Sex differences in cognitive impairment in Alzheimer’s disease
Open accessAbstract
Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer's disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.
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Females with MCI or AD dementia show greater cognitive decline and are outperformed by males in several cognitive domains.
“Research has shown that females with MCI or AD dementia shows greater cognitive decline and are outperformed by males in several cognitive domains. 68 , 69”
From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [69]
The Conclusion (page not provided) says men with AD outperform women across multiple cognitive domains, and a later passage says female patients with MCI show increased vulnerability to cognitive impairment earlier in the illness. But the Conclusion describes evidence that females deteriorate faster as limited and calls for longitudinal studies; the claim presents greater cognitive decline across MCI or AD dementia more definitively than the review does. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNotable sex differences in the clinical and pathological presentation between the sexes exist.
“Notable sex differences in the clinical and pathological presentation between the sexes exist, each of which have been extensively reviewed previously [258–261]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [261]
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- Authors
- Laws, K. R., Irvine, K., & Gale, T. M.
- Affiliations
- University of Hertfordshire (GB)
- Corresponding author
- Laws, Keith R
- Venue
- World Journal of Psychiatry
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2016
- Volume
- 6
- Issue
- 1
- Pages
- 54
- ISSN
- 2220-3206 (ISSN-L)
- PMC
- PMC4804268
- OpenAlex
- W2328745627
- Cited by
- 307
- References
- 145
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 38 · 2023: 32 · 2022: 40 · 2021: 41 · 2020: 29 · 2019: 26 · 2018: 24 · 2017: 17 · 2016: 7
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Psychiatry (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (acceptedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion, cc-by-nc)
- 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 › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- Alzheimer's disease, sex differences, cognitive impairment, women, estrogen, postmenopausal women, cognitive reserve, APOE ε4, episodic memory, visuospatial ability, dementia diagnosis
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