Sex Difference in the Association of APOE4 with Memory Decline in Mild Cognitive Impairment
Abstract
Our aim was to examine whether the influence of apolipoprotein E4 (APOE4) genotype on cognitive decline differs in male and female across the Alzheimer’s disease (AD) continuum. Among individuals with normal cognition (NC; n = 415), mild cognitive impairment (MCI; n = 870), and AD ( n = 334), we investigated the longitudinal associations of APOE4 genotype and sex with cognitive decline over 13 years. Our cognitive outcomes were Rey Auditory Verbal Learning Test (RAVLT) total learning score and delayed recall and Mini-Mental State Examination (MMSE) score. There were significant effects of the APOE4×sex interaction on change in verbal memory in the MCI group, but not the NC or AD group. Specifically, among individuals with MCI, female APOE4 carriers had a steeper decline in RAVLT total learning score, but not delayed recall or MMSE score compared to all other groups (APOE4 + /Male, APOE4-/Female, APOE4-/Male). In conclusion, female APOE4 carriers have faster rates of memory decline than their male counterparts among MCI individuals.
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Women are more vulnerable to effects of APOE4 on memory decline, risk for AD dementia, and neuropathology.
“Women are more vulnerable to effects of APOE4 on memory decline [45] as well as risk for AD dementia [16] and neuropathology [46], and more limited data suggest that APOE2 also confers greater protection against AD risk for women than men [16].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [45]
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References 32 · Cited by 51
- Authors
- Wang, X., Zhou, W., Ye, T., Lin, X., Zhang, J., & Initiative, F. A. D. N.
- Affiliations
- Wenzhou Seventh People's Hospital (CN)
- Hangzhou Normal University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Independent Researcher, Hangzhou, China
- Corresponding author
- Lin, Xiaodong
- Zhang, Jie
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2019-05-20
- Volume
- 69
- Issue
- 4
- Pages
- 1161-1169
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2946151933
- Cited by
- 51
- References
- 32
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 14 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 2
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904)
- 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 › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- APOE ε4, sex differences
- MeSH terms
- Mental Status and Dementia Tests, Aged, Female, Genotype, Humans, Longitudinal Studies, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Sex Factors, Case-Control Studies, Disease Progression, Apolipoprotein E4, Cognitive Dysfunction
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