A third of community-dwelling elderly with intermediate and high level of Alzheimer’s neuropathologic changes are not demented: A meta-analysis
Abstract
This systematic review and meta-analysis assessed the bidirectional association between AD pathology and dementia in community-dwelling elderly populations. We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and references of the pertinent articles for community/population-based longitudinal cohorts with regular assessment of cognitive status of participants followed by postmortem neuropathology data, with no language and date restrictions, until 20 September 2019. Finally, we retrieved 18 articles with data from 17 cohorts comprising 4677 persons. Dementia was twice as likely in participants with definitive neuropathological indicator for AD compared to those without it: moderate/high Braak and Braak (BB) stages III-VI of neurofibrillary tangles (54 % vs. 26 % in participants with BB stages 0-II), the Consortium to Establish a Registry for AD (CERAD) moderate/frequent neuritic plaques scores (64 % vs. 33 % in participants with CERAD none/infrequent), and National Institute on Aging and the Reagan Institute of the Alzheimer's Association criteria intermediate/high AD probability (52 % vs. 28 % in participants with no/low AD probability). Accordingly, a substantial proportion of community-dwelling elderly people with definitive AD pathology may not develop dementia. Brain reserve or contribution of other factors and pathologies, such as vascular and degenerative pathology to dementia might explain this apparent discrepancy. These findings also suggest caution in equating Alzheimer pathology biomarkers with dementia.
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In a meta-analysis involving 4677 individuals, one-third of those with intermediate-to-high AD neuropathology did not develop dementia during their lifetime.
“a meta‐analysis involving 4677 individuals reported that one‐third of those with intermediate‐to‐high AD neuropathology did not develop dementia during their lifetime.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [175]
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Avan, A., Amiri, A., Mokhber, N., Erfanian, M., Cipriano, L. E., Stranges, S., Shojaeianbabaei, G., Abootalebi, S., & Azarpazhooh, M. R. (2021) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2021.05.044 · Cited by 1 · see citing works
Self-citationAnti-Amyloid Agents: A Self-Fulfilling prophecy
Giannakis, A., & Konitsiotis, S. (2025) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2025.111338
Stable neuronal representations underlie cognitive resilience to Alzheimer's disease pathology
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Şimşekçi, U., & Cesaretli, Y. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1882211
Wang, X., Wang, Y., Pang, K., & Zheng, C. (2026) · eLife · doi:10.7554/elife.112274
Wang, X., Wang, Y., Pang, K., & Zheng, C. (2026) · eLife · doi:10.7554/elife.112274.1
- Authors
- Azarpazhooh, M. R., Avan, A., Cipriano, L. E., Munoz, D. G., Erfanian, M., Amiri, A., Stranges, S., & Hachinski, V.
- Affiliations
- Western University (CA)
- Mashhad University of Medical Sciences (IR)
- Ferdowsi University of Mashhad (IR)
- Corresponding author
- Hachinski, Vladimir
- ORCID
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 58
- Pages
- 101002
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2996885560
- Cited by
- 32
- References
- 63
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Munich-Centre for Advanced Photonics
- Orange County Community Foundation
- City, University of London
- Canadian Aeronautics and Space Institute
- Singapore-MIT Alliance for Research and Technology Centre
- ACT Government
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, Alzheimer's disease pathology, dementia, community-dwelling older adults, neurofibrillary tangles, Braak stages, neuritic plaques, CERAD, brain reserve, postmortem neuropathology, cognitive status
- MeSH terms
- Neuropathology, Aged, Alzheimer Disease, Brain, Dementia, Humans, Neurofibrillary Tangles, Independent Living, Plaque, Amyloid
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