Understanding the impact of sex and gender in Alzheimer’s disease: A call to action
Open accessAbstract
INTRODUCTION: Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches. METHODS: The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD. RESULTS: The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research. DISCUSSION: The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
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Alzheimer's disease prevalence and symptom progression are disproportionately higher in women.
“AD disease prevalence and symptom progression are disproportionately higher in women [97,98,99].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [98]
The Introduction reports that more women than men live with an AD diagnosis, but distinguishes that count from prevalence: studies of sex differences in prevalence are mixed, and a global meta-analysis found no significant difference. The Clinical presentation section reports faster cognitive and clinical decline among women with MCI, supporting the progression part of the claim for that group, not as an unqualified statement about all women with AD. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSex is a strong factor underlying phenotypic variability in AD.
“As sex is a strong factor underlying phenotypic variability in AD”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [6]
Sex differences have been observed in the progression, diagnosis, and clinical presentations of AD.
“Despite the mixed findings from these incidence studies, sex differences have been observed in the progression, diagnosis, and clinical presentations of AD.”
From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [13]
In adults over 65, the risk of AD in women is twice as high as in men.
“In the Framingham Study cohort, a study conducted in individuals aged between 65 and 100 years old, incidence of AD in women was twice as high as men [41]”
From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [41]
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References 143 · Cited by 839
- Authors
- Nebel, R. A., Aggarwal, N. T., Barnes, L. L., Gallagher, A., Goldstein, J. M., Kantarci, K., Mallampalli, M. P., Mormino, E. C., Scott, L., Yu, W. H., Maki, P. M., & Mielke, M. M.
- Affiliations
- Society for Women's Health Research (US)
- Rush University Medical Center (US)
- Harvard University (US)
- Mayo Clinic (US)
- Stanford Medicine (US)
- Johns Hopkins University (US)
- Columbia University (US)
- University of Illinois Chicago (US)
- Corresponding author
- Nebel, Rebecca A.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-06-12
- Volume
- 14
- Issue
- 9
- Pages
- 1171-1183
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6400070
- OpenAlex
- W2808227793
- Cited by
- 839
- References
- 143
- Citations by year
- 2026: 103 · 2025: 119 · 2024: 141 · 2023: 139 · 2022: 110 · 2021: 102 · 2020: 68 · 2019: 48 · 2018: 9
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Novartis
- Amgen
- Johnson and Johnson
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, sex differences
- MeSH terms
- Alzheimer Disease, Animals, Gender Identity, Humans, Sex Characteristics
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