Attributable risk of Alzheimer's dementia attributed to age-related neuropathologies
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Objective: The degree to which Alzheimer's versus other neuropathologies contribute to the risk of Alzheimer's dementia is unknown. We examined the risk of Alzheimer's dementia attributable to pathologic AD and 8 other neuropathologies. Methods: Participants (n = 1,161) came from 2 clinical‐pathological studies of aging. Multivariable logistic regression models examined associations of 8 neuropathological indices with Alzheimer's dementia and quantified the percentage of cases attributable to each. Furthermore, because some dementia cases are not driven by common neuropathologies, we re‐estimated the attributable risks after empirically adjusting for such cases. Results: Of 1,161 persons, 512 (44.1%) had Alzheimer's dementia at time of death. With the exception of microinfarcts, all neuropathological indices were independently associated with greater odds of Alzheimer's dementia. Two hundred ten (41.0%) Alzheimer's dementia cases were attributable to pathological AD. Separately, 8.9% were attributable to macroscopic infarcts, 10.8% to Lewy bodies, 5.2% to hippocampal sclerosis, 11.7% to transactive response DNA‐binding protein 43, 8.1% to cerebral amyloid angiopathy, 6.0% to atherosclerosis, and 5.2% to arteriolosclerosis. A total of 83.3% of cases were attributable to all 8 indices combined. However, after further adjustment for cases driven by other factors, a total of 67.5% of cases were attributable to all 8 neuropathologic indices combined. Interpretation: Pathological AD accounts for a considerable percentage of Alzheimer's dementia cases, but multiple other neuropathologies also contribute. In total, just over two‐thirds of Alzheimer's dementia cases are attributable to common age‐related neuropathologies, suggesting that other disease and resilience factors are important. ANN NEUROL 2019;85:114–124.
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One RCT compared care at a specialist medical and mental health unit to usual care for 600 confused people older than 65 years, acutely admitted to hospital, and found no difference in the primary outcome of days spent at home or in hospital, but increased family satisfaction.
“One RCT compared care at a specialist medical and mental health unit to usual care for 600 confused people older than 65 years, acutely admitted to hospital and found no difference in the primary outcome of days spent at home or in hospital, but increased family satisfaction.292”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [292]
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Experimental — accuracy not yet measuredStudies suggest that mixed dementia is the norm, not just for those diagnosed with Alzheimer's dementia but also for those diagnosed with other types of dementia.
“Studies suggest that mixed dementia is the norm, not just for those diagnosed with Alzheimer's dementia but also for those diagnosed with other types of dementia.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [38]
The Introduction says Alzheimer’s dementia is most commonly the result of mixed neuropathologies, and the Discussion describes mixed neuropathology as the most common cause of dementia generally. The paper does not establish that mixed pathology is the norm specifically among people diagnosed with other types of dementia; its analyses focus on Alzheimer’s dementia. (LLM, conf=0.82)
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Frailty Trajectories Preceding Dementia in the US and UK
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When Alzheimer's is LATE : Why Does it Matter?
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Self-citationCognitive Impairment in Older Adults and Therapeutic Strategies
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Brain DNA Methylation Patterns in CLDN5 Associated With Cognitive Decline
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Vascular pathology and pathogenesis of cognitive impairment and dementia in older adults
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Self-citationBlood Pressure and Vascular Cognitive Impairment
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Contribution of Modifiable Midlife and Late-Life Vascular Risk Factors to Incident Dementia
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2026 Alzheimer's disease facts and figures
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- Authors
- Boyle, P. A., Yu, L., Leurgans, S. E., Wilson, R. S., Brookmeyer, R., Schneider, J. A., & Bennett, D. A.
- Affiliations
- Rush University Medical Center (US)
- University of California, Los Angeles (US)
- Corresponding author
- Boyle, Patricia A.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2018-12-19
- Volume
- 85
- Issue
- 1
- Pages
- 114-124
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC10128614
- OpenAlex
- W2901473819
- Cited by
- 318
- References
- 32
- Citations by year
- 2026: 36 · 2025: 69 · 2024: 41 · 2023: 37 · 2022: 43 · 2021: 42 · 2020: 32 · 2019: 18
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Illinois Department of Public Health
- National Institute on Aging (R01AG34374, R01AG42210, R01AG17917, P30AG10161, R01AG15819)
- 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 dementia, neuropathology, attributable risk, Lewy bodies, cerebral amyloid angiopathy, tau pathology, hippocampal sclerosis, atherosclerosis, arteriolosclerosis, microinfarcts, dementia risk factors
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Dementia, Female, Humans, Longitudinal Studies, Male, Risk Factors
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