Late-onset Alzheimer Disease
Open accessAbstract
PURPOSE OF REVIEW: Alzheimer disease (AD) is the most common cause of late-onset dementia. This article describes the epidemiology, genetic and environmental risk factors, clinical diagnosis, biomarkers, and treatment of late-onset AD, defined by age of onset of 65 years or older. RECENT FINDINGS: An estimated 5.7 million Americans are living with AD dementia, with the number of affected individuals growing rapidly because of an aging population. Vascular risk factors, sleep disorders, and traumatic brain injury are associated with an increased risk of AD, while increased cognitive and physical activity throughout the lifespan reduce the risk of disease. The primary genetic risk factor for late-onset AD is the apolipoprotein E (APOE) ε4 allele. AD typically presents with early and prominent episodic memory loss, although this clinical syndrome is neither sensitive nor specific for underlying AD neuropathology. Emerging CSF and imaging biomarkers can now detect the key neuropathologic features of the disease (amyloid plaques, neurofibrillary tangles, and neurodegeneration) in living people, allowing for characterization of patients based on biological measures. A comprehensive treatment plan for AD includes use of symptomatic medications, optimal treatment of comorbid conditions and neuropsychiatric symptoms, counseling about safety and future planning, and referrals to community resources. SUMMARY: AD is very common in older neurologic patients. Neurologists should set the standard for the diagnosis and care of patients with AD and should be familiar with emerging biomarkers that have transformed AD research and are primed to enter the clinical arena.
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Unlike FAD, SAD is a more complex disorder in terms of associated triggers, with environmental and genetic elements likely driving the pathology.
“Unlike FAD, SAD is a more complex disorder in terms of the associated triggers. The confluence of environmental and genetic elements is likely to drive the pathology [57].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [57]
The Genetic Risk Factors section (p. 3) describes late-onset AD as a complex genetic disorder, and Environmental Risk Factors (p. 3) identifies environmental factors associated with dementia risk. The paper does not establish that these factors jointly drive AD pathology; it says links between many environmental factors and the specific pathobiology of AD are less established. Its comparison with familial early-onset AD (Key Points, p. 4) does not explicitly characterize sporadic disease as more complex. (LLM, conf=0.86)
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Cites
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
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · 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
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 · see citing works
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · 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
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925 · see citing works
Self-citation2018 Alzheimer's disease facts and figures
Alzheimer's Association (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.001 · Cited by 1,912 · see citing works
Baumgart, M., Snyder, H. M., Carrillo, M. C., Fazio, S., Kim, H., & Johns, H. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.016 · Cited by 1,660 · see citing works
Knopman, D. S., DeKosky, S. T., Cummings, J. L., Chui, H., Corey–Bloom, J., Relkin, N., Small, G. W., Miller, B., & Stevens, J. C. (2001) · Neurology · doi:10.1212/wnl.56.9.1143 · Cited by 1,410 · see citing works
Yaffe, K., Laffan, A. M., Harrison, S. L., Redline, S., Spira, A. P., Ensrud, K. E., Ancoli-Israel, S., & Stone, K. L. (2011) · JAMA · doi:10.1001/jama.2011.1115 · Cited by 1,137 · see citing works
Inequalities in dementia incidence between six racial and ethnic groups over 14 years
Mayeda, E. R., Glymour, M. M., Quesenberry, C. P., & Whitmer, R. A. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.12.007 · Cited by 883 · see citing works
Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis
Neu, S. C., Pa, J., Kukull, W., Beekly, D., Kuzma, A., Gangadharan, P., Wang, L.-S., Romero, K., Arneric, S. P., Redolfi, A., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.2188 · Cited by 674 · see citing works
Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
Frisoni, G. B., Boccardi, M., Barkhof, F., Blennow, K., Cappa, S., Chiotis, K., Démonet, J.-F., Garibotto, V., Giannakopoulos, P., Gietl, A., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30159-x · Cited by 626 · see citing works
Antipsychotic Drug Use and Mortality in Older Adults with Dementia
Gill, S. S., Bronskill, S. E., Normand, S.-L. T., Anderson, G. M., Sykora, K., Lam, K., Bell, C. M., Lee, P. E., Fischer, H. D., Herrmann, N., et al. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-11-200706050-00006 · Cited by 624 · see citing works
Alzheimer's disease drug development pipeline: 2017
Cummings, J., Lee, G., Mortsdorf, T., Ritter, A., & Zhong, K. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.05.002 · Cited by 549 · see citing works
Perry, D. C., Sturm, V. E., Peterson, M. J., Pieper, C. F., Bullock, T., Boeve, B. F., Miller, B. L., Guskiewicz, K. M., Berger, M. S., Kramer, J. H., et al. (2016) · Journal of Neurosurgery · doi:10.3171/2015.2.jns14503 · Cited by 440 · 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 · see citing works
The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Carmona, S., Zahs, K., Wu, E., Dakin, K., Bras, J., & Guerreiro, R. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30232-1 · Cited by 244 · see citing works
Flagged first, then by citations
Research works printed but not linked: 12
- 1 Alzheimer A. Uber eine eigenaritage, schweren Erkrankung der Hirnrinde. Neurol Zbl 1907;25:1134.
- 3 Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2018;90(3):126 -135. doi:10.1212/WNL.0000000000004826. · DOI · Paper page
- 4 Hebert LE, Beckett LA, Scherr PA, Evans DA. Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis Assoc Disord 2001;15(4):169 -173.
- 7 Chêne G, Beiser A, Au R, et al. Gender and incidence of dementia in the Framingham Heart Study from mid-adult life. Alzheimers Dement 2015;11(3):310 -320. doi:10.1016/j.jalz.2013.10.005. · DOI · Paper page
- 8 Brodaty H, Seeher K, Gibson L. Dementia time to death: a systematic literature review on survival time and years of life lost in people with dementia. Int Psychogeriatr 2012;24(7):1034 -1045. doi:10.1017/S1041610211002924. · DOI · Paper page
- 10 Ritchie K, Ritchie CW, Yaffe K, et al. Is late-onset Alzheimer ' s disease really a disease of midlife? Alzheimers Dement (N Y) 2015;1(2):122 -130. doi:10.1016/j.trci.2015.06.004. · DOI
- 11 Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer ' s disease prevalence. Lancet Neurol 2011;10(9):819 -828. doi:10.1016/S1474-4422(11)70072-2. · DOI
- 12 Ju YE, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology -a bidirectional relationship. Nat Rev Neurol 2014;10(2):115 -119. doi:10.1038/nrneurol.2013.269. · DOI · Paper page
- 15 Ehrenberg AJ, Nguy AK, Theofilas P, et al. Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer ' s disease. Neuropathol Appl Neurobiol 2017;43(5):393 -408. doi:10.1111/nan.12387. · DOI
- 16 Carmona S, Hardy J, Guerreiro R. The genetic landscape of Alzheimer disease. Handb Clin Neurol 2018;148:395 -408. doi:10.1016/B978-0444-64076-5.00026-0. · DOI
- 17 Liu CC, Liu CC, Kanekiyo T, et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013;9(2):106 -118. doi:10.1038/nrneurol.2012.263. · DOI · Paper page
- 19 Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer ' s diseases. Neurobiol Dis 2014; 72(pt A):3 -12. doi:10.1016/j.nbd.2014.08.025. · DOI · Paper page
Cited by
Sorted by citations
Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies
Alkhalifa, A. E., Al-Ghraiybah, N. F., Odum, J., Shunnarah, J. G., Austin, N., & Kaddoumi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216288 · Cited by 212 · see citing works
Duara, R., & Barker, W. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01185-z · Cited by 187 · see citing works
Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00339 · Cited by 170 · see citing works
Regional associations of white matter hyperintensities and early cortical amyloid pathology
Lorenzini, L., Ansems, L. T., Lopes Alves, I., Ingala, S., Vállez García, D., Tomassen, J., Sudre, C., Salvadó, G., Shekari, M., Operto, G., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac150 · Cited by 36 · see citing works
Henao‐Restrepo, J., López‐Murillo, C., Valderrama‐Carmona, P., Orozco‐Santa, N., Gomez, J., Gutiérrez‐Vargas, J., Moraga, R., Toledo, J., Littau, J. L., Härtel, S., et al. (2023) · Brain Pathology · doi:10.1111/bpa.13119 · Cited by 11 · see citing works
- Authors
- Rabinovici, G. D.
- Corresponding author
- Rabinovici, Gil D.
- ORCID
- Rabinovici, Gil D.
- Venue
- Continuum
- Published
- 2019-02
- Volume
- 25
- Issue
- 1
- Pages
- 14-33
- ISSN
- 1080-2371 (ISSN-L)
- 1538-6899
- PMC
- PMC6548536
- OpenAlex
- W2912680348
- Cited by
- 170
- References
- 20
- Citations by year
- 2026: 27 · 2025: 32 · 2024: 25 · 2023: 23 · 2022: 37 · 2021: 10 · 2020: 15 · 2019: 1
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CONTINUUM Lifelong Learning in Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Eli Lilly and Company
- Eisai
- National Institutes of Health (AG019724, AG057195, AG032289)
- Avid Radiopharmaceuticals
- National Institute on Aging (R01AG045611, R01AG038791, R01AG032289, P50AG023501)
- 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
- late-onset Alzheimer's disease, dementia epidemiology, APOE ε4, vascular risk factors, sleep disorders, traumatic brain injury, cerebrospinal fluid biomarkers, amyloid plaques, neurofibrillary tangles, neurodegeneration, symptomatic treatment, neuropsychiatric symptoms, comorbidities, population aging
- MeSH terms
- Late Onset Disorders, Activities of Daily Living, Alzheimer Disease, Cognition, Humans, Memory Disorders, Cognitive Dysfunction
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