Abstract
Background: Evidence suggests that APOE epsilon 4 carriers haveworse memory performances compared to APOE epsilon 4 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 epsilon 4 on cognition.
Objective: To investigate whether associations between APOE epsilon 4 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 epsilon 4 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 epsilon 4 female carriers with slow rates of GrimAge had significantly better memory performances compared to fast and average aging APOE epsilon 4 female carriers. Therewas 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 epsilon 4 carriers or non-carriers.
Conclusion: Slower rates of aging in female APOE epsilon 4 carriers may buffer against the negative effects of the epsilon 4 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 epsilon 4 carriers.