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Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C>G, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants. Of all the studied polymorphisms, only MTHFR 677C>T was associated with homocysteine concentration. No significant relationship was observed for any of the polymorphisms with cognitive performance or severity of cerebral white matter lesions.

Original publication




Journal article


Neurobiol Aging

Publication Date





2020 - 2022


5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase, Aged, Aged, 80 and over, Aging, Brain, Cognition, Cross-Sectional Studies, Cystathionine beta-Synthase, Ferredoxin-NADP Reductase, Homocysteine, Humans, Methylenetetrahydrofolate Reductase (NADPH2), Middle Aged, Nerve Fibers, Myelinated, Reduced Folate Carrier Protein, Transcobalamins