DNA Methylation Impacts on Cognitive Decline in a Cohort of Elderly Men

Abstract

ISEE-0568 Background and Objective: Environmental exposures have been associated with both epigenetic mechanisms and decrements in cognitive function. Epigenetic phenomena regulate the normal function of cells, including neurons, while epigenetic dysregulation has been identified in cognitive function disorders. The role of DNA methylation on changes in cognitive function over time has not been investigated. The objective of the current study was to evaluate whether DNA methylation in repetitive elements widely represented across the human genome is associated with changes in cognitive function in normal aging individuals. Methods: A longitudinal cohort study was conducted in the context of the Normative Aging Study (Boston, USA) among 646 community-dwelling elderly men who underwent a battery of cognitive tests and who also had DNA methylation measurements. We used mixed effects models to assess the association between repeated measurements of scores on a battery of cognitive tests over time and DNA methylation in Alu and LINE-1 (long interspersed nucleotide element-1) repetitive elements. Cognitive testing was performed from 1993 through 2007 and a total of 1,659 observations were included in the final analysis. Results: The mean age of participants at baseline visit was 67.7 (SD = 7) years and the mean number of years of education was 14.4 (SD = 2.7). In multivariable models, a statistically significant greater decrease on a working memory test score (digit span backward test) over time with increasing LINE-1 DNA methylation (b = −0.019, P = 0.0397) was found. A decline in performance over time was observed on the majority of the tests as DNA methylation increased but the associations did not reach statistical significance. Conclusion: Higher levels of DNA methylation in LINE-1 repetitive elements may adversely affect cognitive function, particularly in the working memory domain.