title: Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline.
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.
authors.affiliation: National Institute on Aging, NIA/NIH/IRP, Baltimore, MD 21224, USA. baydounm@mail.nih.gov
authors.forename: May A
authors.initials: MA
authors.lastname: Beydoun
authors.forename: Adel
authors.initials: A
authors.lastname: Boueiz
authors.forename: Marwan S
authors.initials: MS
authors.lastname: Abougergi
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Kitner-Triolo
authors.forename: Hind A
authors.initials: HA
authors.lastname: Beydoun
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4