Sex Differences in the Clinical Manifestations of Alzheimer Disease Pathology
Abstract
Context Sex differences in risk of clinically diagnosed Alzheimer disease (AD) have been studied extensively, but little is known about the relation of the pathologic indices of AD to the clinical manifestations of the disease in men compared with women. Objective To test whether the relation of AD pathology to the clinical manifestations of the disease differs in men and women. Design Longitudinal, clinicopathologic cohort study. Participants and setting Analyses were conducted on 141 older Catholic clergy members who underwent detailed annual clinical evaluations and brain autopsy at death. The number of neuritic plaques, diffuse plaques, and neurofibrillary tangles in a 1-mm2 area sampled from 4 cortical regions was counted, and a global measure of AD pathology (range, 0-2.98 U) and specific measures of each pathology were derived. Main outcome measures Clinical diagnosis of probable AD and level of global cognitive function at the last evaluation before death. Results Women had more global AD pathology than did men (P = .04), due primarily to more neurofibrillary tangles (P = .02). At the last evaluation before death, 57 persons met clinical criteria for probable AD (34 [60%] of them women). In logistic regression models, sex was not related to odds of clinical AD (odds ratio [OR], 1.35; 95% confidence interval [CI], 0.56-3.25), but the relation of global AD pathology to clinical diagnosis differed for men and women. Each additional unit of AD pathology was associated wit…
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Women develop greater neurofibrillary degeneration, brain parenchymal loss, and cognitive decline.
“Recent studies suggest that women develop greater neurofibrillary degeneration, brain parenchymal loss, and cognitive decline.52,53,54”
From Sex differences in cognitive decline among US adults (2021) · cites this paper as [52]
In earlier work, women had more AD pathology and neurofibrillary tangles in particular, but not neuritic or diffuse plaques, among 141 subjects who came to autopsy.
“Also, in earlier work, we found that women had more AD pathology and neurofibrillary tangles in particular, but not neuritic or diffuse plaques, among 141 subjects who came to autopsy [8].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [8]
The association of Alzheimer's disease pathology with clinical manifestations is more significant in women than in men.
“The association of AD pathology with clinical manifestations of the disease is also more significant in women than men [4].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [4]
Women with Alzheimer's disease show faster brain volume loss than men.
“Women with AD show greater cognitive vulnerability to AD pathology, steeper rates of cognitive decline, and faster brain volume loss than men do [4, 5].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [4]
Women with Alzheimer's disease show greater cognitive vulnerability to Alzheimer's disease pathology than men.
“Women with AD show greater cognitive vulnerability to AD pathology, steeper rates of cognitive decline, and faster brain volume loss than men do [4, 5].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [4]
Women with Alzheimer's disease show steeper rates of cognitive decline than men.
“Women with AD show greater cognitive vulnerability to AD pathology, steeper rates of cognitive decline, and faster brain volume loss than men do [4, 5].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [4]
Women exhibit increased global Alzheimer's neuropathological burden and greater cognitive impairment compared to men.
“However, despite their prolonged survival, even with Alzheimer’s disease [7–9], women exhibit increased global Alzheimer’s neuropathological burden and greater cognitive impairment [10–13].”
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- Authors
- Barnes, L. L., Wilson, R. S., Bienias, J. L., Schneider, J. A., Evans, D. A., & Bennett, D. A.
- Affiliations
- Rush University Medical Center (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2005-06-01
- Volume
- 62
- Issue
- 6
- Pages
- 685
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2042778267
- Cited by
- 643
- References
- 15
- Citations by year
- 2026: 40 · 2025: 71 · 2024: 75 · 2023: 53 · 2022: 41 · 2021: 54 · 2020: 32 · 2019: 32 · 2018: 33 · 2017: 19 · 2016: 35 · 2015: 26 · 2014: 17 · 2013: 11 · 2012: 24
- FWCI
- 6.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30-AG 10161, R01 AG15819, R01AG015819, P30AG010161, KO8 AG00849, K08AG000849)
- 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 › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- Alzheimer's disease, sex differences, neuropathology, clinical features, neurofibrillary tangles, neuritic plaques, diffuse plaques, dementia, cognitive function, brain autopsy, clinicopathological correlation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Brain, Cognition Disorders, Female, Genotype, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Risk Factors, Sex Factors, Cohort Studies, Confidence Intervals, Odds Ratio, Neurofibrillary Tangles, Lewy Body Disease, Plaque, Amyloid
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