Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study

Abstract

An elevated blood concentration of homocysteine is an established risk factor for cognitive impairment and dementia, but associations between cognition and methylmalonic acid (MMA), a related metabolic marker of vitamin B-12 deficiency, are less clear. The aim was to determine the utility of serum MMA and holotranscobalamin as markers of vitamin B-12 status in relation to cognitive function and to investigate their association with discrete cognitive domains. This was a cross-sectional survey of 84 nondemented elderly participants (aged >69 y) from the Welsh cohort of the Medical Research Council's Cognitive Function and Ageing Study. Cognitive status was determined by Mini-Mental State Examination (MMSE) and the Cognitive Section of the Cambridge Mental Disorders of the Elderly Examination (CAMCOG). Nearly one-half (43%) of the persons selected had likely metabolically significant vitamin B-12 deficiency. Higher MMA concentrations were associated with lower MMSE scores independent of age and education (P = 0.007). MMA concentration correlated inversely with CAMCOG scores of ideational praxis (P < 0.05) and language comprehension (P < 0.05) and expression (P < 0.01). Serum folate correlated weakly but significantly with language (P < 0.05), remote memory (P < 0.05), and constructional and ideational praxis scores (P < 0.05 and P < 0.01, respectively). The high prevalence of likely metabolically significant vitamin B-12 deficiency in the elderly is associated with lower cognitive function scores and particularly with lower scores of language comprehension and expression.