Key result
Female APOE4 status in MCI linked to steeper 13-year cognitive decline versus other groups.
Why the study?
The influence of APOE4 genotype on cognitive decline may differ by sex across the Alzheimer's disease continuum, but this relationship is not well characterized.
Does the interaction between APOE4 genotype and sex affect the rate of memory decline in individuals with mild cognitive impairment?
Cohort (n=1,619)
Does the interaction between APOE4 genotype and sex affect the rate of memory decline in individuals with mild cognitive impairment?
Female APOE4 carriers with mild cognitive impairment experience faster rates of memory decline than their male counterparts, highlighting a sex-specific genetic risk factor for cognitive decline.
Answers are grounded in this paper and cite their sources.
Female APOE4 carriers with MCI showed faster verbal memory decline; supports sex-stratified analyses in research but should not yet change practice.
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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Wang et al. (2019) conducted a cohort in Alzheimer's disease continuum (Normal cognition, Mild cognitive impairment, Alzheimer's disease) (n=1,619). APOE4 genotype and female sex vs. Male APOE4 carriers, and male/female APOE4 non-carriers was evaluated on Cognitive decline (Rey Auditory Verbal Learning Test total learning score and delayed recall, and Mini-Mental State Examination score). Among individuals with mild cognitive impairment, female APOE4 carriers had a significantly steeper decline in RAVLT total learning score over 13 years compared to all other groups.
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