Female APOE ɛ4 Carriers with Slow Rates of Biological Aging Have Better Memory Performances Compared to Female ɛ4 Carriers with Accelerated Aging

Background: Evidence suggests that APOE ɛ4 carriers have worse memory performances compared to APOE ɛ4 non-carriers and effects may vary by sex and age. Estimates of biological age, using DNA methylation may enhance understanding of the associations between sex and APOE ɛ4 on cognition. Objective: To investigate whether associations between APOE ɛ4 status and memory vary according to rates of biological aging, using a DNA methylation age biomarker, in older men and women without dementia. Methods: Data were obtained from 1,771 adults enrolled in the 2016 wave of the Health and Retirement Study. A series of ANCOVAs were used to test the interaction effects of APOE ɛ4 status and aging rates (defined as 1 standard deviation below (i.e., slow rate), or above (i.e., fast rate) their sex-specific mean rate of aging on a composite measure of verbal learning and memory. Results: APOE ɛ4 female carriers with slow rates of GrimAge had significantly better memory performances compared to fast and average aging APOE ɛ4 female carriers. There was no effect of aging group rate on memory in the female non-carriers and no significant differences in memory according to age rate in either male APOE ɛ4 carriers or non-carriers. Conclusion: Slower rates of aging in female APOE ɛ4 carriers may buffer against the negative effects of the ɛ4 allele on memory. However, longitudinal studies with larger sample sizes are needed to evaluate risk of dementia/memory impairment based on rates of aging in female APOE ɛ4 carriers.