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Cited by 139Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCognitive Abilities and Testing

Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline

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Beydoun, May A., Boueiz, Adel, Abougergi, Marwan S., Kitner-Triolo, Melissa H., Beydoun, Hind A., Resnick, Susan M., O'Brien, Richard, Zonderman, Alan B.·2012·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2010.05.017PMC PMC2974952
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Abstract

We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4(+) predicted dementia significantly (hazard ratio [HR] = 2.89; 95% confidence interval [CI], 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4(+) status and impairment or decline on the California Verbal Learning Test (CVLT; delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 × sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4(+) status remained stronger among women, though only before Bonferroni correction. While ApoE4(+) status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women.

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  • Epidemiologic studies show sex differences in clinical risk are largely discernable within the context of APOE ε4, particularly between the ages of 65 to 75 years compared with APOE ε4 clinically normal male carriers.

    “Epidemiologic studies show sex differences in clinical risk are largely discernable within the context of APOE ε4,11,42,43 particularly between the ages of 65 to 75 years compared with APOE ε4 clinically normal male carriers.44”

    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 [42]

    The Results and Discussion (pages unavailable) report stronger APOE ε4 associations with some cognitive outcomes in women than men, although the sex difference in dementia risk was not statistically significant. The Results also note higher dementia incidence among carriers by age 75, but do not establish a sex difference specifically at ages 65–75 or a comparison with clinically normal male carriers. (LLM, conf=0.85)

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Authors
Beydoun, M. A., Boueiz, A., Abougergi, M. S., Kitner-Triolo, M. H., Beydoun, H. A., Resnick, S. M., O'Brien, R., & Zonderman, A. B.
Affiliations
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
  • Eastern Virginia Medical School (US)
Corresponding author
Beydoun, May A.
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2012-04
Volume
33
Issue
4
Pages
720-731.e4
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2010.05.017
PMC
PMC2974952
OpenAlex
W2021411451
Cited by
139
References
78
Citations by year
2026: 4 · 2025: 4 · 2024: 14 · 2023: 18 · 2022: 13 · 2021: 13 · 2020: 10 · 2019: 19 · 2018: 12 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 2 · 2013: 3 · 2012: 2
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Demensförbundet
  • Eastern Virginia Medical School
  • National Institutes of Health (Z99 AG999999)
  • National Institute on Aging (ZIAAG000185)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
APOE ε4, sex differences, dementia, cognitive impairment, cognitive decline, verbal memory, verbal learning, effect modification, genetic risk factors, aging
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Analysis of Variance, Cognition Disorders, Dementia, Female, Gene Frequency, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Surveys and Questionnaires, Mental Recall, Sex Characteristics, Incidence, Kaplan-Meier Estimate, Apolipoprotein E4, Young Adult, Genetic Association Studies

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