British Journal of Nutrition

Human and Clinical Nutrition

DNA methylation and cognitive functioning in healthy older adults

Olga J. G. Schiepersa1 c1, Martin P. J. van Boxtela1, Renate H. M. de Groota1a2a3, Jelle Jollesa1a2, Frans J. Koka4, Petra Verhoefa4a5a6 and Jane Durgaa4a5a7

a1 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS)/European Graduate School of Neuroscience (EURON), Maastricht University/Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht, The Netherlands

a2 Faculty of Psychology and Education, AZIRE Research Institute, VU University Amsterdam, Amsterdam, The Netherlands

a3 Centre for Learning Sciences and Technologies, Open University, Heerlen, The Netherlands

a4 Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

a5 Top Institute Food and Nutrition, Wageningen, The Netherlands

a6 Unilever Research and Development, Vlaardingen, The Netherlands

a7 Cognitive Sciences Group, Nutrition and Health Department, Nestlé Research Centre, Lausanne, Switzerland


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 functioning of the brain. Although aberrant DNA methylation has been implicated in neurodevelopmental disorders, the relationship between DNA methylation status and non-pathological cognitive functioning in human subjects 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 cytosine to total cytosine, was measured in leucocytes by liquid chromatography–MS/MS, in 215 men and women, aged 50–70 years, who participated in the Folic Acid and Carotid Intima-Media Thickness (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 5,10-methylenetetrahydrofolate reductase 677 C → T genotype, we found that global DNA methylation was not related to cognitive performance on any of the domains measured. The present study results do not support the hypothesis that global DNA methylation, as measured in leucocytes, might be associated with cognitive functioning in healthy older individuals.

(Received March 04 2011)

(Revised May 23 2011)

(Accepted June 02 2011)

(Online publication July 27 2011)


c1 Corresponding author: O. J. G. Schiepers, fax +31 433884092, email


Abbreviations: FACIT, Folic Acid and Carotid Intima-Media Thickness (FACIT); MTHFR, 5,10-methylenetetrahydrofolate reductase