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Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study^1,2,3

¹ From the University Department of Psychiatry, Royal Liverpool University Hospital, Liverpool, United Kingdom (CM); the Department of Pathology, Wrexham Maelor Hospital, Wrexham, United Kingdom (PH); the University Hospital of Wales, Cardiff, United Kingdom (RE); and the Wales College of Medicine, Division of General Practice, Wrexham, United Kingdom (AM)

Background: 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.

Objective: 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.

Design: 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).

Results: 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).

Conclusion: 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.

Key Words: Vitamin B-12 • methylmalonic acid • holotranscobalamin • cognitive function • Mini-Mental State Examination • folate • elderly • aging • basal ganglia • language

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