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

Neuropsychology Review

Volumn 24, Issue 3, 2014, Pages 300-312

  Mormino, Elizabeth C ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Aging; Amyloid PET imaging; Beta amyloid; Preclinical Alzheimer s disease; Resilience

Indexed keywords

AMYLOID BETA PROTEIN; BIOLOGICAL MARKER;

AGE; ALZHEIMER DISEASE; ATROPHY; BRAIN; COGNITION; FEMALE; HUMAN; MALE; MEMORY DISORDERS; METABOLISM; PATHOLOGY; PHYSIOLOGY; RISK FACTOR; SEX DIFFERENCE;

AGE FACTORS; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ATROPHY; BIOMARKERS; BRAIN; COGNITION; FEMALE; HUMANS; MALE; MEMORY DISORDERS; RISK FACTORS; SEX FACTORS;

EID: 84939888715     PISSN: 10407308     EISSN: 15736660     Source Type: Journal    
DOI: 10.1007/s11065-014-9267-4     Document Type: Review

References (140)

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.
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.
3. Alz.org. (2014). Alzheimer’s Disease Facts and Figures.
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.
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.
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.
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.
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.
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.
10. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18, 351–357.
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.
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.
13. Buckner, R. L., & Vincent, J. L. (2007). Unrest at rest: default activity and spontaneous network correlations. NeuroImage, 37, 1091–1096. discussion 1097–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
55. Jagust, W. (2013). Vulnerable neural systems and the borderland of brain aging and neurodegeneration. Neuron, 77, 219–234.
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.
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.
58. Jagust, W. J., & Mormino, E. C. (2011). Lifespan Brain Activity, β-Amyloid, and Alzheimer's Disease. Trends in Cognitive Science, 15, 520–526.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
74. Lott, I. T., Head, E., Doran, E., & Busciglio, J. (2006). Beta-amyloid, oxidative stress and down syndrome. Current Alzheimer Research, 3, 521–528.
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.
76. Mahley, R. W., & Huang, Y. (2012). Apolipoprotein e sets the stage: response to injury triggers neuropathology. Neuron, 76, 871–885.
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.
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.
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.
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.
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.
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.
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.
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.
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.
86. Morrison, J. H., & Hof, P. R. (1997). Life and death of neurons in the aging brain. Science, 278, 412–419.
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.
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.
89. Park, D. C., & Reuter-Lorenz, P. (2009). The adaptive brain: aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173–196.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
114. Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurology, 11, 1006–1012.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
128. Walsh, D. M., & Selkoe, D. J. (2007). A beta oligomers - a decade of discovery. Journal of Neurochemistry, 101, 1172–1184.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.