Metabolic Markers of Cobalamin Deficiency and Cognitive Function in Normal Older Adults

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Abstract
Objectives: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. Design: Cross‐sectional study. Setting: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. Participants: Two hundred eighty‐one cognitively normal, community‐dwelling participants aged 65 and older. Measurements: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). Results: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (β=−0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores. Conclusion: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.