Madrigal JL, Kalinin S, Richardson JC, Feinstein DL (2007) Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta. J Neurochem 103:2092–2101
Madrigal JL, Leza JC, Polak P, Kalinin S, Feinstein DL (2009) Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. J Neurosci 29:263–267
Maisonobe Th, Tankere F, Lamas G, Soundant J, Bouche P, Willer JC, Fournier E (1998) Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects. Brain Res 810:220–228
Maiya RP, Messing RO (2014) Peripheral systems: neuropathy. Handb Clin Neurol 125:513–525
Manaye KF, Mouton PR, Xu G, Drew A, Lei DL, Sharma Y, Rebeck GW, Turner S (2013) Age-related loss of noradrenergic neurons in the brains of triple transgenic mice. Age (Dordr) 35:139–147
Mann DM (1983) The locus coeruleus and its possible role in ageing and degenerative disease of the human central nervous system. Mech Ageing Dev 23:73–94
Mann DM, Lincoln J, Yates PO, Stamp JE, Toper S (1980) Changes in the monoamine containing neurones of the human CNS in senile dementia. Br J Psychiat 136:533–541
Mann DM, Yates PO, Hawkes J (1982) The noradrenergic system in Alzheimer and multi-farct dementias. J Neurosurgic Psychiatry 45:113–119
Mann DM, Yates PO, Hawkes J (1983) The pathology of the human locus ceruleus. Clin Neuropathol 2:1–7
Mann DM, Yates PO, Marcyniuk B (1984a) A comparison of changes in the nucleus basalis and locus caeruleus in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 47:201–203
Mann DM, Yates PO, Marcyniuk B (1984b) Monoaminergic neurotransmitter systems in presenile Alzheimer’s disease and in senile dementia of the Alzheimer type. Clin Neuropathol 3:199–205
Manning H, Tremblay F (2006) Age differences in tactile pattern recognition at the fingertip. Somatosens Mot Res 23:147–155
Maphis N, Xu G, Kokiko-Cochran ON, Jiang S, Cardona A, Ransohoff RM, Lamb BT, Bhaskar K (2015a) Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain 138:1738–1755
Maphis N, Xu G, Kokiko-Cochran ON, Cardona AE, Ransohoff RM, Lamb BT, Bhaskar K (2015b) Loss of tau rescues inflammation-mediated neurodegeneration. Front Neurosci 9:196
Marcantoni A, Raymond EF, Carbone E, Marie H (2014) Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer’s disease transgenic model. Pflugers Arch 466:1437–1450
Marcyniuk B, Mann DM, Yates PO (1986a) Loss of nerve cells from locus coeruleus in Alzheimer’s disease is topographically arranged. Neurosci Lett 64:247–252
Marcyniuk B, Mann DM, Yates PO (1986b) The topography of cell loss from locus caeruleus in Alzheimer’s disease. J Neurol Sci 76:335–345
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63:38–46
Marrero MB, Bencherif M (2009) Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: central role for JAK2 activation of STAT3 and NF-kappaB. Brain Res 1256:1–7
Marsh L, Biglan K, Gerstenhaber M, Williams JR (2009) Atomoxetine for the treatment of executive dysfunction in Parkinson’s disease: a pilot open-label study. Mov Disord 24:277–282
Marshall L, Born J (2007) The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 11:442–450
Martins AR, Froemke RC (2015) Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex. Nat Neurosci 18:1483–1492
Masdeu JC, Zubieta JL, Arbizu J (2005) Neuroimaging as a marker of the onset and progression of Alzheimer’s disease. J Neurol Sci 236:55–64
Master S, Larue M, Tremblay F (2010) Characterization of human tactile pattern recognition performance at different ages. Somatosens Mot Res 27:60–67
Matsumoto H, Kashiwadani H, Nagao H, Aiba A, Mori K (2009) Odor-induced persistent discharge of mitral cells in the mouse olfactory bulb. J Neurophysiol 101:1890–1900
Matsunaga W, Shirokawa T, Isobe K (2004) BDNF is necessary for maintenance of noradrenergic innervations in the aged rat brain. Neurobiol Aging 25:341–348
Matthews KL, Chen CP, Esiri MM (2002) Noradreneric changes, aggressive behavior, and cognition in patients with dementia. Biol Psychiatry 51:407–416
Mattson MP (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77:1081–1132
McCormick DA, Pape HC, Williamson A (1991) Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system. Prog Brain Res 88:293–305
McGinty D, Szymusiak R (1988) Neuronal unit activity patterns in behaving animals: brainstem and limbic system. Annu Rev Psychol 39:135–168
McIntosh AR (1999) Mapping cognition to the brain through neural interactions. Memory 7:523–548
McKinney M, Jacksonville MC (2005) Brain cholinergic vulnerability: relevance to behavior and disease. Biochem Pharmacol 70:1115–1124
McNamee EN, Ryan KM, Griffin EW, González-Reyes RE, Ryan KJ, Harkin A, Connor TJ (2010) Noradrenaline acting at central beta-adrenoceptors induces interleukin-10 and suppressor of cytokine signaling-3 expression in rat brain: implications for neurodegeneration. Brain Behav Immun 24:660–671
McQuail JA, Riddle DR, Nicolle MM (2010) Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain. Neurobiol Aging 32:2322.e1–2322.e4
Mello-Carpes PB, Izquierdo I (2013) the nucleus of the solitary tract → nucleus paragigantocellularis → locus coeruleus → CA1 region of dorsal hippocampus pathway is important for consolidation of object recognition memory. Neurobiol Learn Mem 100:56–63
Mentis MJ, Horwitz B, Grady CL, Alexander GE, VanMeter JW, Maisog JM, Pietrini P, Schapiro MB, Rapoport SI (1996) Visual cortical dysfunction in Alzheimer’s disease evaluated with a temporally graded “stress test” during PET. Am J Psychiatry 153:32–40
Merhi M, Helme RD, Khalil Z (1998) Age-related changes in sympathetic modulation of sensory nerve activity in rat skin. Inflamm Res 47:239–244
Mesulam MM (1998) From sensation to cognition. Brain 121:1013–1052
Mesulam M (2004) The cholinergic lesion of Alzheimer’s disease: pivotal factor or side show? Learning and Memory 11:43–49
Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214:170–197
Metherate R (2004) Nicotinic acetylcholine receptors in sensory cortex. Learn Mem 11:50–59
Metherate R (2011) Functional connectivity and cholinergic modulation in auditory cortex. Neurosci Biobehav Rev 35:2058–2063
Metherate R, Intskirveli I, Kawai HD (2012) Nicotinic filtering of sensory processing in auditory cortex. Front Behav Neurosci 6:44
Meyer JS, Rauch GM, Crawford K, Rauch RA, Konno S, Akiyama H, Terayama Y, Haque A (1999) Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia. Int J Geriatr Psychiatry 14:1050–1061
Meyer SR, Spaan PE, Boelaarts L, Ponds RW, Schmand B, de Jonghe JF (2016) Visual associations cued recall a paradigm for measuring episodic memory decline in Alzheimer’s disease. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 23:566–577
Miklic S, Juric DM, Carman-Krzan M (2004) Differences in the regulation of BDNF and NGF synthesis in cultured neonatal rat astrocytes. Int J Dev Neurosci 22:119–130
Minger SL, Esiri MM, McDonald B, Keene J, Carter J, Hope T, Francis PT (2000) Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology 55:1460–1467
Mintun MA, Lundstrom BN, Snyder AZ, Vlassenko AG, Shulman GL, Raichle ME (2001) Blood flow and oxygen delivery to human brain during functional activity: theoretical modeling and experimental data. Proc Natl Acad Sci USA 98:6859–6864
Misiak B, Leszek J, Kiejna A (2012) Metabolic syndrome, mild cognitive impairment and Alzheimer’s disease–the emerging role of systemic low-grade inflammation and adiposity. Brain Res Bull 89:144–149
Missonnier P, Ragot R, Derouesné C, Guez D, Renault B (1999) Automatic attentional shifts induced by a noradrenergic drug in Alzheimer’s disease: evidence from evoked potentials. Int J Psychophysiol 33:243–251
Mitolo M, Gardini S, Fasano F, Crisi G, Pelosi A, Pazzaglia F, Caffarra P (2013) Visuospatial memory and neuroimaging correlates in mild cognitive impairment. J Alzheimers Dis 35:75–90
Mitsis EM, Cosgrove KP, Staley JK, Frohlich EB, Bois F, Tamagnan GD, Estok KM, Seibyl JP, Van Dyck CH (2007) [123I]5-IA-85380 SPECT imaging of beta2-nicotinic acetylcholine receptor availability in the aging human brain. Ann N Y Acad Sci 1097:168–170
Mold JW, Vesely SK, Keyl BA, Schenk JB, Roberts M (2004) The prevalence, predictors, and consequences of peripheral sensory neuropathy in older patients. J Am Board Fam Pract 17:309–318
Mold JW, Lawler F, Roberts M (2008) The health consequences of peripheral neurological deficits in an elderly cohort: an Oklahoma Physicians Resource/Research Network Study. J Am Geriatr Soc 56:1259–1264
Morse JK, Wiegand SJ, Anderson K, You Y, Cai N, Carnahan J, Miller J, DiStefano PS, Altar CA, Lindsay RM et al (1993) Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci 13:4146–4156
Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, Holthoff V, Salmon E, Baron JC, De Cristofaro MT, Padovani A, Borroni B, Franceschi M, Bracco L, Pupi A (2004) MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 63:2332–2340
Mouton PR, Kelley-Bell B, Tweedie D, Spangler EL, Perez E, Carlson OD, Short RG, Decabo R, Chang J, Ingram DK, Li Y, Greig NH (2012) The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons. Neurobiol Aging 33:423.e27–423.e36
Mrak RE, Sheng JG, Griffin WS (1995) Glial cytokines in Alzheimer’s disease: review and pathogenic implications. Hum Pathol 26:816–823
Mueggler T, Sturchler-Pierrat C, Baumann D, Rausch M, Staufenbiel M, Rudin M (2002) Compromised hemodynamic response in amyloid precursor protein transgenic mice. J Neurosci 22:7218–7224
Mullin WJ, Phillis JW (1975) The effects of graded forelimb afferent volleys on acetylcholine release from cat sensorimotor cortex. J Physiol 244:741–756
Nagahara AH, Bernot T, Moseanko R, Brignolo L, Blesch A, Conner JM, Ramirez A, Gasmi M, Tuszynski MH (2009) Long-term reversal of cholinergic neuronal decline in aged non-human primates by lentiviral NGF gene delivery. Exp Neurol 215:153–159
Nakanishi H (2003) Microglial functions and proteases. Mol Neurobiol 27:163–176
Naveh-Benjamin M, Kilb A (2014) Age-related differences in associative memory: the role of sensory decline. Psychol Aging 29:672–683
Neal MJ, Hemsworth BA, Mitchell JF (1968) The excitation of central cholinergic mechanisms by stimulation of the auditory pathway. Life Sci 7:757–763
Nelson CL, Sarter M, Bruno JP (2005) Prefrontal cortical modulation of acetylcholine release in posterior parietal cortex. Neuroscience 132:347–359
Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV (2015) Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Biochim Biophys Acta. doi:10.1016/j.bbadis.2015.12.016
Newman LA, Darling J, McGaughy J (2008) Atomoxetine reverses attentional deficits produced by noradrenergic deafferentation of medial prefrontal cortex. Psychopharmacology 200:39–50
Niehaus L, Lehmann R, Röricht S, Meyer BU (2001) Age-related reduction in visually evoked cerebral blood flow responses. Neurobiol Aging 22:35–38
Niewiadomska G, Wyrzykowska J, Chechłacz M (2000) Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies? Acta Biochim Pol 47:313–330
Niwa K, Younkin L, Ebeling C, Turner SK, Westaway D, Younkin S, Ashe KH, Carlson GA, Iadecola C (2000) Abeta 1–40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci USA 97:9735–9740
Nobili F, Koulibaly M, Vitali P, Migneco O, Mariani G, Ebmeier K, Pupi A, Robert PH, Rodriguez G, Darcourt J (2002) Brain perfusion follow-up in Alzheimer’s patients during treatment with acetylcholinesterase inhibitors. J Nucl Med 43:983–990
Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B (1995) Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains—in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9:21–27
Nuñez A, Domínguez S, Buño W, Fernández de Sevilla D (2012) Cholinergic-mediated response enhancement in barrel cortex layer V pyramidal neurons. J Neurophysiol 108:1656–1668
Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG (2011) The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine. Behav Brain Res 221:594–603
O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SCR, Markus HS (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57:632–638
O’Brien JT, Eagger S, Syed GM, Sahakian BJ, Levy R (1992) A study of regional cerebral blood flow and cognitive performance in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 55:1182–1187
Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39:409–421
Ogawa T, Takezawa K, Shimizu S, Shimizu T (2014) Valproic acid promotes neural regeneration of olfactory epithelium in adult mice after methimazole-induced damage. Am J Rhinol Allergy 28:e95–e99
O’Neil JN, Mouton PR, Tizabi Y, Ottinger MA, Lei DL, Ingram DK, Manaye KF (2007) Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice. J Chem Neuroanat 34:102–107
O’Neill MJ, Murray TK, Lakics V, Visanji NP, Duty S (2002) The role of neuronal nicotinic acetylcholine receptors in acute and chronic neurodegeneration. Curr Drug Targets CNS Neurol Disord 1:399–411
Ontiveros-Torres MÁ, Labra-Barrios ML, Díaz-Cintra S, Aguilar-Vázquez AR, Moreno-Campuzano S, Flores-Rodríguez P, Luna-Herrera C, Mena R, Perry G, Florán-Garduño B, Luna-Muñoz J, Luna-Arias JP (2016) Fibrillar Amyloid-β Accumulation Triggers an Inflammatory Mechanism Leading to Hyperphosphorylation of the Carboxyl-Terminal End of Tau Polypeptide in the Hippocampal Formation of the 3xTg-AD Transgenic Mouse. J Alzheimers Dis 52:243–269
Ori C, Freo U, Pizzolato G, Dam M (2002) Effects of acetyl-l-carnitine on regional cerebral glucose metabolism in awake rats. Brain Res 951:330–335
Oshima E, Terada S, Sato S, Ikeda C, Oda K, Inoue S, Kawada K, Yokota O, Uchitomi Y (2014) Left frontal lobe hypoperfusion and depressive symptoms in Alzheimer’s disease patients taking cholinesterase inhibitors. Psychiatry Res 224:319–323
Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, O’Neil JP, Janabi M, Lazaris A, Cantwell A, Vogel J, Santos M, Miller ZA, Bettcher BM, Vossel KA, Kramer JH, Gorno-Tempini ML, Miller BL, Jagust WJ, Rabinovici GD (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain 139:1551–1567
Paban V, Jaffard M, Chambon C, Malafosse M, Alescio-Lautier B (2005) Time course of behavioral changes following basal forebrain cholinergic damage in rats: environmental enrichment as a therapeutic intervention. Neuroscience 132:13–32
Palmer AM, Wilcock GK, Esiri MM, Francis PT, Bowen DM (1987a) Monoaminergic innervation of the frontal and temporal lobes in Alzheimer’s disease. Brain Res 401:231–238
Palmer AM, Francis PT, Bowen DM, Benton JS, Neary D, Mann DM, Snowden JS (1987b) Catecholaminergic neurons assessed ante-mortem in Alzheimer’s disease. Brain Res 414:365–375
Panneton WM (1991) Primary afferent projections from the upper respiratory tract in the muskrat. J Comp Neurol 308:51–65
Pantano P, Baron JC, Lebrun-Grandie P, Duquesnoy N, Bousser MG, Comar D (1984) Regional cerebral blood flow and oxygen consumption in human aging. Stroke 15:635–641
Panza F, Frisardi V, Capurso C, Imbimbo BP, Vendemiale G, Santamato A, D’Onofrio G, Seripa D, Sancarlo D, Pilotto A, Solfrizzi V (2007) Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms. J Alzheimers Dis 21:691–724
Panza F, Solfrizzi V, Frisardi V, Maggi S, Sancarlo D, Adante F, D’Onofrio G, Seripa D, Pilotto A (2011) Different models of frailty in predementia and dementia syndromes. J Nutr Health Aging 15:711–719
Panza F, Solfrizzi V, Logroscino G (2015a) Age-related hearing impairment-a risk factor and frailty marker for dementia and AD. Nat Rev Neurol 11:166–175
Panza F, Solfrizzi V, Seripa D, Imbimbo BP, Capozzo R, Quaranta N, Pilotto A, Logroscino G (2015b) Age-related hearing impairment and frailty in Alzheimer’s disease: interconnected associations and mechanisms. Front Aging Neurosci 7:113
Papadopoulos GC, Parnavelas JG, Buijs RM (1989) Light and electron microscopic immunocytochemical analysis of the noradrenaline innervation of the rat visual cortex. J Neurocytol 18:1–10
Paquet C, Boissonnot M, Roger F, Dighiero P, Gil R, Hugon J (2007) Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett 420:97–99
Parianen Lesemann FH, Reuter EM, Godde B (2015) Tactile stimulation interventions: influence of stimulation parameters on sensorimotor behavior and neurophysiological correlates in healthy and clinical samples. Neurosci Biobehav Rev 51:126–137
Park L, Anrather J, Forster C, Kazama K, Carlson GA, Iadecola C (2004) Abeta-induced vascular oxidative stress and attenuation of functional hyperemia in mouse somatosensory cortex. J Cereb Blood Flow Metab 24:334–342
Park L, Anrather J, Zhou P, Frys K, Pitstick R, Younkin S, Carlson GA, Iadecola C (2005) NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci 25:1769–1777
Pennanen C, Kivipelto M, Tuomainen S, Hartikainen P, Hanninen T, Laakso MP, Hallikainen M, Vanhanen M, Nissinen A, Helkala EL, Vainio P, Vanninen R, Partanen K, Soininen H (2004) Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging 25:303–310
Peracino A (2014) Hearing loss and dementia in the aging population. Audiol Neurootol 19:6–9
Pereira A, Ribeiro S, Wiest M, Moore L, Pantoja J, Shih-Chieh Lin S, Miguel AL, Nicolelis MAL (2007) Processing of tactile information by the hippocampus. Proc Nat Acad Sci. USA 104:18286–18291
Peternel A, Hughey D, Wenk G, Olton D (1988) Basal forebrain and memory: neurotoxic lesions impair serial reversals of a spatial discrimination. Psychobiology 16:54–58
Petrella JR, Coleman RE, Doraiswamy PM (2003) Neuroimaging and early diagnosis of Alzheimer disease: a look to the future. Radiology 226:315–336
Petzold GC, Murthy VN (2011) Role of astrocytes in neurovascular coupling. Neuron 71:782–797
Pluta R, Jabłoński M, Ułamek-Kozioł M, Kocki J, Brzozowska J, Januszewski S, Furmaga-Jabłońska W, Bogucka-Kocka A, Maciejewski R, Czuczwar SJ (2013) Sporadic Alzheimer’s disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer’s disease genes. Mol Neurobiol 48:500–515
Poorthuis RB, Goriounova NA, Couey JJ (2009) Mansvelder HD (2009) Nicotinic actions on neuronal networks for cognition: general principles and long-term consequences. Biochem Pharmacol 78:668–676
Popratiloff AS, Streppel M, Guart A, Guntinas-Lichius O, Angelov DN, Stennert E, Delgardo-Garcia JM, Neis WF (2001) Hypoglossal and reticular interneurons involved in orofacial coordination in the rat. J Comp Neurol 433:364–379
Prediger RD, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats. Involvement of adenosine A1 and A2A receptors. Neurobiol Aging 26:957–964
Prediger RD, De-Mello N, Takahashi RN (2006) Pilocarpine improves olfactory discrimination and social recognition memory deficits in 24 month-old rats. Eur J Pharmacol 531:176–182
Quaranta N, Coppola F, Casulli M, Barulli MR, Panza F, Tortelli R, Capozzo R, Leo A, Tursi M, Grasso A, Solfrizzi V, Sobbà C, Logroscino G (2014) The prevalence of peripheral and central hearing impairment and its relation to cognition in older adults. Audiol Neurootol 19:10–14
Quiroga RQ, Reddy L, Kreiman G, Koch C, Fried I (2005) Invariant visual representation by single neurons in the human brain. Nature 435:1102–1107
Rácz E, Bácskai T, Szabo G, Székely G, Matesz C (2008) Organization of last-order premotor interneurons related to the protraction of tongue in the frog, Rana esculenta. Brain Res 1187:111–115
Rajkowski J, Kubiak P, Aston-Jones G (1994) Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance. Brain Res Bull 35:607–616
Rajkowski J, Majczynski H, Clayton E, Aston-Jones G (2004) Activation of monkey locus coeruleus neurons varies with difficulty and performance in a target detection task. J Neurophysiol 92:361–371
Ramos BP, Arnsten AF (2007) Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 113:523–536
Rapoport SI, Grady CL (1993) Parametric in vivo brain imaging during activation to examine pathological mechanisms of functional failure in Alzheimer disease. Int J Neurosci 70:39–56
Rasch B, Büchel C, Gais S, Born J (2007) Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 315:1426–1429
Rasmusson DD, Clow K, Szerb JC (1994) Modification of neocortical acetylcholine release and electroencephalogram desynchronization due to brainstem stimulation by drugs applied to the basal forebrain. Neuroscience 60:665–677
Rasmusson DD, Smith SA, Semba K (2007) Inactivation of prefrontal cortex abolishes cortical acetylcholine release evoked by sensory or sensory pathway stimulation in the rat. Neuroscience 149:232–241
Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15:1676–1689
Redmond CL, Bain GI, Laslett LL, McNeil JD (2012) Deteriorating tactile sensation in patients with hand syndromes associated with diabetes: a two-year observational study. J Diabetes Complications 26:313–318
Reid AT, Harley CW (2010) An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat. Exp Brain Res 200:151–159
Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 334:752–758
Reinikainen KJ, Soininen H, Riekkinen PJ (1990) Neurotransmitter changes in Alzheimer’s disease: implications to diagnostics and therapy. J Neurosci Res 27:576–586
Ressler KJ, Nemeroff CB (1999) Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry 46:1219–1233
Restivo L, Roman FS, Ammassari-Teule M, Marchetti E (2006) Simultaneous olfactory discrimination elicits a strain-specific increase in dendritic spines in the hippocampus of inbred mice. Hippocampus 16:472–479
Rey NL, Jardanhazi-Kurutz D, Terwel D, Kummer MP, Jourdan F, Didier A, Heneka MT (2012) Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice. Neurobiol Aging 33:426.e1–426.e11
Riley CP, Cope TC, Buck CR (2004) CNS neurotrophins are biologically active and expressed by multiple cell types. J Mol Histol 35:771–783
Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM (2005) Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimers Dis 8:247–268
Robbins TW, Arnsten AF (2009) The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 32:267–287
Rokem A (2013) Silver MA (2013) The benefits of cholinergic enhancement during perceptual learning are long-lasting. Front Comput Neurosci. 7:66
Roland PE, Seitz RJ (1991) Positron emission tomography studies of the somatosensory system in man. Ciba Found Symp 163:113–120
Rolls ET (2004) The functions of the orbitofrontal cortex. Brain Cogn 55:11–29
Rommelfanger KS, Weinshenker D (2007) Norepinephrine: the redheaded stepchild of Parkinson’s disease. Biochem Pharmacol 74:177–190
Room P, Groenewegen HJ (1986) Connections of the parahippocampal cortex. I. Cortical afferents. J Comp Neurol 251:415–450
Ross MH, Yurgelun-Todd DA, Renshaw PF, Maas LC, Mendelson JH, Mello NK, Cohen BM, Levin JM (1997) Age-related reduction in functional MRI response to photic stimulation. Neurology 48:173–176
Rukhadze I, Kubin L (2007) Differential pontomedullary catecholaminergic projections to hypoglossal motor nucleus and viscerosensory nucleus of the solitary tract. J Chem Neuroanat 33:23–33
Runfeldt MJ, Sadovsky AJ, MacLean JN (2014) Acetylcholine functionally reorganizes neocortical microcircuits. J Neurophysiol 112:1205–1216
Safaai H, Neves R, Eschenko O, Logothetis NK, Panzeri S (2015) Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing. Proc Natl Acad Sci USA 112:12834–12839
Salminen A, Kauppinen A, Suuronen T, Kaarniranta K, Ojala J (2009) ER stress in Alzheimer’s disease: a novel neuronal trigger for inflammation and Alzheimer’s pathology. J Neuroinflammation 6:41
Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211–223
Sarter M, Bruno JP (2000) Cortical cholinergic inputs mediating arousal, attentional processing and dreaming: differential afferent regulation of the basal forebrain by telencephalic and brainstem afferents. Neuroscience 95:933–952
Sarter M, Hasselmo ME, Bruno JP, Givens B (2005) Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res Brain Res Rev 48:98–111
Sasaki A, Kawarabayashi T, Murakami T, Matsubara E, Ikeda M, Hagiwara H, Westaway D, George-Hyslop PS, Shoji M, Nakazato Y (2008) Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice TgTauP301L. Brain Res 1214:159–168
Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 275:321–328
Scheibel AB, Duong TH, Tomiyasu U (1987) Denervation microangiopathy in senile dementia, Alzheimer type. Alzheimer Dis Assoc Disord 1:19–37
Schild L, Reiser G (2005) Oxidative stress is involved in the permeabilization of the inner membrane of brain mitochondria exposed to hypoxia/reoxygenation and low micromolar Ca2+. FEBS J 272:3593–3601
Schillaci G, Battista F, Fiorenzano G, Basili MC, Crapa M, Alrashdi Y, Pucci G (2015) Obstructive sleep apnea and cardiovascular disease—a new target for treatment. Curr Pharm Des 21:3496–3504
Schliebs R, Arendt T (2011) The cholinergic system in aging and neuronal degeneration. Behav Brain Res 221:555–563
Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA (2009) The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66:200–208
Schriever VA, Lehmann S, Prange J, Hummel T (2014) Preventing olfactory deterioration: olfactory training may be of help in older people. J Am Geriatr Soc 62:384–386
Schwaber JS, Kapp BS, Higgins GA, Rapp PR (1982) Amygdaloid and basal forebrain direct connections with the nucleus of the solitary tract and the dorsal motor nucleus. J Neurosci 2:1424–1438
Scott JA, Braskie MN, Tosun D, Thompson PM, Weiner M, DeCarli C, Carmichael OT (2015) Cerebral amyloid and hypertension are independently associated with white matter lesions in elderly. Front Aging Neurosci 7:221
Séguéla P, Watkins KC, Geffard M, Descarries L (1990) Noradrenaline axon terminals in adult rat neocortex: an immunocytochemical analysis in serial thin sections. Neuroscience 35:249–264
Selkoe DJ (1999) Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature (London) 399:A23–A31
Semba K (2000) Multiple output pathways of the basal forebrain: organization, chemical heterogeneity, and roles in vigilance. Behav Brain Res 115:117–141
Semba K, Reiner PB, McGeer EG, Fibiger HC (1988) Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat. J Comp Neurol 267:433–453
Semkova I, Krieglstein J (1999) Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Brain Res Rev 30:176–188
Semkova I, Schilling M, Henrich-Noack P, Rami A, Krieglstein J (1996) Clenbuterol protects mouse cerebral cortex and rat hippocampus from ischemic damage and attenuates glutamate neurotoxicity in cultured hippocampal neurons by induction of NGF. Brain Res 717:44–54
Seo J, Kim S, Kim H, Park CH, Jeong S, Lee J, Choi SH, Chang K, Rah J, Koo J, Kim E, Suh Y (2001) Effects of nicotine on APP secretion and Abeta- or CT(105)-induced toxicity. Biol Psychiatry 49:240–247
Seshadri S, Wolf PA (2007) Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study. Lancet Neurol 6:1106–1114
Sessler FM, Hsu FC, Felder TN, Zhai J, Lin RC, Wieland SJ, Kosobud AE (1998) Effects of ethanol on rat somatosensory cortical neurons. Brain Res 804:266–274
Shaffer SW, Harrison AL (2007) Aging of the somatosensory system: a translational perspective. Phys Ther 87:193–207
Shea SD, Katz LC, Mooney R (2008) Noradrenergic induction of odor-specific neural habituation and olfactory memories. J Neurosci 28:10711–10719
Shen J, Wu J (2015) Nicotinic Cholinergic Mechanisms in Alzheimer’s Disease. Int Rev Neurobiol 124:275–292
Shimohama S, Kihara T (2001) Nicotinic receptor-mediated protection against beta-amyloid neurotoxicity. Biol Psychiatry 49:233–239
Shipley MT, Halloran FJ, de la Torre J (1985) Surprisingly rich projection from locus coeruleus to the olfactory bulb in the rat. Brain Res 329:294–299
Sidhu MK, Stretton J, Winston GP, Bonelli S, Centeno M, Vollmar C, Symms M, Thompson PJ, Koepp MJ, Duncan JS (2013) A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy. Brain 136:1868–1888
Sigurdsson EM (2008) Immunotherapy targeting pathological tau protein in Alzheimer’s disease and related tauopathies. J Alzheimers Dis 15:157–168
Sima AA, Zhang W (2014) Mechanisms of diabetic neuropathy: axon dysfunction. Handb Clin Neurol 126:429–442
Simpson KL, Waterhouse BD, Lin RC (2006) Characterization of neurochemically specific projections from the locus coeruleus with respect to somatosensory-related barrels. Anat Rec A Discov Mol Cell Evol Biol 288:166–173
Sims NR, Anderson MF (2002) Mitochondrial contributions to tissue damage in stroke. Neurochem Int 40:511–512
Sloane JA, Hollander W, Moss MB, Rosene DL, Abraham CR (1999) Increased microglial activation and protein nitration in white matter of the aging monkey. Neurobiol Aging 20:395–405
Smith DE, Roberts J, Gage FH, Tuszynski MH (1999) Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc Natl Acad Sci USA 96:10893–10898
Smith DE, Rapp PR, McKay HM, Roberts JA, Tuszynski MH (2004) Memory impairment in aged primates is associated with focal death of cortical neurons and atrophy of subcortical neurons. J Neurosci 24:4373–4381
Snow PJ, Andre P, Pompeiano O (1999) Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin. Arch Ital Biol 137:1–28
Sokoloff L (1989) Circulation and energy metabolism of the brain. In: Segal G, Agranoff B, Albers RW, Molinoff P (eds) Basic neurochemistry. Raven, New York, pp 565–590
Solenski NJ, diPierro CG, Trimmer PA, Kwan AL, Helm GA (2002) Ultrastructural changes of neuronal mitochondria after transient and permanent cerebral ischemia. Stroke 33:816–824
Solfrizzi V, Scafato E, Capurso C, D’Introno A, Colacicco AM, Frisardi V, Vendemiale G, Baldereschi M, Crepaldi G, Di Carlo A, Galluzzo L, Gandin C, Inzitari D, Maggi S, Capurso A, Panza F et al (2010) Metabolic syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Ageing. J Neurol Neurosurg Psychiatry 81:433–440
Solfrizzi V, Scafato E, Capurso C, D’Introno A, Colacicco AM, Frisardi V, Vendemiale G, Baldereschi M, Crepaldi G, Di Carlo A, Galluzzo L, Gandin C, Inzitari D, Maggi S, Capurso A, Panza F (2011) Metabolic syndrome, mild cognitive impairment, and progression to dementia. The Italian Longitudinal Study on Aging. Neurobiol Aging 32:1932–1941
Sorg O, Magistretti PJ (1991) Characterization of the glycogenolysis elicited by vasoactive intestinal peptide, noradrenaline and adenosine in primary cultures of mouse cerebral cortical astrocytes. Brain Res 563:227–233
Srinivasan J, Schmidt WJ (2003) Potentiation of parkinsonian symptoms by depletion of locus coeruleus noradrenaline in 6-hydroxydopamine-induced partial degeneration of substantia nigra in rats. Eur J Neurosci 17:2586–2592
Steriade M (1997) Synchronized activities of coupled oscillators in the cerebral cortex and thalamus at different levels of vigilance. Cereb Cortex 7:583–604
Steriade M, Datta S, Paré D, Oakson G, Curró Dossi RC (1990) Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci 10:2541–2559
Stewart WF, Kawas C, Corrada M, Metter EJ (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48:626–632
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 103:10041–10045
Stranahan AM (2010) Mattson MP (2010) Selective vulnerability of neurons in layer II of the entorhinal cortex during aging and Alzheimer’s disease. Neural Plast 2010:108190
Strouse AL, Hall JW 3rd, Burger MC (1995) Central auditory processing in Alzheimer’s disease. Ear Hear 16:230–238
Su JH, Cummings BJ, Cotman CW (1996a) Plaque biogenesis in brain aging and Alzheimer’s disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments. Brain Res 739:79–87
Su JH, Cummings BJ, Cotman CW (1996b) Plaque biogenesis in brain aging and Alzheimer’s disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments. Brain Res 739:79–87
Sullivan EV, Pfefferbaum A (2006) Diffusion tensor imaging and aging. Neurosci Biobehav Rev 30:749–761
Sullivan EV, Pfefferbaum A (2007) Neuroradiological characterization of normal adult ageing. Brit J Radiol 80:S99–S108
Sullivan RM, Wilson DA, Lemon C, Gerhardt GA (1994) Bilateral 6-OHDA lesions of the locus coeruleus impair associative olfactory learning in newborn rats. Brain Res 643:306–309
Sullivan RM, Stackenwalt G, Nasr F, Lemon C, Wilson DA (2000) Association of an odor with activation of olfactory bulb noradrenergic beta-receptors or locus coeruleus stimulation is sufficient to produce learned approach responses to that odor in neonatal rats. Behav Neurosci 114:957–962
Sullivan EV, Adalsteinsson E, Hedehus M, Ju C, Moseley M, Lim KO, Pfefferbaum A (2001) Equivalent disruption of regional white matter microstructure in ageing healthy men and women. NeuroReport 12:99–104
Swan GE, DeCarli C, Miller BL, Reed T, Wolf PA, Jack LM, Carmelli D (1998) Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology 51:986–993
Sweatt JD (2004) Hippocampal function in cognition. Psychopharmacology 174:99–110
Szot P (2012) Common factors among Alzheimer’s disease, Parkinson’s disease, and epilepsy: possible role of the noradrenergic nervous system. Epilepsia 53:61–66
Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA (2006) Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer’s disease and dementia with Lewy bodies. J Neurosci 26:467–478
Szymusiak R (1995) Magnocellular nuclei of the basal forebrain: substrates of sleep and arousal regulation. Sleep 18:478–500
Takada H, Nagata K, Hirata Y, Satoh Y, Watahiki Y, Sugawara J, Yokoyama E, Kondoh Y, Shishido F, Inugami A et al (1992) Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography. Neurol Res 14:128–131
Takata N, Nagai T, Ozawa K, Oe Y, Mikoshiba K, Hirase H (2013) Cerebral blood flow modulation by Basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes. PLoS One 8:e66525
Takuwa H, Masamoto K, Yamazaki K, Kawaguchi H, Ikoma Y, Tajima Y, Obata T, Tomita Y, Suzuki N, Kanno I, Ito H (2013) Long-term adaptation of cerebral hemodynamic response to somatosensory stimulation during chronic hypoxia in awake mice. J Cereb Blood Flow Metab 33:774–779
Tatton WG, Greenwood CE, Verrier MC, Holland DP, Kwan MM, Biddle FE (1991) Different rates of age-related loss for four murine monoaminergic neuronal populations. Neurobiol Aging 12:543–556
Tay T, Wang JJ, Kifley A, Lindley R, Newall P, Mitchell P (2006) Sensory and cognitive association in older persons: findings from an older Australian population. Gerontology 52:386–394
Teipel S, Grothe MJ, Zhou J, Sepulcre J, Dyrba M, Sorg C, Babiloni C (2016) Measuring cortical connectivity in Alzheimer’s disease as a brain neural network pathology: toward clinical applications. J Int Neuropsychol Soc 22:138–163
Terasawa H, Hirai T, Ninomiya T, Ikeda Y, Ishijima T, Yajima T, Hamaue N, Nagase Y, Kang Y, Minami M (2002) Influence of tooth-loss and concomitant masticatory alterations on cholinergic neurons in rats: immunohistochemical and biochemical studies. Neurosci Res 43:373–379
Thomas T, Thomas G, McLendon C, Sutton T, Mullan M (1996) beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature (London) 380:168–171
Tomonaga M (1983) Neuropathology of the locus ceruleus: a semi-quantitative study. J Neurol 230:231–240
Topcuoglu MA, Aydin H, Saka E (2009) Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: effect of healthy aging. Neurosci Lett 452:17–22
Toussay X, Basu K, Lacoste B, Hamel E (2013) Locus coeruleus stimulation recruits a broad cortical neuronal network and increases cortical perfusion. J Neurosci 33:3390–3401
Traver S, Salthun-Lassalle B, Marien M, Hirsch EC, Colpaert F, Michel PP (2005) The neurotransmitter noradrenaline rescues septal cholinergic neurons in culture from degeneration caused by low-level oxidative stress. Mol Pharmacol 67:1882–1891
Troadec JD, Marien M, Darios F, Hartmann A, Ruberg M, Colpaert F, Michel PP (2001) Noradrenaline provides long-term protection to dopaminergic neurons by reducing oxidative stress. J Neurochem 79:200–210
Truchet B, Chaillan FA, Soumireu-Mourat B, Roman FS (2002) Learning and memory of cue-reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex. Hippocampus 12:600–608
Tsai YJ, Ramar K, Liang YJ, Chiu PH, Powell N, Chi CY, Lung TC, Wen-Yang Lin W, Tseng PJ, Wu MY, Chien KC, Weaver EM, Lee FP, Lin CM, Chen KC, Chiang RP (2013) Peripheral neuropathology of the upper airway in obstructive sleep apnea syndrome. Sleep Med Rev 17:161–168
Tsukada H, Yamazaki S, Noda A, Inoue T, Matsuoka N, Kakiuchi T, Nishiyama S, Nishimura S (1999) FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys. Brain Res 832:118–123
Uchida S, Hotta H (2009) Cerebral cortical vasodilatation mediated by nicotinic cholinergic receptors: effects of old age and of chronic nicotine exposure. Biol Pharm Bull 32:341–344
Uchida S, Kagitani F, Nakayama H, Sato A (1997) Effect of stimulation of nicotinic cholinergic receptors on cortical cerebral blood flow and changes in the effect during aging in anesthetized rats. Neurosci Lett 228:203–206
Uchida S, Suzuki A, Kagitani F, Hotta H (2000) Effects of age on cholinergic vasodilation of cortical cerebral blood vessels in rats. Neurosci Lett 294:109–112
Uluc K, Isak B, Borucu D, Temucin CM, Cetinkaya Y, Koytak PK, Tanridag T, Us O (2008) Medial plantar and dorsal sural nerve conduction studies increase the sensitivity in the detection of neuropathy in diabetic patients. Clin Neurophysiol 119:880–885
Usher M, Cohen JD, Servan-Schreiber D, Rajkowski J, Aston-Jones G (1999) The role of locus coeruleus in the regulation of cognitive performance. Science 283:549–554
Vandenbulcke M, Janssens J (1999) Acute axonal polyneuropathy in chronic alcoholism and malnutrition. Acta Neurol Belg 99:198–201
Varma AR, Adams W, Lloyd JJ, Carson KJ, Snowden JS, Testa HJ, Jackson A, Neary D (2002) Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer’s disease, frontotemporal dementia and vascular dementia. Acta Neurol Scand 105:261–269
Varrone A, Pappatà S, Caracò C, Soricelli A, Milan G, Quarantelli M, Alfano B, Postiglione A, Salvatore M (2002) Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer’s disease highlights the involvement of different cortical networks. Eur J Nucl Med Mol Imaging 29:1447–1454
Vasavada MM, Wang J, Eslinger PJ, Gill DJ, Sun X, Karunanayaka P, Yang QX (2015) Olfactory cortex degeneration in Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 45:947–958
Veasey SC, Davis C, Zhan G, Hsu YJ, Fenik P, Pratico D, Gow AJ (2004) Intermittent hypoxia in mice: protracted hypersomnolence and basal forebrain redox alterations. Sleep 27:194–201
Venero JL, Knüsel B, Beck KD, Hefti F (1994) Expression of neurotrophin and trk receptor genes in adult rats with fimbria transections: effect of intraventricular nerve growth factor and brain-derived neurotrophic factor administration. Neuroscience 59:797–815
Verdú E, Ceballos D, Vilches JJ, Navarro X (2000) Influence of aging on peripheral nerve function and regeneration. J Peripher Nerv Syst 5:191–208
Vertes RP (1988) Brainstem afferents to the basal forebrain in the rat. Neuroscience 24:907–935
Vinogradova OS, Brazhnik ES, Kichigina VF, Stafekhina VS (1996) Modulation of the reaction of hippocampal neurons to sensory stimuli by cholinergic substances. Neurosci Behav Physiol 26:113–124
Vuono IM, Zanoteli E, de Oliveira AS, Fujita RR, Pignatari SS, Pizarro GU, de Cássia Pradelle-Hallinan ML, Moreira GA (2007) Histological analysis of palatopharyngeal muscle from children with snoring and obstructive sleep apnea syndrome. Int J Pediatr Otorhinolaryngol 71:283–290
Walling SG, Harley CW (2004) Locus ceruleus activation initiates delayed synaptic potentiation of perforant path input to the dentate gyrus in awake rats: a novel beta-adrenergic- and protein synthesis-dependent mammalian plasticity mechanism. J Neurosci 24:598–604
Wang J, Eslinger PJ, Smith MB, Yang QX (2005) Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci 60:510–514
Wang J, Eslinger PJ, Doty RL, Zimmerman EK, Grunfeld R, Sun X, Meadowcroft MD, Connor JR, Price JL, Smith MB, Yang QX (2010) Olfactory deficit detected by fMRI in early Alzheimer’s disease. Brain Res 1357:184–194
Wang Z, Jia X, Liang P, Qi Z, Yang Y, Zhou W, Li K (2012) Changes in thalamus connectivity in mild cognitive impairment: evidence from resting state fMRI. Eur J Radiol 81:277–285
Waterhouse BD, Azizi SA, Burne RA, Woodward DJ (1990) Modulation of rat cortical area 17 neuronal responses to moving visual stimuli during norepinephrine and serotonin microiontophoresis. Brain Res 514:276–292
Waterhouse BD, Moises HC, Woodward DJ (1998) Phasic activation of the locus coeruleus enhances responses of primary sensory cortical neurons to peripheral receptive field stimulation. Brain Res 790:33–44
Weinshenker D (2008) Functional consequences of locus coeruleus degeneration in Alzheimer’s disease. Curr Alzheimer Res 5:342–345
Weintraub D, Mavandadi S, Mamikonyan E, Siderowf AD, Duda JE, Hurtig HI, Colcher A, Horn SS, Nazem S, Ten Have TR, Stern MB (2010) Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology 75:448–455
Weintraub S, Wicklund AH, Salmon DP (2012) The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med 2:a006171
Weldon DT, Rogers SD, Ghilardi JR, Finke MP, Cleary JP, O’Hare E, Esler WP, Maggio JE, Mantyh PW (1998) Fibrillar β-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo. J Neurosci 18:2161–2173
Wenk G, Hepler D, Olton D (1984) Behavior alters the uptake of [3H]choline into acetylcholinergic neurons of the nucleus basalis magnocellularis and medial septal area. Behav Brain Res 13:129–138
Wes PD, Easton A, Corradi J, Barten DM, Devidze N, DeCarr LB, Truong A, He A, Barrezueta NX, Polson C, Bourin C, Flynn ME, Keenan S, Lidge R, Meredith J, Natale J, Sankaranarayanan S, Cadelina GW, Albright CF, Cacace AM (2014) Tau overexpression impacts neuroinflammation gene expression network perturbed in Alzheimer’s disease. PLoS One 9:e106050
Wesson DW, Borkowski AH, Landreth GE, Nixon RA, Levy E, Wilson DA (2011) Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer’s β-amyloidosis mouse model. J Neurosci 31:15962–15971
White HL, Scates PW (1990) Acetyl-l-carnitine as a precursor of acetylcholine. Neurochem Res 15:597–601
Whitmer RA, Gunderson EP, Quesenberry CP Jr, Zhou J, Yaffe K (2007) Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 4:103–109
Whittaker JR, Driver ID, Bright MG, Murphy K (2016) The absolute CBF response to activation is preserved during elevated perfusion: implications for neurovascular coupling measures. Neuroimage 125:198–207
Wilcock GK, Esiri MM, Bowen DM, Hughes AO (1988) The differential involvement of subcortical nuclei in senile dementia of Alzheimer’s type. J Neurol Neurosurg Psychiatry 51:842–849
Winkler S, Garg AK, Mekayarajjananonth T, Bakaeen LG, Khan E (1999) Depressed taste and smell in geriatric patients. J Am Dent Assoc 130:1759–1765
Winters BD, Bussey TJ (2005) Removal of cholinergic input to perirhinal cortex disrupts object recognition but not spatial working memory in the rat. Eur J Neurosci 21:2263–2270
Winton MJ, Lee EB, Sun E, Wong MM, Leight S, Zhang B, Trojanowski JQ, Lee VM (2011) Intraneuronal APP, not free Aβ peptides in 3xTg-AD mice: implications for tau versus Aβ-mediated Alzheimer neurodegeneration. J Neurosci 31:7691–7699
Wirth S, Yanike M, Frank LM, Smith AC, Brown EN, Suzuki WA (2003) Single neurons in the monkey hippocampus and learning of new associations. Science 300:1578–1581
Witter MP, Room P, Groenewegen HJ, Lohman AH (1986) Connections of the parahippocampal cortex in the cat. V. Intrinsic connections; comments on input/output connections with the hippocampus. J Comp Neurol 252:78–94
Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AH (1989) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog Neurobiol 33:161–253
Wöhrle JC, Spengos K, Steinke W, Goebel HH, Hennerici M (1998) Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain-Barré syndrome. Arch Neurol 55:1329–1334
Wood KM, Edwards JD, Clay OJ, Wadley VG, Roenker DL, Ball KK (2005) Sensory and cognitive factors influencing functional ability in older adults. Gerontology 51:131–141
Woodson BT, Garancis JC, Toohill RJ (1991) Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 101:1318–1322
Woolsey TA, Rovainen CM, Cox SB, Henegar MH, Liang GE, Liu D, Moskalenko YE, Sui J, Wei L (1996) Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. Cereb Cortex 6:647–660
Wu ST, Chiu CJ (2016) Age-related trajectories of memory function in middle-aged and older adults with and without hearing impairment. Neuroepidemiology 46:282–289
Wu CF, Bertorelli R, Sacconi M, Pepeu G, Consolo S (1988) Decrease of brain acetylcholine release in aging freely-moving rats detected by microdialysis. Neurobiol Aging 9:357–361
Wu N, Rao X, Gao Y, Wang J, Xu F (2013) Amyloid-β deposition and olfactory dysfunction in an Alzheimer’s disease model. J Alzheimers Dis 37:699–712
Xu W, Chi L, Row BW, Xu R, Ke Y, Xu B, Luo C, Kheirandish L, Gozal D, Liu R (2004) Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience 126:313–323
Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292:2237–2242
Yamada Y, Denkinger MD, Onder G, Henrard JC, van der Roest HG, Finne-Soveri H, Richter T, Vlachova M, Bernabei R, Topinkova E (2016) Dual sensory impairment and cognitive decline: the results from the shelter study. J Gerontol A Biol Sci Med Sci 71:117–123
Yao N, Wu Y, Zhou Y, Ju L, Liu Y, Ju R, Duan D, Xu Q (2015) Lesion of the locus coeruleus aggravates dopaminergic neuron degeneration by modulating microglial function in mouse models of Parkinson's disease. Brain Res 1625:255–274
Yekta SS, Smeets R, Stein JM, Ellrich J (2010) Assessment of trigeminal nerve functions by quantitative sensory testing in patients and healthy volunteers. J Oral Maxillofac Surg 68:2437–2451
Yonelinas AP, Otten LJ, Shaw KN, Rugg MD (2005) Separating the brain regions involved in recollection and familiarity in recognition memory. J Neurosci 25:3002–3008
Yoon JH, Kim M, Moon SY, Yong SW, Hong JM (2015) Olfactory function and neuropsychological profile to differentiate dementia with Lewy bodies from Alzheimer’s disease in patients with mild cognitive impairment: a 5-year follow-up study. J Neurol Sci 355:174–179
Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351
Yu S, Wang Y, Li X, Zhou Y, Leventhal AG (2006) Functional degradation of extrastriate visual cortex in senescent rhesus monkeys. Neuroscience 140:1023–1029
Zaborszky L, Cullinan WE, Braun A (1991) Afferents to basal forebrain cholinergic projection neurons: an update. Adv Exp Med Biol 295:43–100
Zaborszky L, Gaykema RP, Swanson DJ, Cullinan WE (1997) Cortical input to the basal forebrain. Neuroscience 79:1051–1078
Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60:337–341
Zelcer I, Cohen H, Richter-Levin G, Lebiosn T, Grossberger T, Barkai E (2006) A cellular correlate of learning-induced metaplasticity in the hippocampus. Cereb Cortex 16:460–468
Zeng HL, Rao X, Zhang LK et al (2014) Quantitative proteomics reveals olfactory input-dependent alterations in the mouse olfactory bulb proteome. J Proteomics 109:125–142
Zerari-Mailly F, Pinganaud G, Dauvergne C, Buisseret P, Buisseret-Delmas C (2001) Trigemino-reticulo-facial and trigemino-reticulo-hypoglossal pathways in the rat. J Comp Neurol 429:80–83
Zhan G, Fenik P, Pratico D, Veasey SC (2005a) Inducible nitric oxide synthase in long-term intermittent hypoxia: hypersomnolence and brain injury. Am J Respir Crit Care Med 171:1414–1420
Zhan G, Serrano F, Hsu R, Kong L, Fenik P, Pratico D, Klann E, Veasey SC (2005b) NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am J Respir Crit Care Med 172:921–929
Zhang F, Eckman C, Younkin S, Hsiao KK, Iadecola C (1997) Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein. J Neurosci 17:7655–7661
Zhang J, Wang X, Wang Y, Fu Y, Liang Z, Ma Y, Leventhal AG (2008) Spatial and temporal sensitivity degradation of primary visual cortical cells in senescent rhesus monkeys. Eur J Neurosci 28:201–207
Zhang J, Zhu Y, Zhan G, Fenik P, Panossian L, Wang MM, Reid S, Lai D, Davis JG, Baur JA, Veasey S (2014) Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons. J Neurosci 34:4418–4431
Zhang N, Ye N, Chen Y, Guo X, Sun G, Sun Y (2016) The relationship between snoring and left ventricular hypertrophy of China: a cross-sectional study. BMC Cardiovasc Disord 16:15
Zhao K, Ippolito G, Wang L, Price V, Kim MH, Cornwell G, Fulenchek S, Breen GA, Goux WJ, D’Mello SR (2010) Neuron-selective toxicity of tau peptide in a cell culture model of neurodegenerative tauopathy: essential role for aggregation in neurotoxicity. J Neurosci Res 88:3399–3413
Zhao S, Tian H, Ma L, Yuan Y, Yu CR, Ma M (2013) Activity-dependent modulation of odorant receptor gene expression in the mouse olfactory epithelium. PLoS One 8:e69862
Zhou B, Liu Y, Zhang Z, An N, Yao H, Wang P, Wang L, Zhang X, Jiang T (2013) Impaired functional connectivity of the thalamus in Alzheimer’s disease and mild cognitive impairment: a resting-state fMRI study. Curr Alzheimer Res 10:754–766
Zhu Y, Fenik P, Zhan G, Mazza E, Kelz M, Aston-Jones G, Veasey SC (2007) Selective loss of catecholaminergic wake active neurons in a murine sleep apnea model. J Neurosci 27:10060–10071
Zhu Y, Fenik P, Zhan G, Xin R, Veasey SC (2015) Degeneration in Arousal Neurons in Chronic Sleep Disruption Modeling Sleep Apnea. Front Neurol 6:109
Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, Brüggemann J, Strom A, Peschel S, Köhler B, Stachs O, Guthoff RF, Roden M (2014) Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 63:2454–2463
Zilka N, Stozicka Z, Kovac A, Pilipcinec E, Bugos O, Novak M (2009) Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy. J Neuroimmunol 209:16–25
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Daulatzai, M.A. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease. Neurotox Res 30, 295–337 (2016). https://doi.org/10.1007/s12640-016-9643-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-016-9643-3