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DNA methylation and cognitive functioning in healthy older adults


Schiepers, Olga J. G., van Boxtel, Martin P. J., de Groot, Renate H. M., Jolles, Jelle, Kok, Frans J., Verhoef, Petra, Durga, Jane


The British Journal Of Nutrition, Volume: 107, No.: 5, Pages.: 744-748

Year of Publication



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.;

Bibtex Citation

@article{Schiepers_2011, doi = {10.1017/s0007114511003576}, url = {}, year = 2011, month = {jul}, publisher = {Cambridge University Press ({CUP})}, volume = {107}, number = {05}, pages = {744--748}, author = {Olga J. G. Schiepers and Martin P. J. van Boxtel and Renate H. M. de Groot and Jelle Jolles and Frans J. Kok and Petra Verhoef and Jane Durga}, title = {{DNA} methylation and cognitive functioning in healthy older adults}, journal = {British Journal of Nutrition} }


510methylenetetrahydrofolate reductase fadh2, aged, aging, blood, crosssectional studies, cytosine, dna methylation, doubleblind method, erythrocytes, etiology, female, folate, folic acid, folic acid deficiency, genetic association studies, genetics, homocysteine, humans, leukocytes, male, metabolism, middle aged, mild cognitive impairment, physiopathology, polymorphism single nucleotide, psychiatric status rating scales, psychology, status

Countries of Study


Types of Dementia

Mild Cognitive Impairment (MCI)

Types of Study

Cohort Study

Type of Outcomes


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population