DNA methylation and cognitive functioning in healthy older adults

Abstract

Long-term supplementation with folic acid may improve cognitive performance in older individuals. The relationship between folate status and cognitive performance might be mediated by changes in methylation capacity, as methylation reactions are important for normal brain functioning. Although aberrant DNA methylation has been implicated in neurodevelopmental disorders, the relationship between DNA methylation status and non-pathological cognitive functioning in humans has not yet been investigated. The present study investigated the associations between global DNA methylation and key domains of cognitive functioning in healthy older adults. Global DNA methylation, defined as the percentage of methylated to total cytosine, was measured in leukocytes by LC-MS/MS, in 215 men and women, aged 50-70 years, who participated in the FACIT study (clinical trial registration number NCT00110604). Cognitive performance was assessed by means of the Visual Verbal Word Learning Task, the Stroop Colour-Word Interference Test, the Concept Shifting Test, the Letter-Digit Substitution Test, and the Verbal Fluency Test. Using hierarchical linear regression analyses adjusted for age, sex, level of education, alcohol consumption, smoking status, physical activity, erythrocyte folate concentration, and MTHFR677C→T genotype, global DNA methylation was not related to cognitive performance on any of the domains measured. Our results do not support the hypothesis that global DNA methylation, as measured in leukocytes, might be associated with cognitive functioning in healthy older individuals.