Heterogeneity in Alzheimer’s Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials
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The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including the amount and distribution of AB deposition and spread of neurofibrillary tangles in different brain regions resulting in atypical clinical patterns and the existence of distinct AD variants. Heterogeneity in AD may be related to demographic factors (such as age, sex, educational and socioeconomic level) and genetic factors, which influence underlying pathology, the cognitive and behavioral phenotype, rate of progression, the occurrence of neuropsychiatric features, and the presence of comorbidities (e.g., vascular disease, neuroinflammation). Heterogeneity is also manifest in the individual resilience to the development of neuropathology (brain reserve) and the ability to compensate for its cognitive and functional impact (cognitive and functional reserve). The variability in specific cognitive profiles and types of functional impairment may be associated with different progression rates, and standard measures assessing progression may not be equivalent for individual cognitive and functional profiles. Other factors, which may govern the presence, rate, and type of progression of AD, include the individuals' general medical health, the presence of specific systemic conditions, and lifestyle factors, including physical exercise, cognitive and social stimulation, amount of leisure activities, environmental stressors, such as toxins and pollution, and the effects of medications used to treat medical and behavioral conditions. These factors that affect progression are important to consider while designing a clinical trial to ensure, as far as possible, well-balanced treatment and control groups.
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Differences in age at onset, rate of cognitive decline, and treatment responsiveness result from a combination of intrinsic factors such as genetic background, sex, and immune system variability, as well as extrinsic influences including dietary patterns, comorbid conditions, and environmental exposures.
“These differences result from a combination of intrinsic factors, such as genetic background, sex, and immune system variability, as well as extrinsic influences including dietary patterns, comorbid conditions, and environmental exposures418,419.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [418]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIncreasing research recognizes etiological and clinical heterogeneity of AD as a hallmark of AD and related diseases (ADRDs), making diagnosis, treatment, and drug development/testing more difficult.
“More and more research is recognizing the etiological and clinical heterogeneity of AD as a hallmark of AD and related diseases (ADRDs), which makes it more difficult to diagnose, treat, and develop and test new medications for AD.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [190]
Cognitive, neurological, psychological, and functional deficits in AD are complicated and different due to interactions with environmental factors.
“Cognitive, neurological, psychological, and functional deficits are complicated and different as a result of these interactions with environmental factors.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [190]
The interplay between phenotypes and genotypes is part of the heterogeneity of AD.
“The interplay between phenotypes and genotypes is part of the heterogeneity of AD.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [190]
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McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · cited 1× · see citing works
“In contrast to older trials, which used McKhann criteria [157] for AD dementia, more recent trials have required a clinical diagnosis of MCI or mild dementia due to AD, consistent with the NIA-AA Working Group Criteria [158, 159].”
ResultMild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864 · see citing works
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
The Cardiovascular Health Study: design and rationale.
Fried, L. P., Borhani, N. O., Enright, P., Furberg, C. D., Gardin, J. M., Kronmal, R. A., Kuller, L. H., Manolio, T. A., Mittelmark, M. B., Newman, A., et al. (1991) · Annals of Epidemiology · doi:10.1016/1047-2797(91)90005-w · Cited by 3,652 · see citing works
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565 · see citing works
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Alzheimer disease in the United States (2010–2050) estimated using the 2010 census
Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013) · Neurology · doi:10.1212/wnl.0b013e31828726f5 · Cited by 2,642 · see citing works
2020 Alzheimer's disease facts and figures
(2020) · Alzheimer's & Dementia · doi:10.1002/alz.12068 · Cited by 2,353 · see citing works
Cohort Profile: the Health and Retirement Study (HRS)
Sonnega, A., Faul, J. D., Ofstedal, M. B., Langa, K. M., Phillips, J. W., & Weir, D. R. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyu067 · Cited by 2,318 · see citing works
Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007) · Neurology · doi:10.1212/01.wnl.0000271090.28148.24 · Cited by 1,992 · see citing works
Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment
Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., Galasko, D., Jin, S., Kaye, J., Levey, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050151 · Cited by 1,844 · see citing works
Donanemab in Early Alzheimer’s Disease
Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100708 · Cited by 1,728 · cited 2× · see citing works
“Equivalent severity of brain pathology often presents with different severities of clinical symptoms and rates of progression [208, 212].”
BackgroundMethodSteen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703 · see citing works
Mild cognitive impairment: a concept in evolution
Petersen, R. C., Caracciolo, B., Brayne, C., Gauthier, S., Jelic, V., & Fratiglioni, L. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12190 · Cited by 1,694 · see citing works
Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis
Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., Aalten, P., Aarsland, D., Alcolea, D., et al. (2015) · JAMA · doi:10.1001/jama.2015.4668 · Cited by 1,610 · see citing works
The personal and clinical utility of polygenic risk scores
Torkamani, A., Wineinger, N. E., & Topol, E. J. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0018-x · Cited by 1,605 · see citing works
Neuropathology of older persons without cognitive impairment from two community-based studies
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006) · Neurology · doi:10.1212/01.wnl.0000219668.47116.e6 · Cited by 1,336 · see citing works
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · cited 1× · see citing works
“APOE is synthesized predominantly by astrocytes [20], and APOE e4 allele carriers show an increased density of Aβ deposition within the brain, reduced capacity to clear Aβ, and enhanced neuroinflammation [21].”
BackgroundBeach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103 · see citing works
Murray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., & Dickson, D. W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70156-9 · Cited by 972 · see citing works
Self-citationRates of hippocampal atrophy correlate with change in clinical status in aging and AD
Jack, C. R., Petersen, R. C., Xu, Y., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Tangalos, E. G., & Kokmen, E. (2000) · Neurology · doi:10.1212/wnl.55.4.484 · Cited by 937 · see citing works
Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., Cosio, D. M. O., Farrell, M., Quiroz, Y. T., Mormino, E. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1424 · Cited by 865 · see citing works
Ismail, Z., Smith, E. E., Geda, Y., Sultzer, D., Brodaty, H., Smith, G., Agüera‐Ortiz, L., Sweet, R., Miller, D., Lyketsos, C. G., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.017 · Cited by 818 · see citing works
The A4 Study: Stopping AD Before Symptoms Begin?
Sperling, R. A., Rentz, D. M., Johnson, K. A., Karlawish, J. H., Donohue, M., Salmon, D. P., & Aisen, P. S. S. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007941 · Cited by 756 · see citing works
Robinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., Suh, E., Bredenberg, C., Caswell, C., Van Deerlin, V. M., Yan, N., Yousef, A., et al. (2018) · Brain · doi:10.1093/brain/awy146 · Cited by 729 · see citing works
Barker, W., Luis, C. A., Kashuba, A., Luis, M., Harwood, D. G., Loewenstein, D., Waters, C., Jimison, P., Shepherd, E., Sevush, S., et al. (2002) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200210000-00001 · Cited by 706 · see citing works
Self-citationBuchhave, P. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.155 · Cited by 664 · see citing works
Salloway, S., Chalkias, S., Barkhof, F., Burkett, P., Barakos, J., Purcell, D., Suhy, J., Forrestal, F., Tian, Y., Umans, K., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2021.4161 · Cited by 619 · see citing works
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
Young, A. L., Marinescu, R. V., Oxtoby, N. P., Bocchetta, M., Yong, K., Firth, N. C., Cash, D. M., Thomas, D. L., Dick, K. M., Cardoso, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05892-0 · Cited by 596 · see citing works
Self-citationLate-Life Social Activity and Cognitive Decline in Old Age
James, B. D., Wilson, R. S., Barnes, L. L., & Bennett, D. A. (2011) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617711000531 · Cited by 590 · see citing works
Social resources and cognitive decline in a population of older African Americans and whites
Barnes, L. L., Mendes de Leon, C. F., Wilson, R. S., Bienias, J. L., & Evans, D. A. (2004) · Neurology · doi:10.1212/01.wnl.0000147473.04043.b3 · Cited by 572 · see citing works
Ossenkoppele, R., Pijnenburg, Y. A. L., Perry, D. C., Cohn-Sheehy, B. I., Scheltens, N. M. E., Vogel, J. W., Kramer, J. H., van der Vlies, A. E., Joie, R. L., Rosen, H. J., et al. (2015) · Brain · doi:10.1093/brain/awv191 · Cited by 548 · see citing works
Randomized trial of verubecestat for prodromal Alzheimer's disease
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., Tariot, P. N., Vellas, B., van Dyck, C. H., Boada, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812840 · Cited by 545 · see citing works
Microbes and Alzheimer’s Disease
Itzhaki, R. F., Lathe, R., Balin, B. J., Ball, M. J., Bearer, E. L., Braak, H., Bullido, M. J., Carter, C., Clerici, M., Cosby, S. L., et al. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160152 · Cited by 532 · see citing works
Ismail, Z., for the NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART), Agüera-Ortiz, L., Brodaty, H., Cieslak, A., Cummings, J., Fischer, C. E., Gauthier, S., Geda, Y. E., Herrmann, N., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-160979 · Cited by 530 · see citing works
Sperling, R., Salloway, S., Brooks, D. J., Tampieri, D., Barakos, J., Fox, N. C., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70015-7 · Cited by 512 · see citing works
Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis
Ryman, D. C., Acosta-Baena, N., Aisen, P. S., Bird, T., Danek, A., Fox, N. C., Goate, A., Frommelt, P., Ghetti, B., Langbaum, J. B. S., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000596 · Cited by 502 · see citing works
Gender and incidence of dementia in the Framingham Heart Study from mid‐adult life
Chêne, G., Beiser, A., Au, R., Preis, S. R., Wolf, P. A., Dufouil, C., & Seshadri, S. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.10.005 · Cited by 499 · see citing works
Depression and Social Identity: An Integrative Review
Cruwys, T., Haslam, S. A., Dingle, G. A., Haslam, C., & Jetten, J. (2014) · Personality and Social Psychology Review · doi:10.1177/1088868314523839 · Cited by 498 · see citing works
Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease
Janelidze, S., Teunissen, C. E., Zetterberg, H., Allué, J. A., Sarasa, L., Eichenlaub, U., Bittner, T., Ovod, V., Verberk, I. M. W., Toba, K., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.3180 · Cited by 494 · see citing works
Seshadri, S., Wolf, P. A., Beiser, A., Au, R., McNulty, K., White, R., & D'Agostino, R. B. (1997) · Neurology · doi:10.1212/wnl.49.6.1498 · Cited by 489 · see citing works
Lifecourse Social Conditions and Racial and Ethnic Patterns of Cognitive Aging
Glymour, M. M., & Manly, J. J. (2008) · Neuropsychology Review · doi:10.1007/s11065-008-9064-z · Cited by 481 · see citing works
Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People
De Meyer, G. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.179 · Cited by 462 · see citing works
Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.08.005 · Cited by 454 · see citing works
Resting‐state network dysfunction in Alzheimer's disease: A systematic review and meta‐analysis
Badhwar, A., Tam, A., Dansereau, C. L., Orban, P., Hoffstaedter, F., & Bellec, P. (2017) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2017.03.007 · Cited by 441 · see citing works
Sex differences in cognitive decline among US adults
Levine, D. A., Gross, A. L., Briceño, E. M., Tilton, N., Giordani, B. J., Sussman, J. B., Hayward, R. A., Burke, J. F., Hingtgen, S., Elkind, M. S. V., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.0169 · Cited by 440 · cited 3× · see citing works
“AD between men and women have also been attributed to social, health, and biological factors such as sex hormones [106].”
InfluentialSystematic review of dementia prevalence and incidence in United States race/ethnic populations
Mehta, K. M., & Yeo, G. W. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.06.2360 · Cited by 439 · see citing works
Reitz, C., Jun, G., Naj, A., Rajbhandary, R., Vardarajan, B. N., Wang, L.-S., Valladares, O., Lin, C.-F., Larson, E. B., Graff-Radford, N. R., et al. (2013) · JAMA · doi:10.1001/jama.2013.2973 · Cited by 431 · see citing works
Haan, M. N., Mungas, D. M., Gonzalez, H. M., Ortiz, T. A., Acharya, A., & Jagust, W. J. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2003.51054.x · Cited by 420 · see citing works
Neuroimaging correlates of pathologically-defined atypical Alzheimer’s disease
Whitwell, J. L., Dickson, D., Murray, M., Weigand, S., Tosakulwong, N., Senjem, M., Knopman, D., Boeve, B., Parisi, J., Petersen, R., et al. (2012) · Lancet Neurology · doi:10.1016/s1474-4422(12)70200-4 · Cited by 419 · see citing works
Rates of dementia in three ethnoracial groups
Gurland, B. J., Wilder, D. E., Lantigua, R., Stern, Y., Chen, J., Killeffer, E. H. P., & Mayeux, R. P. (1999) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(199906)14:6 · Cited by 417 · see citing works
Diversity and Disparity in Dementia: The Impact of Ethnoracial Differences in Alzheimer Disease
Chin, A. L., Negash, S., & Hamilton, R. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318211c6c9 · Cited by 416 · see citing works
Peters, M. E., Schwartz, S., Han, D., Rabins, P. V., Steinberg, M., Tschanz, J. T., & Lyketsos, C. G. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14040480 · Cited by 400 · see citing works
Desikan, R. S., Fan, C. C., Wang, Y., Schork, A. J., Cabral, H. J., Cupples, L. A., Thompson, W. K., Besser, L., Kukull, W. A., Holland, D., et al. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002258 · Cited by 395 · cited 1× · see citing works
“To identify genetic risk beyond that of APOE alone [72], several studies have assessed PRS with (APOE-PRS) versus without APOE (nonAPOE-PRS).”
BackgroundJanelidze, S., Berron, D., Smith, R. A., Strandberg, O. T., Proctor, N. K., Dage, J. L., Stomrud, E., Palmqvist, S., Mattsson, N., & Hansson, O. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4201 · Cited by 390 · see citing works
Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome
Lam, B., Masellis, M., Freedman, M., Stuss, D. T., & Black, S. E. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt155 · Cited by 386 · see citing works
Prevalence of mixed pathologies in the aging brain
Rahimi, J., & Kovács, G. G. (2014) · Alzheimer s Research & Therapy · doi:10.1186/s13195-014-0082-1 · Cited by 365 · see citing works
Yaffe, K., Falvey, C., Harris, T. B., Newman, A., Satterfield, S., Koster, A., Ayonayon, H., Simonsick, E., & Study, F. T. H. A. (2013) · BMJ · doi:10.1136/bmj.f7051 · Cited by 363 · see citing works
Weuve, J., Barnes, L. L., Mendes de Leon, C. F., Rajan, K. B., Beck, T., Aggarwal, N. T., Hebert, L. E., Bennett, D. A., Wilson, R. S., & Evans, D. A. (2018) · Epidemiology · doi:10.1097/ede.0000000000000747 · Cited by 340 · see citing works
How does brain insulin resistance develop in Alzheimer's disease?
De Felice, F. G., Lourenco, M. V., & Ferreira, S. T. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.12.004 · Cited by 337 · see citing works
Jack, C. R., Wiste, H. J., Weigand, S. D., Therneau, T. M., Knopman, D. S., Lowe, V., Vemuri, P., Mielke, M. M., Roberts, R. O., Machulda, M. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30077-7 · Cited by 333 · see citing works
Is the Risk of Developing Alzheimer's Disease Greater for Women than for Men?
Hebert, L. E., Scherr, P. A., McCann, J. J., Beckett, L. A., & Evans, D. A. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.2.132 · Cited by 331 · see citing works
Jack, C. R., Wiste, H. J., Therneau, T. M., Weigand, S. D., Knopman, D. S., Mielke, M. M., Lowe, V. J., Vemuri, P., Machulda, M. M., Schwarz, C. G., et al. (2019) · JAMA · doi:10.1001/jama.2019.7437 · Cited by 324 · see citing works
Vulnerable Neural Systems and the Borderland of Brain Aging and Neurodegeneration
Jagust, W. J. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.002 · Cited by 321 · see citing works
Attributable risk of Alzheimer's dementia attributed to age-related neuropathologies
Boyle, P. A., Yu, L., Leurgans, S. E., Wilson, R. S., Brookmeyer, R., Schneider, J. A., & Bennett, D. A. (2019) · Annals of Neurology · doi:10.1002/ana.25380 · Cited by 318 · see citing works
Type 2 diabetes mellitus and Alzheimer’s disease
Barbagallo, M. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i6.889 · Cited by 313 · see citing works
Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ɛ4 allele
van der Flier, W. M., Pijnenburg, Y. A. L., Fox, N. C., & Scheltens, P. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70306-9 · Cited by 306 · see citing works
Multiple pathologies are common and related to dementia in the oldest-old: The 90+ Study
Kawas, C. H., Kim, R. C., Sonnen, J. A., Bullain, S. S., Trieu, T., & Corrada, M. M. (2015) · Neurology · doi:10.1212/wnl.0000000000001831 · Cited by 303 · see citing works
Suspected non-Alzheimer disease pathophysiology — concept and controversy
Jack, C. R., Knopman, D. S., Chételat, G., Dickson, D. W., Fagan, A. M., Frisoni, G. B., Jagust, W. J., Mormino, E. C., Petersen, R. C., Sperling, R. A., et al. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.251 · Cited by 299 · see citing works
Bosco, D., Fava, A., Plastino, M., Montalcini, T., & Pujia, A. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01318.x · Cited by 283 · see citing works
Bourassa, K. J., Memel, M., Woolverton, C., & Sbarra, D. A. (2017) · Aging & Mental Health · doi:10.1080/13607863.2015.1081152 · Cited by 282 · see citing works
Reed, B. R., Mungas, D. M., Kramer, J. H., Ellis, W., Vinters, H. V., Zarow, C., Jagust, W. J., & Chui, H. C. (2007) · Brain · doi:10.1093/brain/awl385 · Cited by 282 · see citing works
Deelen, J., Beekman, M., Uh, H., Helmer, Q., Kuningas, M., Christiansen, L., Kremer, D., van der Breggen, R., Suchiman, H. E. D., Lakenberg, N., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00705.x · Cited by 280 · see citing works
The Motor Signature of Mild Cognitive Impairment: Results From the Gait and Brain Study
Montero‐Odasso, M., Oteng-Amoako, A., Speechley, M. R., Gopaul, K., Beauchet, O., Annweiler, C., & Hunter, S. W. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu155 · Cited by 275 · see citing works
Deelen, J., Beekman, M., Uh, H., Broer, L., Ayers, K. L., Tan, Q., Kamatani, Y., Bennet, A. M., Tamm, R., Trompet, S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu139 · Cited by 254 · see citing works
A Comprehensive Genetic Association Study of Alzheimer Disease in African Americans
Logue, M. W. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.646 · Cited by 250 · see citing works
Soininen, H., Solomon, A., Visser, P. J., Hendrix, S. B., Blennow, K., Kivipelto, M., Hartmann, T., Hallikainen, I., Hallikainen, M., Helisalmi, S., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30332-0 · Cited by 241 · see citing works
Infectious Agents and Neurodegeneration
Chiara, G. D., Marcocci, M. E., Sgarbanti, R., Civitelli, L., Ripoli, C., Piacentini, R., Garaci, E., Grassi, C., & Palamara, A. T. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8320-7 · Cited by 231 · see citing works
Dementia and Race: Are There Differences Between African Americans and Caucasians?
Miles, T. P., Froehlich, T. E., Bogardus, S. T., & Inouye, S. K. (2001) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2001.49096.x · Cited by 225 · see citing works
Cerebrospinal fluid -amyloid 1-42 concentration may predict cognitive decline in older women
Gustafson, D. R., Skoog, I., Rosengren, L., Zetterberg, H., & Blennow, K. (2006) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.100529 · Cited by 214 · see citing works
Potter, G. G., Plassman, B. L., Burke, J. R., Kabeto, M. U., Langa, K. M., Llewellyn, D. J., Rogers, M. A. M., & Steffens, D. C. (2009) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.04.1234 · Cited by 209 · see citing works
Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis
Huynh, T.-P. V., Liao, F., Francis, C. M., Robinson, G. O., Serrano, J. R., Jiang, H., Roh, J., Finn, M. B., Sullivan, P. M., Esparza, T. J., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.014 · Cited by 209 · see citing works
Prevalence and clinical phenotype of quadruple misfolded proteins in older adults
Karanth, S., Nelson, P. T., Katsumata, Y., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Cykowski, M. D., Jicha, G. A., Van Eldik, L. J., & Abner, E. L. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1741 · Cited by 206 · see citing works
Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β
Cohen, M. L., Kim, C., Haldiman, T., ElHag, M., Mehndiratta, P., Termsarasab, P., Lissemore, F. M., Shea, M., Cohen, Y., Chen, W., et al. (2015) · Brain · doi:10.1093/brain/awv006 · Cited by 202 · see citing works
Nebel, A., Kleindorp, R., Caliebe, A., Nothnagel, M., Blanché, H., Junge, O., Wittig, M., Ellinghaus, D., Flachsbart, F., Wichmann, H. ‐., et al. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.06.008 · Cited by 201 · see citing works
Emerging roles of pathogens in Alzheimer disease
Miklossy, J. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002006 · Cited by 199 · see citing works
Correia, S. C., Santos, R. X., Carvalho, C., Cardoso, S., Candeias, E., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2012) · Brain Research · doi:10.1016/j.brainres.2011.12.063 · Cited by 195 · see citing works
Microglial activation and tau burden predict cognitive decline in Alzheimer’s disease
Malpetti, M., Kievit, R. A., Passamonti, L., Jones, P. S., Tsvetanov, K. A., Rittman, T., Mak, E., Nicastro, N., Bevan-Jones, W. R., Su, L., et al. (2020) · Brain · doi:10.1093/brain/awaa088 · Cited by 194 · see citing works
Life Course Pathways to Racial Disparities in Cognitive Impairment among Older Americans
Zhang, Z., Hayward, M. D., & Yu, Y.-L. (2016) · Journal of Health and Social Behavior · doi:10.1177/0022146516645925 · Cited by 193 · see citing works
Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample
Brenowitz, W. D., Hubbard, R. A., Keene, C. D., Hawes, S. E., Longstreth, W. T., Woltjer, R. L., & Kukull, W. A. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.09.015 · Cited by 188 · see citing works
Naj, A. C., Jun, G., Reitz, C., Kunkle, B. W., Perry, W., Park, Y. S., Beecham, G. W., Rajbhandary, R. A., Hamilton-Nelson, K. L., Wang, L.-S., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.1491 · Cited by 185 · see citing works
Self-citationPolygenic score prediction captures nearly all common genetic risk for Alzheimer's disease
Escott-Price, V., Shoai, M., Pither, R., Williams, J., & Hardy, J. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.018 · Cited by 183 · see citing works
Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer’s disease
Grimm, A., Friedland, K., & Eckert, A. (2015) · Biogerontology · doi:10.1007/s10522-015-9618-4 · Cited by 182 · see citing works
Polygenic risk score analysis of pathologically confirmed Alzheimer disease
Escott‐Price, V., Myers, A., Huentelman, M. J., & Hardy, J. (2017) · Annals of Neurology · doi:10.1002/ana.24999 · Cited by 178 · see citing works
Alzheimer's pathology in primary progressive aphasia
Rohrer, J. D., Rossor, M. N., & Warren, J. D. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.020 · Cited by 175 · see citing works
Rabinovici, G. D. (2019) · Continuum · doi:10.1212/con.0000000000000700 · Cited by 170 · see citing works
Mild Behavioral Impairment and Subjective Cognitive Decline Predict Cognitive and Functional Decline
Ismail, Z., McGirr, A., Gill, S., Hu, S., Forkert, N. D., & Smith, E. E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201184 · Cited by 169 · see citing works
A multiomics approach to heterogeneity in Alzheimer’s disease: focused review and roadmap
Badhwar, A., McFall, G. P., Sapkota, S., Black, S. E., Chertkow, H. M., Duchesne, S., Masellis, M., Li, L., Dixon, R. A., & Bellec, P. (2019) · Brain · doi:10.1093/brain/awz384 · Cited by 168 · see citing works
Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
Risacher, S. L., Anderson, W. H., Charil, A., Castelluccio, P. F., Shcherbinin, S., Saykin, A. J., Schwarz, A. J., Initiative, F. T. A. D. N., Initiative, A. D. N., Weiner, M. W., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004670 · Cited by 163 · see citing works
Self-citationNon-Alzheimer’s contributions to dementia and cognitive resilience in The 90+ Study
Robinson, J. L., Corrada, M. M., Kovács, G. G., Dominique, M. A., Caswell, C., Xie, S. X., Lee, V. M. ‐., Kawas, C. H., & Trojanowski, J. Q. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1872-5 · Cited by 163 · see citing works
The role of APOE on lipid homeostasis and inflammation in normal brains
Rebeck, G. W. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075408 · Cited by 160 · see citing works
Biel, D., Brendel, M., Rubinski, A., Büerger, K., Janowitz, D., Dichgans, M., Franzmeier, N., & Initiative, A. D. N. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00880-x · Cited by 158 · see citing works
Condello, C., Lemmin, T., Stöhr, J., Nick, M., Wu, Y., Maxwell, A. M., Watts, J. C., Caro, C. D., Oehler, A., Keene, C. D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714966115 · Cited by 149 · see citing works
Incidence and prevalence of dementia in a multiethnic cohort of municipal retirees
Perkins, P. C., Annegers, J. F., Doody, R. S., Cooke, N., Aday, L. A., & Vernon, S. W. (1997) · Neurology · doi:10.1212/wnl.49.1.44 · Cited by 146 · see citing works
Siafarikas, N., Selbæk, G., Fladby, T., Benth, J. Š., Auning, E., & Aarsland, D. (2017) · International Psychogeriatrics · doi:10.1017/s1041610217001879 · Cited by 146 · see citing works
Garai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C. (2014) · Biochemistry · doi:10.1021/bi5008172 · Cited by 145 · see citing works
Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels
Babulal, G. M., Ghoshal, N., Head, D. M., Vernon, E. K., Holtzman, D. M., Benzinger, T. L. S., Fagan, A. M., Morris, J. C., & Roe, C. M. (2016) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2016.04.004 · Cited by 142 · see citing works
Cummings, J. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.05.006 · Cited by 140 · see citing works
Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease
El-Lebedy, D. H., Raslan, H. M., & Mohammed, A. M. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0329-1 · Cited by 139 · see citing works
Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia
Pink, A., Stokin, G. B., Bartley, M. M., Roberts, R. O., Sochor, O., Machulda, M. M., Krell‐Roesch, J., Knopman, D. S., Acosta, J. I., Christianson, T. J. H., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001307 · Cited by 138 · see citing works
Newman, A. B., Walter, S., Lunetta, K. L., Garcia, M. E., Slagboom, P. E., Christensen, K., Arnold, A. M., Aspelund, T., Aulchenko, Y. S., Benjamin, E. J., et al. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq028 · Cited by 138 · see citing works
An algorithmic approach to structural imaging in dementia
Harper, L., Barkhof, F., Scheltens, P., Schott, J. M., & Fox, N. C. (2014) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-306285 · Cited by 137 · see citing works
Holliday, E. G., Smith, A. V., Cornes, B. K., Buitendijk, G. H. S., Jensen, R. A., Sim, X., Aspelund, T., Aung, T., Baird, P. N., Boerwinkle, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053830 · Cited by 126 · see citing works
Sex and age interact to determine clinicopathologic differences in Alzheimer’s disease
Liesinger, A. M., Graff-Radford, N. R., Duara, R., Carter, R. E., Hanna Al-Shaikh, F. S., Koga, S., Hinkle, K. M., DiLello, S. K., Johnson, M. F., Aziz, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1908-x · Cited by 126 · see citing works
Self-citationHandbook of Assessment in Clinical Gerontology
Makover, R. B. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.10.1716 · Cited by 125 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · cited 1× · see citing works
“APOE has its greatest influence on the risk for AD between about 65 and 70 years of age and declines substantially by age 85 due to survival effects [11].”
BackgroundNonamnestic Presentations of Early-Onset Alzheimer’s Disease
Mendez, M., Lee, A. S., Joshi, A., & Shapira, J. (2012) · American Journal of Alzheimers Disease & Other Dementias · doi:10.1177/1533317512454711 · Cited by 117 · see citing works
Network localization of clinical, cognitive, and neuropsychiatric symptoms in Alzheimer’s disease
Tetreault, A. M., Phan, T. X., Orlando, D., Lyu, I., Kang, H., Landman, B. A., Darby, R. R., & Initiative, O. B. O. A. D. N. (2020) · Brain · doi:10.1093/brain/awaa058 · Cited by 115 · see citing works
González, H. M., Tarraf, W., Schneiderman, N., Fornage, M., Vásquez, P. M., Zeng, D., Youngblood, M., Gallo, L. C., Daviglus, M. L., Lipton, R. B., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.08.202 · Cited by 111 · see citing works
Hwang, J., Park, S. M., & Kim, S. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15102315 · Cited by 107 · see citing works
Sleegers, K., Bettens, K., De Roeck, A., Van Cauwenberghe, C., Cuyvers, E., Verheijen, J., Struyfs, H., Van Dongen, J., Vermeulen, S., Engelborghs, S., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.013 · Cited by 106 · see citing works
Besser, L. M., Teylan, M., & Nelson, P. T. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz126 · Cited by 104 · see citing works
Psychotic symptoms in Alzheimer disease: evidence for a distinct phenotype
Sweet, R. A., Nimgaonkar, V. L., Devlin, B., & Jeste, D. V. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001262 · Cited by 103 · see citing works
Relation of neuropathology with cognitive decline among older persons without dementia
Boyle, P. A., Yu, L., Wilson, R. S., Schneider, J. A., & Bennett, D. A. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00050 · Cited by 102 · see citing works
The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.010 · Cited by 102 · see citing works
Heterogeneity of Alzheimer’s disease: consequence for drug trials?
Devi, G., & Scheltens, P. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0455-y · Cited by 102 · see citing works
Rates of Decline in Alzheimer Disease Decrease with Age
Holland, D., Desikan, R. S., Dale, A. M., McEvoy, L. K., & Initiative, A. D. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042325 · Cited by 100 · see citing works
Zhou, Q., Zhao, F., Lv, Z., Zheng, C., Zheng, W., Sun, L., Wang, N., Pang, S., de Andrade, F. M., Fu, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087017 · Cited by 95 · see citing works
High Degree of Heterogeneity in Alzheimer's Disease Progression Patterns
Komarova, N. L., & Thalhauser, C. J. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002251 · Cited by 92 · see citing works
International, R., & Lines, L. (2014) · doi:10.3768/rtipress.2014.rr.0024.1412 · Cited by 89 · see citing works
Enfermedad de Alzheimer de inicio precoz y de inicio tardío: ¿son la misma entidad?
Tellechea, P., Pujol, N., Esteve‐Belloch, P., Echeveste, B., García-Eulate, M. R., Arbizu, J., & Riverol, M. (2015) · Neurología · doi:10.1016/j.nrl.2015.08.002 · Cited by 86 · see citing works
ApoE gene and exceptional longevity: Insights from three independent cohorts
Garatachea, N., Emanuele, E., Calero, M., Fuku, N., Arai, Y., Abe, Y., Murakami, H., Miyachi, M., Yvert, T., Verde, Z., et al. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.02.004 · Cited by 84 · see citing works
Qu, Y., Ma, Y., Huang, Y., Ou, Y., Shen, X., Chen, S.-D., Dong, Q., Tan, L., & Yu, J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.007 · Cited by 82 · see citing works
Early- and late-onset Alzheimer disease: Are they the same entity?
Tellechea, P., Pujol, N., Esteve‐Belloch, P., Echeveste, B., García-Eulate, M. R., Arbizu, J., & Riverol, M. (2017) · Neurología (English Edition) · doi:10.1016/j.nrleng.2015.08.009 · Cited by 81 · see citing works
Dietlin, S., Soto, M. E., Kiyasova, V., Pueyo, M. E., Mauléon, A. D., Delrieu, J., Ousset, P., & Vellas, B. J. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190025 · Cited by 80 · see citing works
Cohn‐Schwartz, E. (2020) · Innovation in Aging · doi:10.1093/geroni/igaa015 · Cited by 80 · see citing works
Samper-Ternent, R., Kuo, Y. F., Ray, L. A., Ottenbacher, K. J., Markides, K. S., & Al Snih, S. (2012) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2010.07.010 · Cited by 79 · see citing works
Finding Treatment Effects in Alzheimer Trials in the Face of Disease Progression Heterogeneity
Jutten, R. J., Sikkes, S. A. M., van der Flier, W. M., Scheltens, P., Visser, P. J., Tijms, B. M., & Initiative, A. D. N. (2021) · Neurology · doi:10.1212/wnl.0000000000012022 · Cited by 79 · see citing works
Older patients are still under-represented in clinical trials of Alzheimer's disease
Banzi, R., Camaioni, P., Tettamanti, M., Bertele’, V., & Lucca, U. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0201-2 · Cited by 74 · see citing works
Emanuel, J. E., López, O. L., Houck, P. R., Becker, J. T., Weamer, E. A., DeMichele‐Sweet, M. A. A., Kuller, L. H., & Sweet, R. A. (2010) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181e446c8 · Cited by 73 · see citing works
Herpes and Alzheimer’s Disease: Subversion in the Central Nervous System and How It Might Be Halted
Itzhaki, R. F. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160607 · Cited by 73 · see citing works
MRI-assessed atrophy subtypes in Alzheimer’s disease and the cognitive reserve hypothesis
Persson, K., Eldholm, R. S., Barca, M. L., Cavallin, L., Ferreira, D., Knapskog, A., Selbæk, G., Brækhus, A., Saltvedt, I. T., Westman, E., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186595 · Cited by 73 · see citing works
Ferreira, D., Pereira, J. B., Volpe, G., & Westman, E. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00524 · Cited by 73 · see citing works
Al-Shaikh, F. S. H., Duara, R., Crook, J., Lesser, E. R., Schaeverbeke, J., Hinkle, K., Ross, O., Ertekin-Taner, N., Pedraza, O., Dickson, D., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3606 · Cited by 73 · see citing works
Self-citationInfluence of Cognitive Reserve on Cognitive Trajectories
Li, X., Song, R., Qi, X., Xu, H., Yang, W., Kivipelto, M., Bennett, D. A., & Xu, W. (2021) · Neurology · doi:10.1212/wnl.0000000000012728 · Cited by 73 · see citing works
Age at onset and visuocognitive disturbances in Alzheimer disease.
Fujimori, M., Imamura, T., Yamashita, H., Hirono, N., Ikejiri, Y., Shimomura, T., & Mori, E. (1998) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199809000-00007 · Cited by 72 · see citing works
Yashin, A. I., Fang, F., Kovtun, M., Wu, D., Duan, M., Arbeev, K. G., Akushevich, I. V., Kulminski, A. M., Culminskaya, I. V., Zhbannikov, I. Y., et al. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.020 · Cited by 72 · see citing works
Hostage, C. A., Choudhury, K. R., Doraiswamy, P. M., Petrella, J. R., & Initiative, A. D. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054483 · Cited by 71 · see citing works
Qian, J., Betensky, R. A., Hyman, B. T., & Serrano-Pozo, A. (2021) · Neurology · doi:10.1212/wnl.0000000000011883 · Cited by 71 · see citing works
Enrichment and Stratification for Predementia Alzheimer Disease Clinical Trials
Holland, D., McEvoy, L. K., Desikan, R. S., Dale, A. M., & Initiative, A. D. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047739 · Cited by 70 · see citing works
Penninkilampi, R., Brothers, H. M., & Eslick, G. D. (2016) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-016-9722-5 · Cited by 69 · see citing works
Infection and Alzheimer's Disease: The APOE ε4 Connection and Lipid Metabolism
Urosevic, N., & Martins, R. N. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13407 · Cited by 68 · see citing works
Sex and gender in Alzheimer's disease – Does it matter?
Mielke, M. M., Ferretti, M. T., Iulita, M. F., Hayden, K., & Khachaturian, A. S. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.08.003 · Cited by 67 · see citing works
Apolipoprotein E, an important player in longevity and age-related diseases
Ang, L. S., Cruz, R. P., Hendel, A., & Granville, D. J. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.03.010 · Cited by 66 · see citing works
Sweet, R. A., Seltman, H. J., Emanuel, J. E., López, O. L., Becker, J. T., Bis, J. C., Weamer, E. A., DeMichele‐Sweet, M. A. A., & Kuller, L. H. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11121815 · Cited by 66 · see citing works
Roberto, N., Portella, M. J., Marquié, M., Alegret, M., Hernández, I., Mauleón, A., Rosende‐Roca, M., Ruiz, C. A., Antonio, E. E., Gil, S., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-83126-y · Cited by 66 · see citing works
Anderson, T. S., Ayanian, J. Z., Souza, J., & Landon, B. E. (2021) · JAMA · doi:10.1001/jama.2021.15286 · Cited by 66 · see citing works
Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population
Omoumi, A., Fok, A., Greenwood, T., Sadovnick, A. D., Feldman, H., & Hsiung, G. R. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.025 · Cited by 64 · see citing works
Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts
Resnick, S. M., Bilgel, M., Moghekar, A., An, Y., Cai, Q., Wang, M., Thambisetty, M., Prince, J. L., Zhou, Y., Soldan, A., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.001 · Cited by 64 · see citing works
Hashimoto, M., Yatabe, Y., Ishikawa, T., Fukuhara, R., Kaneda, K., Honda, K., Yuki, S., Ogawa, Y., Imamura, T., Kazui, H., et al. (2015) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000381800 · Cited by 63 · see citing works
Watson, M. A., Gay, L. J., Stebbings, W., Speakman, C., Bingham, S. A., & Loktionov, A. (2003) · Clinical Science · doi:10.1042/cs20020329 · Cited by 61 · see citing works
Xiao, Q., Liu, Z.-J., Tao, S., Sun, Y.-M., Jiang, D., Li, H., Chen, H., Liu, X., Lapin, B. R., Wang, C., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6271 · Cited by 61 · see citing works
Time, Sex, Gender, History, and Dementia
Rocca, W. A. (2017) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000187 · Cited by 61 · see citing works
The ApoE Gene Is Related with Exceptional Longevity: A Systematic Review and Meta-Analysis
Garatachea, N., Marin, P. J., Santos‐Lozano, A., Sanchis‐Gomar, F., Emanuele, E., & Lucía, A. (2014) · Rejuvenation Research · doi:10.1089/rej.2014.1605 · Cited by 59 · see citing works
The Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer’s Disease
Morgan, A. R., Touchard, S., O’Hagan, C., Sims, R., Majounie, E., Escott‐Price, V., Jones, L., Williams, J. H., & Morgan, B. P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160889 · Cited by 59 · see citing works
Alzheimer's disease gene signature says: beware of brain viral infections
Porcellini, E., Carbone, I., Ianni, M., & Licastro, F. (2010) · Immunity & Ageing · doi:10.1186/1742-4933-7-16 · Cited by 57 · see citing works
Aβ amyloid, cognition, and APOE genotype in healthy older adults
Lim, Y. Y., Ellis, K. A., Ames, D. J., Darby, D., Harrington, K., Martins, R. N., Masters, C. L., Rowe, C. C., Savage, G. R., Szoeke, C. E. I., et al. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.07.004 · Cited by 57 · see citing works
Shen, X., Li, J., Wang, H., Li, H., Huang, Y., Yang, Y., Tan, L., Dong, Q., Yu, J., & Initiative, A. D. N. (2020) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12104 · Cited by 57 · cited 1× · see citing works
“[198] conducted a cross-sectional and longitudinal analysis of data from 183 participants enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), divided into those who were cognitively normal (n = 97) and those with MCI (n = 86).”
Santos, O. A., Pedraza, O., Lucas, J. A., Duara, R., Greig‐Custo, M. T., Al‐Shaikh, F. S. H., Liesinger, A. M., Bieniek, K. F., Hinkle, K. M., Lesser, E. R., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.12.013 · Cited by 56 · see citing works
Self-citationLinks between Alzheimer's disease and diabetes
Sun, M., & Alkon, D. L. (2006) · Drugs of today · doi:10.1358/dot.2006.42.7.973588 · Cited by 54 · see citing works
Associations between apoE genotype and colon and rectal cancer
Slattery, M. L., Sweeney, C., Murtaugh, M. A., Ma, K.-N., Potter, J. D., Levin, T. R., Samowitz, W. S., & Wolff, R. K. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi088 · Cited by 53 · see citing works
Bekris, L. M., Galloway, N. M., Millard, S. P., Lockhart, D., Li, G., Galasko, D. R., Farlow, M. R., Clark, C. M., Quinn, J. F., Kaye, J. A., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.10.020 · Cited by 52 · see citing works
Initiative, A. D. N., Liu, Y., Tan, L., Wang, H.-F., Liu, Y., Hao, X., Tan, C., Jiang, T., Liu, B., Zhang, D., et al. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9388-7 · Cited by 51 · see citing works
Introduction to the Science of Recruitment and Retention Among Ethnically Diverse Populations
Dilworth‐Anderson, P. (2011) · The Gerontologist · doi:10.1093/geront/gnr043 · Cited by 51 · see citing works
Diabetes and the brain: issues and unmet needs
Bornstein, N. M., Brainin, M., Guekht, A. B., Skoog, I. G., & Korczyn, A. D. (2014) · Neurological Sciences · doi:10.1007/s10072-014-1797-2 · Cited by 49 · see citing works
Burke, S. L., Maramaldi, P., Cadet, T. J., & Kukull, W. A. (2016) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2016.04.006 · Cited by 49 · see citing works
Gao, L., Cui, Z., Shen, L., & Ji, H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150580 · Cited by 48 · see citing works
Burke, S. L., Hu, T., Naseh, M., Fava, N. M., O’Driscoll, J., Alvarez, D., Cottler, L. B., & Duara, R. (2018) · Aging Clinical and Experimental Research · doi:10.1007/s40520-018-1087-6 · Cited by 48 · see citing works
Self-citationDifferences in Alzheimer disease clinical trial outcomes based on age of the participants
Schneider, L. S., Kennedy, R., Wang, G., & Cutter, G. (2015) · Neurology · doi:10.1212/wnl.0000000000001376 · Cited by 43 · see citing works
Bridging the Gap Between Fluid Biomarkers for Alzheimer’s Disease, Model Systems, and Patients
Bjorkli, C., Sandvig, A., & Sandvig, I. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00272 · Cited by 41 · see citing works
Subgroups of Alzheimer's Disease: Stability of Empirical Clusters Over Time
Peter, J., Initiative, A. D. N., Abdulkadir, A., Kaller, C. P., Kümmerer, D., Hüll, M., Vach, W., & Klöppel, S. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140261 · Cited by 40 · see citing works
Molecular Linkages Between Diabetes and Alzheimer's Disease: Current Scenario and Future Prospects
Dar, T. A., SHEIKH, I. A., Ganie, S. A., Ali, R., Singh, L. R., Gan, S. H., Kamal, M. A., & Zargar, M. A. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113126660135 · Cited by 38 · see citing works
Goyal, D., Tjandra, D., Migrino, R. Q., Giordani, B., Syed, Z., Wiens, J., & Initiative, A. D. N. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.06.007 · Cited by 37 · see citing works
Lü, F., Guan, H., Gong, B., Liu, X., Zhu, R., Wang, Y., Qian, J., Zhou, T., Lan, X., Wang, P., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099580 · Cited by 36 · see citing works
Blanken, A. E., Jang, J. Y., Ho, J. K., Edmonds, E. C., Han, S. D., Bangen, K. J., & Nation, D. A. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.0413 · Cited by 36 · see citing works
Sun, Y., Xu, W., Chen, K., Shen, X., Tan, L., Yu, J., & Initiative, A. D. N. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01675-2 · Cited by 35 · see citing works
Ma, X., Yu, J., Wang, W., Wang, H.-F., Liu, Q., Zhang, W., & Tan, L. (2013) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8217-7 · Cited by 34 · see citing works
Reply: the early pathological process in sporadic Alzheimer’s disease
Braak, H., & Tredici, K. D. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1170-1 · Cited by 32 · see citing works
Suzuki, K., Hirakawa, A., Ihara, R., Iwata, A., Ishii, K., Ikeuchi, T., Sun, C., Donohue, M., Iwatsubo, T., & Alzheimer's Disease Neuroimaging Initiative, J. A. D. N. I. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12007 · Cited by 32 · see citing works
Association of GWAS Top Genes With Late-Onset Alzheimer’s Disease in Colombian Population
Moreno, D. J., Ruiz, S., Rios, A. M., Lopera, F., Ostos, H., Via, M., & Bedoya, G. (2017) · American Journal of Alzheimers Disease & Other Dementias · doi:10.1177/1533317516679303 · Cited by 30 · see citing works
Ye, B. S., Seo, S. W., Lee, Y., Kim, S. Y., Choi, S. H., Lee, Y. M., Kim, D. H., Han, H. J., Na, D. L., & Kim, E. (2012) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000342973 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Yashin AI, Fang F, Kovtun M, Wu D, Duan M, Arbeev K, et al. Hidden heterogeneity in Alzheimer's disease: insights from genetic associa- tion studies and other analyses. Exp Gerontol. 2018;107:148-60.
Cited by
Sorted by citations
Ren, F., Wei, J., Chen, Q., Hu, M., Yu, L., Mi, J., Zhou, X., Qin, D., Wu, J., & Wu, A. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.030 · Cited by 97 · see citing works
Nagori, K., Nakhate, K. T., Yadav, K., Ajazuddin, & Pradhan, M. (2023) · Future Pharmacology · doi:10.3390/futurepharmacol3040053 · Cited by 61 · see citing works
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · see citing works
“More work has to be conducted to take this variability into account in order to improve the results of AD clinical trials [190–192].”
BackgroundIdentification of metabolism-related subtypes and feature genes in Alzheimer’s disease
Lian, P., Cai, X., Wang, C., Liu, K., Yang, X., Wu, Y., Zhang, Z., Ma, Z., Cao, X., & Xu, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04324-y · Cited by 29 · see citing works
Natural Products from Plants and Algae for Treatment of Alzheimer’s Disease: A Review
Klose, J., Griehl, C., Roßner, S., & Schilling, S. (2022) · Biomolecules · doi:10.3390/biom12050694 · Cited by 23 · see citing works
A review of neuroimaging-based data-driven approach for Alzheimer’s disease heterogeneity analysis
Liu, L., Sun, S., Kang, W., Wu, S., & Lin, L. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2023-0033 · Cited by 16 · see citing works
Zhou, M., Tang, A. S., Zhang, H., Xu, Z., Ke, A. M. C., Su, C., Huang, Y., Mantyh, W. G., Jaffee, M. S., Rankin, K. P., et al. (2025) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2025.104820 · Cited by 9 · see citing works
Wei, H., Wu, C., Yuan, Y., & Lai, L. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1249682 · Cited by 3 · see citing works
Abrol, A., Calhoun, V. D., & Initiative, T. A. D. N. (2025) · Human Brain Mapping · doi:10.1002/hbm.70391 · Cited by 3 · see citing works
- Authors
- Duara, R., & Barker, W.
- Affiliations
- Florida International University (US)
- Mount Sinai Medical Center (US)
- Corresponding author
- Barker, Warren
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 19
- Issue
- 1
- Pages
- 8-25
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC9130395
- OpenAlex
- W4210391623
- Cited by
- 187
- References
- 215
- Citations by year
- 2026: 59 · 2025: 64 · 2024: 46 · 2023: 12 · 2022: 5
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (1P30AG066506-01)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, disease heterogeneity, disease progression rate, amyloid-beta deposition, neurofibrillary tangles, atypical presentation, brain reserve, cognitive reserve, functional reserve, neuropsychiatric symptoms, comorbidities, vascular disease, neuroinflammation, genetic factors, demographic factors, lifestyle factors, clinical trial design
- MeSH terms
- Alzheimer Disease, Brain, Humans, Disease Progression
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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