Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian population with dementia

Hyperhomocysteinemia is a known risk factor for vascular disease and common ly occurs in the elderly. Several studies have shown an association between elevated plasma homocysteine levels and cognitive impairment, indicating t hat it may play a role in the pathophysiology of dementia. We studied plasm a homocysteine, folate, vitamin B12 levels and the MTHFR C677T genotype in an Italian population of patients with dementia. We confirmed that elevated plasma tHcy (> 14 mu mol/l) is common in elderly subjects with dementia. A lthough we found a high prevalence of the MTHFR TT genotype (21.2%) the all ele frequency is not over-represented relative to the control population. W e also observed a high incidence of folate deficiency (38%) in subjects wit h dementia. Elevated homocysteine was associated with low plasma folate ( < 5.7 nmol/1) and the MTHFR TT genotype. Moderate to severe hyperhomocystein emia ( > 26.1 nmol/1) was associated with a significantly lower MMSE score. Hyperhomocysteinemia may be neurotoxic by several different mechanisms aff ecting cognitive function. Further studies are needed to fully explore the potential of B vitamin supplementation to lower plasma homocysteine and imp rove cognitive function. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.