Neuropsychology Review

, Volume 24, Issue 3, pp 300–312

The Relevance of Beta-Amyloid on Markers of Alzheimer’s Disease in Clinically Normal Individuals and Factors That Influence These Associations

Review

Abstract

Aberrant accumulation of beta-amyloid (Aβ) is thought to be an early event in a biological cascade that eventually leads to Alzheimer’s disease (AD). Along these lines, many clinically normal (CN) older individuals have evidence of beta-amyloid (Aβ) accumulation, which may be indicative of preclinical AD. However, relationships between Aβ and “downstream” AD markers are often inconsistent across studies. These inconsistencies may be due to the presence of other age-related processes that also influence AD markers, as well as additional risk factors that interact with Aβ to influence downstream changes. For instance, it is possible that the effect of Aβ is modified by neurodegeneration, genetics, sex-differences and cognitive reserve. Thus, a multivariate approach to determining risk of AD within CN participants may be more appropriate than reliance on Aβ status alone. An understanding of how additional risk factors interact with Aβ to influence an individual’s trajectory towards AD is essential for characterizing preclinical AD and has implications for prevention trials.

Keywords

Aging Preclinical Alzheimer’s disease Beta-amyloid Amyloid PET imaging Resilience 

References

  1. Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., et al. (2008). Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology, 65, 1509–1517.PubMedCentralPubMedGoogle Scholar
  2. Alexopoulos, P., Richter-Schmidinger, T., Horn, M., Maus, S., Reichel, M., Sidiropoulos, C., et al. (2011). Hippocampal volume differences between healthy young apolipoprotein E epsilon2 and epsilon4 carriers. Journal of Alzheimer's Disease, 26, 207–210.PubMedGoogle Scholar
  3. Alz.org. (2014). Alzheimer’s Disease Facts and Figures.Google Scholar
  4. Amir, E., Freedman, O. C., Seruga, B., & Evans, D. G. (2010). Assessing women at high risk of breast cancer: a review of risk assessment models. Journal of the National Cancer Institute, 102, 680–691.PubMedGoogle Scholar
  5. Andrews-Hanna, J. R., Reidler, J. S., Sepulcre, J., Poulin, R., & Buckner, R. L. (2010). Functional-anatomic fractionation of the brain's default network. Neuron, 65, 550–562.PubMedCentralPubMedGoogle Scholar
  6. Barker, W. W., Luis, C. A., Kashuba, A., Luis, M., Harwood, D. G., Loewenstein, D., et al. (2002). Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Disease and Associated Disorders, 16, 203–212.PubMedGoogle Scholar
  7. Becker, J. A., Hedden, T., Carmasin, J., Maye, J., Rentz, D. M., Putcha, D., et al. (2011). Amyloid-beta associated cortical thinning in clinically normal elderly. Annals of Neurology, 69, 1032–1042.PubMedCentralPubMedGoogle Scholar
  8. Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., et al. (2006). Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology, 66, 1837–1844.PubMedGoogle Scholar
  9. Bentahir, M., Nyabi, O., Verhamme, J., Tolia, A., Horre, K., Wiltfang, J., et al. (2006). Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. Journal of Neurochemistry, 96, 732–742.PubMedGoogle Scholar
  10. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18, 351–357.PubMedGoogle Scholar
  11. Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1–38.PubMedGoogle Scholar
  12. Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., et al. (2009). Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. Journal of Neuroscience, 29, 1860–1873.PubMedCentralPubMedGoogle Scholar
  13. Buckner, R. L., & Vincent, J. L. (2007). Unrest at rest: default activity and spontaneous network correlations. NeuroImage, 37, 1091–1096. discussion 1097–9.PubMedGoogle Scholar
  14. Cabeza, R., Anderson, N. D., Locantore, J. K., & McIntosh, A. R. (2002). Aging gracefully: compensatory brain activity in high-performing older adults. NeuroImage, 17, 1394–1402.PubMedGoogle Scholar
  15. Carter, C. L., Resnick, E. M., Mallampalli, M., & Kalbarczyk, A. (2012). Sex and gender differences in Alzheimer's disease: recommendations for future research. Journal of Women's Health (2002), 21, 1018–1023.Google Scholar
  16. Chetelat, G., Villemagne, V. L., Pike, K. E., Baron, J. C., Bourgeat, P., Jones, G., et al. (2010). Larger temporal volume in elderly with high versus low beta-amyloid deposition. Brain, 133, 3349–3358.PubMedGoogle Scholar
  17. Chetelat, G., Villemagne, V. L., Villain, N., Jones, G., Ellis, K. A., Ames, D., et al. (2012). Accelerated cortical atrophy in cognitively normal elderly with high beta-amyloid deposition. Neurology, 78, 477–484.PubMedGoogle Scholar
  18. Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., et al. (2005). Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron, 48, 913–922.PubMedGoogle Scholar
  19. Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., et al. (1992). Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature, 360, 672–674.PubMedGoogle Scholar
  20. Costa, D. A., Cracchiolo, J. R., Bachstetter, A. D., Hughes, T. F., Bales, K. R., Paul, S. M., et al. (2007). Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiology of Aging, 28, 831–844.PubMedGoogle Scholar
  21. Damoiseaux, J. S., Prater, K. E., Miller, B. L., & Greicius, M. D. (2012a). Functional connectivity tracks clinical deterioration in Alzheimer's disease. Neurobiology of Aging, 33, 828 e19–828 e30.Google Scholar
  22. Damoiseaux, J. S., Seeley, W. W., Zhou, J., Shirer, W. R., Coppola, G., Karydas, A., et al. (2012b). Gender modulates the APOE epsilon4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels. Journal of Neuroscience, 32, 8254–8262.PubMedCentralPubMedGoogle Scholar
  23. Daselaar, S. M., Prince, S. E., & Cabeza, R. (2004). When less means more: deactivations during encoding that predict subsequent memory. NeuroImage, 23, 921–927.PubMedGoogle Scholar
  24. Davies, C. A., Mann, D. M., Sumpter, P. Q., & Yates, P. O. (1987). A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. Journal of Neurological Sciences, 78, 151–164.Google Scholar
  25. de Chastelaine, M., Wang, T. H., Minton, B., Muftuler, L. T., & Rugg, M. D. (2011). The effects of Age, memory performance, and callosal integrity on the neural correlates of successful associative encoding. Cerebral Cortex, 21, 2166–2176.PubMedCentralPubMedGoogle Scholar
  26. DeCarli, C., Murphy, D. G., Tranh, M., Grady, C. L., Haxby, J. V., Gillette, J. A., et al. (1995). The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology, 45, 2077–2084.PubMedGoogle Scholar
  27. Desikan, R. S., McEvoy, L. K., Thompson, W. K., Holland, D., Brewer, J. B., Aisen, P. S., et al. (2012). Amyloid-beta–associated clinical decline occurs only in the presence of elevated P-tau. Archives of Neurology, 69, 709–713.PubMedCentralPubMedGoogle Scholar
  28. Desikan, R. S., McEvoy, L. K., Thompson, W. K., Holland, D., Roddey, J. C., Blennow, K., et al. (2011). Amyloid-beta associated volume loss occurs only in the presence of phospho-tau. Annals of Neurology, 70, 657–661.PubMedCentralPubMedGoogle Scholar
  29. Dickerson, B. C., Bakkour, A., Salat, D. H., Feczko, E., Pacheco, J., Greve, D. N., et al. (2009). The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cerebral Cortex, 19, 497–510.PubMedCentralPubMedGoogle Scholar
  30. Dodart, J. C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., et al. (2002). Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nature Neuroscience, 5, 452–457.PubMedGoogle Scholar
  31. Doraiswamy, P. M., Sperling, R. A., Coleman, R. E., Johnson, K. A., Reiman, E. M., Davis, M. D., et al. (2012). Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study. Neurology, 79, 1636–1644.PubMedCentralPubMedGoogle Scholar
  32. Dore, V., Villemagne, V. L., Bourgeat, P., Fripp, J., Acosta, O., Chetelat, G., et al. (2013). Cross-sectional and longitudinal analysis of the relationship between Abeta deposition, cortical thickness, and memory in cognitively unimpaired individuals and in Alzheimer disease. JAMA Neurology, 70, 903–911.PubMedGoogle Scholar
  33. Duara, R., Barker, W. W., Lopez-Alberola, R., Loewenstein, D. A., Grau, L. B., Gilchrist, D., et al. (1996). Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset. Neurology, 46, 1575–1579.PubMedGoogle Scholar
  34. Eberling, J. L., Wu, C., Tong-Turnbeaugh, R., & Jagust, W. J. (2004). Estrogen- and tamoxifen-associated effects on brain structure and function. NeuroImage, 21, 364–371.PubMedGoogle Scholar
  35. Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257–269.PubMedGoogle Scholar
  36. Fagan, A. M., Mintun, M. A., Mach, R. H., Lee, S. Y., Dence, C. S., Shah, A. R., et al. (2006). Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Annals of Neurology, 59, 512–519.PubMedGoogle Scholar
  37. Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., et al. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA, 278, 1349–1356.PubMedGoogle Scholar
  38. Fjell, A. M., McEvoy, L., Holland, D., Dale, A. M., & Walhovd, K. B. (2013). Brain changes in older adults at very low risk for Alzheimer's disease. Journal of Neuroscience, 33, 8237–8242.PubMedCentralPubMedGoogle Scholar
  39. Fjell, A.M., McEvoy, L., Holland, D., Dale, A.M., Walhovd, K.B. (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus. Prog Neurobiol.Google Scholar
  40. Fjell, A. M., Walhovd, K. B., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., et al. (2009). One-year brain atrophy evident in healthy aging. Journal of Neuroscience, 29, 15223–15231.PubMedCentralPubMedGoogle Scholar
  41. Fox, M. D., & Raichle, M. E. (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Review Neuroscience, 8, 700–711.Google Scholar
  42. Grober, E., Hall, C. B., Lipton, R. B., Zonderman, A. B., Resnick, S. M., & Kawas, C. (2008). Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease. Journal of International Neuropsychological Society, 14, 266–278.Google Scholar
  43. Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 297, 353–356.PubMedGoogle Scholar
  44. Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013). Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology, 80, 1778–1783.PubMedCentralPubMedGoogle Scholar
  45. Hedden, T., Van Dijk, K. R., Becker, J. A., Mehta, A., Sperling, R. A., Johnson, K. A., et al. (2009). Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. Journal of Neuroscience, 29, 12686–12694.PubMedCentralPubMedGoogle Scholar
  46. Hedden, T., Van Dijk, K.R., Shire, E.H., Sperling, R.A., Johnson, K.A., Buckner, R.L. (2011). Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology. Cereb Cortex.Google Scholar
  47. Holland, D., Desikan, R. S., Dale, A. M., & McEvoy, L. K. (2013). Higher rates of decline for women and apolipoprotein E epsilon4 carriers. AJNR - American Journal of Neuroradiology, 34, 2287–2293.PubMedCentralPubMedGoogle Scholar
  48. Huijbers, W., Schultz, A. P., Vannini, P., McLaren, D. G., Wigman, S. E., Ward, A. M., et al. (2013). The encoding/retrieval flip: interactions between memory performance and memory stage and relationship to intrinsic cortical networks. Journal of Cognitive Neuroscience, 25, 1163–1179.PubMedCentralPubMedGoogle Scholar
  49. Ittner, L. M., & Gotz, J. (2011). Amyloid-beta and tau–a toxic pas de deux in Alzheimer's disease. Nature Review Neuroscience, 12, 65–72.Google Scholar
  50. Jack, C. R., Jr., Dickson, D. W., Parisi, J. E., Xu, Y. C., Cha, R. H., O'Brien, P. C., et al. (2002). Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology, 58, 750–757.PubMedCentralPubMedGoogle Scholar
  51. Jack, C. R., Jr., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., et al. (2013a). Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurology, 12, 207–216.PubMedCentralGoogle Scholar
  52. Jack, C. R., Jr., Knopman, D. S., Weigand, S. D., Wiste, H. J., Vemuri, P., Lowe, V., et al. (2012). An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Annals of Neurology, 71, 765–775.PubMedCentralPubMedGoogle Scholar
  53. Jack, C.R., Jr., Wiste, H.J., Knopman, D.S., Vemuri, P., Mielke, M.M., Weigand, S.D., et al. (2014). Rates of beta-amyloid accumulation are independent of hippocampal neurodegeneration. Neurology.Google Scholar
  54. Jack, C. R., Jr., Wiste, H. J., Weigand, S. D., Knopman, D. S., Lowe, V., Vemuri, P., et al. (2013b). Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. Neurology, 81, 1732–1740.PubMedCentralPubMedGoogle Scholar
  55. Jagust, W. (2013). Vulnerable neural systems and the borderland of brain aging and neurodegeneration. Neuron, 77, 219–234.PubMedCentralPubMedGoogle Scholar
  56. Jagust, W. J., & Landau, S. M. (2012). Apolipoprotein E, not fibrillar beta-amyloid, reduces cerebral glucose metabolism in normal aging. Journal of Neuroscience, 32, 18227–18233.PubMedCentralPubMedGoogle Scholar
  57. Jagust, W. J., Landau, S. M., Shaw, L. M., Trojanowski, J. Q., Koeppe, R. A., Reiman, E. M., et al. (2009). Relationships between biomarkers in aging and dementia. Neurology, 73, 1193–1199.PubMedCentralPubMedGoogle Scholar
  58. Jagust, W. J., & Mormino, E. C. (2011). Lifespan Brain Activity, β-Amyloid, and Alzheimer's Disease. Trends in Cognitive Science, 15, 520–526.Google Scholar
  59. Jicha, G. A., Parisi, J. E., Dickson, D. W., Johnson, K., Cha, R., Ivnik, R. J., et al. (2006). Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Archives of Neurology, 63, 674–681.PubMedGoogle Scholar
  60. Johnson, S. C., Christian, B. T., Okonkwo, O. C., Oh, J. M., Harding, S., Xu, G., et al. (2014). Amyloid burden and neural function in people at risk for Alzheimer's Disease. Neurobiology of Aging, 35, 576–584.PubMedGoogle Scholar
  61. Kantarci, K., Lowe, V., Przybelski, S. A., Weigand, S. D., Senjem, M. L., Ivnik, R. J., et al. (2012). APOE modifies the association between Abeta load and cognition in cognitively normal older adults. Neurology, 78, 232–240.PubMedCentralPubMedGoogle Scholar
  62. Kennedy, K. M., Rodrigue, K. M., Devous, M. D., Sr., Hebrank, A. C., Bischof, G. N., & Park, D. C. (2012). Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan. NeuroImage, 62, 1–8.PubMedCentralPubMedGoogle Scholar
  63. Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., et al. (2004). Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Annals of Neurology, 55, 306–319.PubMedGoogle Scholar
  64. Knopman, D.S., Jack, C.R., Jr., Wiste, H.J., Lundt, E.S., Weigand, S.D., Vemuri, P., et al. (2014). F-fluorodeoxyglucose positron emission tomography, aging, and apolipoprotein E genotype in cognitively normal persons. Neurobiol Aging.Google Scholar
  65. Knopman, D. S., Jack, C. R., Jr., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V., et al. (2012). Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology, 78, 1576–1582.PubMedCentralPubMedGoogle Scholar
  66. Knopman, D. S., Jack, C. R., Jr., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V. J., et al. (2013). Selective worsening of brain injury biomarker abnormalities in cognitively normal elderly persons with beta-amyloidosis. JAMA Neurology, 70, 1030–1038.PubMedGoogle Scholar
  67. Kok, E., Haikonen, S., Luoto, T., Huhtala, H., Goebeler, S., Haapasalo, H., et al. (2009). Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Annals of Neurology, 65, 650–657.PubMedGoogle Scholar
  68. Landau, S. M., Marks, S. M., Mormino, E. C., Rabinovici, G. D., Oh, H., O'Neil, J. P., et al. (2012a). Association of lifetime cognitive engagement and low beta-amyloid deposition. Archives of Neurology, 69, 623–629.PubMedCentralPubMedGoogle Scholar
  69. Landau, S. M., Mintun, M. A., Joshi, A. D., Koeppe, R. A., Petersen, R. C., Aisen, P. S., et al. (2012b). Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Annals of Neurology, 72, 578–586.PubMedCentralPubMedGoogle Scholar
  70. Li, S. C., Brehmer, Y., Shing, Y. L., Werkle-Bergner, M., & Lindenberger, U. (2006). Neuromodulation of associative and organizational plasticity across the life span: empirical evidence and neurocomputational modeling. Neuroscience and Biobehavioral Reviews, 30, 775–790.PubMedGoogle Scholar
  71. Lim, Y. Y., Maruff, P., Pietrzak, R. H., Ames, D., Ellis, K. A., Harrington, K., et al. (2013a). Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease. Brain, 137, 221–231.PubMedGoogle Scholar
  72. Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D., Pietrzak, R. H., Ellis, K. A., et al. (2013b). BDNF Val66Met, Abeta amyloid, and cognitive decline in preclinical Alzheimer's disease. Neurobiology of Aging, 34, 2457–2464.PubMedGoogle Scholar
  73. Logan, J. M., Sanders, A. L., Snyder, A. Z., Morris, J. C., & Buckner, R. L. (2002). Under-recruitment and nonselective recruitment: dissociable neural mechanisms associated with aging. Neuron, 33, 827–840.PubMedGoogle Scholar
  74. Lott, I. T., Head, E., Doran, E., & Busciglio, J. (2006). Beta-amyloid, oxidative stress and down syndrome. Current Alzheimer Research, 3, 521–528.PubMedGoogle Scholar
  75. Lupien, S. J., de Leon, M., de Santi, S., Convit, A., Tarshish, C., Nair, N. P., et al. (1998). Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nature Neuroscience, 1, 69–73.PubMedGoogle Scholar
  76. Mahley, R. W., & Huang, Y. (2012). Apolipoprotein e sets the stage: response to injury triggers neuropathology. Neuron, 76, 871–885.PubMedGoogle Scholar
  77. Marsland, A. L., Gianaros, P. J., Abramowitch, S. M., Manuck, S. B., & Hariri, A. R. (2008). Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biological Psychiatry, 64, 484–490.PubMedCentralPubMedGoogle Scholar
  78. Mathis, C. A., Kuller, L. H., Klunk, W. E., Snitz, B. E., Price, J. C., Weissfeld, L. A., et al. (2013). In vivo assessment of amyloid-beta deposition in nondemented very elderly subjects. Annals of Neurology, 73, 751–761.PubMedCentralPubMedGoogle Scholar
  79. Mattsson, N., Insel, P.S., Nosheny, R., Tosun, D., Trojanowski, J.Q., Shaw, L.M., et al. (2014). Emerging beta-Amyloid Pathology and Accelerated Cortical Atrophy. JAMA Neurol.Google Scholar
  80. Mormino, E.C., Betensky, R.A., Hedden, T., Schultz, A.P., Amariglio, R.E., Rentz, D.M., et al. (2014). Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal participants. JAMA Neurol.Google Scholar
  81. Mormino, E.C., Betensky, R.A., Hedden, T., Schultz, A.P., Ward, A., Huijbers, W., et al. (2014). Amyloid and APOE4 interact to influence short-term decline in preclinical Alzheimer’s disease. Neurology.Google Scholar
  82. Mormino, E.C., Brandel, M.G., Madison, C.M., Marks, S., Baker, S.L., Jagust, W.J. (2011a). Aβ deposition in aging is associated with increases in brain activation during successful memory encoding. Cerebral Cortex.Google Scholar
  83. Mormino, E. C., Kluth, J. T., Madison, C. M., Rabinovici, G. D., Baker, S. L., Miller, B. L., et al. (2009). Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain, 132, 1310–1323.PubMedCentralPubMedGoogle Scholar
  84. Mormino, E. C., Smiljic, A., Hayenga, A. O., Onami, S. H., Greicius, M. D., Rabinovici, G. D., et al. (2011b). Relationships between beta-amyloid and functional connectivity in different components of the default mode network in aging. Cerebral Cortex, 21, 2399–2407.PubMedCentralPubMedGoogle Scholar
  85. Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., et al. (2010). APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of Neurology, 67, 122–131.PubMedCentralPubMedGoogle Scholar
  86. Morrison, J. H., & Hof, P. R. (1997). Life and death of neurons in the aging brain. Science, 278, 412–419.PubMedGoogle Scholar
  87. Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., et al. (2012). Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. Journal of Neuropathology and Experimental Neurology, 71, 362–381.PubMedCentralPubMedGoogle Scholar
  88. Oh, H., Habeck, C., Madison, C., & Jagust, W. (2014). Covarying alterations in Abeta deposition, glucose metabolism, and gray matter volume in cognitively normal elderly. Human Brain Mapping, 35, 297–308.PubMedGoogle Scholar
  89. Park, D. C., & Reuter-Lorenz, P. (2009). The adaptive brain: aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173–196.PubMedCentralPubMedGoogle Scholar
  90. Pike, K. E., Ellis, K. A., Villemagne, V. L., Good, N., Chetelat, G., Ames, D., et al. (2011). Cognition and beta-amyloid in preclinical Alzheimer's disease: data from the AIBL study. Neuropsychologia, 49, 2384–2390.PubMedGoogle Scholar
  91. Raichle, M. E., & Snyder, A. Z. (2007). A default mode of brain function: a brief history of an evolving idea. NeuroImage, 37, 1083–1090. discussion 1097–9.PubMedGoogle Scholar
  92. Raz, N., Gunning-Dixon, F., Head, D., Rodrigue, K. M., Williamson, A., & Acker, J. D. (2004). Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume. Neurobiology of Aging, 25, 377–396.PubMedGoogle Scholar
  93. Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., et al. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proceedings of the National Academy of Sciences of the United States of America, 101, 284–289.PubMedCentralPubMedGoogle Scholar
  94. Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., et al. (2009). Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 106, 6820–6825.PubMedCentralPubMedGoogle Scholar
  95. Rentz, D. M., Amariglio, R. E., Becker, J. A., Frey, M., Olson, L. E., Frishe, K., et al. (2011). Face-name associative memory performance is related to amyloid burden in normal elderly. Neuropsychologia, 49, 2776–2783.PubMedCentralPubMedGoogle Scholar
  96. Rentz, D. M., Locascio, J. J., Becker, J. A., Moran, E. K., Eng, E., Buckner, R. L., et al. (2010). Cognition, reserve, and amyloid deposition in normal aging. Annals of Neurology, 67, 353–364.PubMedCentralPubMedGoogle Scholar
  97. Resnick, S. M., Sojkova, J., Zhou, Y., An, Y., Ye, W., Holt, D. P., et al. (2010). Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology, 74, 807–815.PubMedCentralPubMedGoogle Scholar
  98. Rodrigue, K. M., Kennedy, K. M., Devous, M. D., Sr., Rieck, J. R., Hebrank, A. C., Diaz-Arrastia, R., et al. (2012). beta-Amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology, 78, 387–395.PubMedCentralPubMedGoogle Scholar
  99. Roe, C. M., Fagan, A. M., Grant, E. A., Hassenstab, J., Moulder, K. L., Maue Dreyfus, D., et al. (2013). Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology, 80, 1784–1791.PubMedCentralPubMedGoogle Scholar
  100. Rosen, A. C., Prull, M. W., O'Hara, R., Race, E. A., Desmond, J. E., Glover, G. H., et al. (2002). Variable effects of aging on frontal lobe contributions to memory. Neuroreport, 13, 2425–2428.PubMedGoogle Scholar
  101. Rowe, C. C., Bourgeat, P., Ellis, K. A., Brown, B., Lim, Y. Y., Mulligan, R., et al. (2013). Predicting Alzheimer disease with beta-amyloid imaging: results from the Australian imaging, biomarkers, and lifestyle study of ageing. Annals of Neurology, 74, 905–913.PubMedGoogle Scholar
  102. Rowe, C. C., Ellis, K. A., Rimajova, M., Bourgeat, P., Pike, K. E., Jones, G., et al. (2010). Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiology of Aging, 31, 1275–1283.PubMedGoogle Scholar
  103. Savva, G. M., Wharton, S. B., Ince, P. G., Forster, G., Matthews, F. E., & Brayne, C. (2009). Age, neuropathology, and dementia. New England Journal of Medicine, 360, 2302–2309.PubMedGoogle Scholar
  104. Schott, J. M., Bartlett, J. W., Fox, N. C., & Barnes, J. (2010). Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Abeta1-42. Annals of Neurology, 68, 825–834.PubMedGoogle Scholar
  105. Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007). Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. Journal of Neuroscience, 27, 2866–2875.PubMedGoogle Scholar
  106. Shaw, P., Lerch, J. P., Pruessner, J. C., Taylor, K. N., Rose, A. B., Greenstein, D., et al. (2007). Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurology, 6, 494–500.Google Scholar
  107. Sheline, Y. I., Morris, J. C., Snyder, A. Z., Price, J. L., Yan, Z., D'Angelo, G., et al. (2010a). APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. Journal of Neuroscience, 30, 17035–17040.PubMedCentralPubMedGoogle Scholar
  108. Sheline, Y. I., Raichle, M. E., Snyder, A. Z., Morris, J. C., Head, D., Wang, S., et al. (2010b). Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biological Psychiatry, 67, 584–587.PubMedCentralPubMedGoogle Scholar
  109. Small, B. J., Fratiglioni, L., Viitanen, M., Winblad, B., & Backman, L. (2000). The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample. Archives of Neurology, 57, 839–844.PubMedGoogle Scholar
  110. Snitz, B. E., Weissfeld, L. A., Lopez, O. L., Kuller, L. H., Saxton, J., Singhabahu, D. M., et al. (2013). Cognitive trajectories associated with beta-amyloid deposition in the oldest-old without dementia. Neurology, 80, 1378–1384.PubMedCentralPubMedGoogle Scholar
  111. Sowell, E. R., Peterson, B. S., Thompson, P. M., Welcome, S. E., Henkenius, A. L., & Toga, A. W. (2003). Mapping cortical change across the human life span. Nature Neuroscience, 6, 309–315.PubMedGoogle Scholar
  112. Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., et al. (2011). Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging and the Alzheimer's association workgroup. Alzheimers Dement, 7, 280–292.PubMedCentralPubMedGoogle Scholar
  113. Sperling, R. A., Laviolette, P. S., O'Keefe, K., O'Brien, J., Rentz, D. M., Pihlajamaki, M., et al. (2009). Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron, 63, 178–188.PubMedCentralPubMedGoogle Scholar
  114. Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurology, 11, 1006–1012.PubMedCentralGoogle Scholar
  115. Stern, Y., Gurland, B., Tatemichi, T. K., Tang, M. X., Wilder, D., & Mayeux, R. (1994). Influence of education and occupation on the incidence of Alzheimer's disease. JAMA, 271, 1004–1010.PubMedGoogle Scholar
  116. Storandt, M., Mintun, M. A., Head, D., & Morris, J. C. (2009). Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition. Archives of Neurology, 66, 1476–1481.PubMedCentralPubMedGoogle Scholar
  117. Teri, L., McCurry, S. M., Edland, S. D., Kukull, W. A., & Larson, E. B. (1995). Cognitive decline in Alzheimer's disease: a longitudinal investigation of risk factors for accelerated decline. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 50A, M49–M55.Google Scholar
  118. Tosun, D., Schuff, N., Shaw, L. M., Trojanowski, J. Q., & Weiner, M. W. (2011). Relationship between CSF biomarkers of Alzheimer's disease and rates of regional cortical thinning in ADNI data. Journal of Alzheimer's Disease, 26(Suppl 3), 77–90.PubMedGoogle Scholar
  119. Vandenberghe, R., Van Laere, K., Ivanoiu, A., Salmon, E., Bastin, C., Triau, E., et al. (2010). 18 F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Annals of Neurology, 68, 319–329.PubMedGoogle Scholar
  120. Vannini, P., Hedden, T., Becker, J.A., Sullivan, C., Putcha, D., Rentz, D., et al. (2012). Age and amyloid-related alterations in default network habituation to stimulus repetition. Neurobiol Aging.Google Scholar
  121. Vannini, P., Hedden, T., Huijbers, W., Ward, A., Johnson, K. A., & Sperling, R. A. (2013). The ups and downs of the posteromedial cortex: age- and amyloid-related functional alterations of the encoding/retrieval flip in cognitively normal older adults. Cerebral Cortex, 23, 1317–1328.PubMedCentralPubMedGoogle Scholar
  122. Vemuri, P., Lesnick, T. G., Przybelski, S. A., Knopman, D. S., Roberts, R. O., Lowe, V. J., et al. (2012). Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Annals of Neurology, 72, 730–738.PubMedCentralPubMedGoogle Scholar
  123. Verghese, J., Lipton, R. B., Katz, M. J., Hall, C. B., Derby, C. A., Kuslansky, G., et al. (2003). Leisure activities and the risk of dementia in the elderly. New England Journal of Medicine, 348, 2508–2516.PubMedGoogle Scholar
  124. Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., et al. (2013). Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurology, 12, 357–367.Google Scholar
  125. Villemagne, V. L., Pike, K. E., Chetelat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., et al. (2011). Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Annals of Neurology, 69, 181–192.PubMedCentralPubMedGoogle Scholar
  126. Vos, S. J., Xiong, C., Visser, P. J., Jasielec, M. S., Hassenstab, J., Grant, E. A., et al. (2013). Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurology, 12, 957–965.Google Scholar
  127. Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., et al. (2002). Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 416, 535–539.PubMedGoogle Scholar
  128. Walsh, D. M., & Selkoe, D. J. (2007). A beta oligomers - a decade of discovery. Journal of Neurochemistry, 101, 1172–1184.PubMedGoogle Scholar
  129. Whitwell, J. L., Jack, C. R., Jr., Parisi, J. E., Senjem, M. L., Knopman, D. S., Boeve, B. F., et al. (2010). Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration? Neurology, 75, 2212–2220.PubMedCentralPubMedGoogle Scholar
  130. Whitwell, J. L., Josephs, K. A., Murray, M. E., Kantarci, K., Przybelski, S. A., Weigand, S. D., et al. (2008). MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study. Neurology, 71, 743–749.PubMedCentralPubMedGoogle Scholar
  131. Whitwell, J. L., Tosakulwong, N., Weigand, S. D., Senjem, M. L., Lowe, V. J., Gunter, J. L., et al. (2013). Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects? Neuroimage Clinical, 2, 249–257.PubMedCentralPubMedGoogle Scholar
  132. Wilson, R. S., Boyle, P. A., Yu, L., Barnes, L. L., Schneider, J. A., & Bennett, D. A. (2013a). Life-span cognitive activity, neuropathologic burden, and cognitive aging. Neurology, 81, 314–321.PubMedCentralPubMedGoogle Scholar
  133. Wilson, R. S., Yu, L., Trojanowski, J. Q., Chen, E. Y., Boyle, P. A., Bennett, D. A., et al. (2013b). TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurology, 70, 1418–1424.PubMedGoogle Scholar
  134. Wirth, M., Haase, C.M., Villeneuve, S., Vogel, J., Jagust, W.J. (2014). Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults. Neurobiol Aging.Google Scholar
  135. Wirth, M., Madison, C. M., Rabinovici, G. D., Oh, H., Landau, S. M., & Jagust, W. J. (2013a). Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not beta-amyloid in cognitively normal older individuals. Journal of Neuroscience, 33, 5553–5563.PubMedCentralPubMedGoogle Scholar
  136. Wirth, M., Oh, H., Mormino, E. C., Markley, C., Landau, S. M., & Jagust, W. J. (2013b). The effect of amyloid beta on cognitive decline is modulated by neural integrity in cognitively normal elderly. Alzheimers Dement, 9, 687–698 e1.Google Scholar
  137. Wirth, M., Villeneuve, S., Haase, C. M., Madison, C. M., Oh, H., Landau, S. M., et al. (2013c). Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurology, 70, 1512–1519.PubMedGoogle Scholar
  138. Wolf, A. B., Valla, J., Bu, G., Kim, J., Ladu, M. J., Reiman, E. M., et al. (2013). Apolipoprotein E as a beta-amyloid-independent factor in alzheimer's disease. Alzheimer's Research & Therapy, 5, 38.Google Scholar
  139. Wong, D. F., Rosenberg, P. B., Zhou, Y., Kumar, A., Raymont, V., Ravert, H. T., et al. (2010). In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18 F-AV-45 (florbetapir [corrected] F 18). Journal of Nuclear Medicine, 51, 913–920.PubMedCentralPubMedGoogle Scholar
  140. Zhang, M. Y., Katzman, R., Salmon, D., Jin, H., Cai, G. J., Wang, Z. Y., et al. (1990). The prevalence of dementia and Alzheimer's disease in Shanghai, China: impact of age, gender, and education. Annals of Neurology, 27, 428–437.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Neurology, Massachusetts General Hospital, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  2. 2.Martinos Center for Biomedical ImagingCharlestownUSA

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