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Cited by 270Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchSex and Gender in Healthcare

Sexual dimorphism in predisposition to Alzheimer's disease

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Fisher, Daniel W., Bennett, David A., Dong, Hongxin·2018·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2018.04.004PMC PMC6368179
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Abstract

Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and rate of symptom progression, but the mechanisms underlying this sexual divergence are unknown. Although some have suggested this difference in risk is a reflection of the known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities toward the disease. Although a number of potential risk factors have been hypothesized to mediate these differences, none have been definitively verified. In this review, we first summarize the epidemiologic studies of prevalence and incidence of AD among the sexes. Next, we discuss the most likely risk factors to date that interact with biological sex, including (1) genetic factors, (2) sex hormones (3) deviations in brain structure, (4) inflammation and microglia, and (5) and psychosocial stress responses. Overall, though differences in life span are likely to account for part of the divide between the sexes in AD prevalence, the abundance of preclinical and clinical evidence presented here suggests an increase in intrinsic AD risk for women. Therefore, future studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD pathogenesis in both sexes, with the eventual goal of sex-specific prevention and treatment strategies.

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Crossref · 10.1016/j.neurobiolaging.2018.04.004

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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 [97]

    The Epidemiologic perspective says AD prevalence is often reported as higher in women, but notes that women's greater longevity complicates comparisons of age-matched risk. It also says some evidence suggests faster progression in women, while other studies find no association or are inconclusive. The unqualified claim overstates the evidence for symptom progression. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Mounting evidence suggests that women are at heightened risk for exhibiting Alzheimer disease pathophysiology.

    “although mounting evidence suggests that women are at heightened risk for exhibiting AD pathophysiology.5–8”

    From Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults (2019) · cites this paper as [8]

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Authors
Fisher, D. W., Bennett, D. A., & Dong, H.
Affiliations
  • Northwestern University (US)
  • Rush University Medical Center (US)
Corresponding author
Dong, Hongxin
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2018-10
Volume
70
Pages
308-324
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2018.04.004
PMC
PMC6368179
OpenAlex
W2801203507
Cited by
270
References
184
Citations by year
2026: 27 · 2025: 37 · 2024: 43 · 2023: 40 · 2022: 39 · 2021: 32 · 2020: 26 · 2019: 19 · 2018: 7
FWCI
2.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (RF1AG057884, P30AG010161, R56AG053491)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
Keywords
Alzheimer's disease, sex differences, sexual dimorphism, women, disease prevalence, incidence, sex hormones, genetic risk factors, brain structure, neuroinflammation, microglia, psychosocial stress
MeSH terms
Alzheimer Disease, Apolipoproteins E, Female, Humans, Male, Risk Factors, Sex Characteristics, Gonadal Steroid Hormones, Brain-Derived Neurotrophic Factor

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