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Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study ^1,2,3

¹ From the Gerontological Research Programme, Faculty of Medicine, National University of Singapore, Singapore (LF, T-PN, LC, and MN); the Department of Psychological Medicine, National University of Singapore, Singapore (LF, T-PN, and E-HK); and the Cognitive Neuroscience Laboratory, Singapore Health Service, Singapore (LC)

Background: The relations of elevated homocysteine, low folate, and vitamin B-12 with cognitive performance in nondemented elderly are not well established. Limited research data suggest differential effects of homocysteine and folate on specific cognitive domains.

Objective: The aim was to examine the independent associations of homocysteine, folate, and vitamin B-12 with cognitive performance in high-functioning elderly Chinese.

Design: Homocysteine, folate, and vitamin B-12 concentrations were measured in fasting blood samples of 451 Chinese aged 55 y with Mini-Mental State Examination scores 24 and who were considered fully independent based on Activities of Daily Living score. Cognitive functions were assessed by a neuropsychological test battery. Independent associations (standardized ß) were determined in multiple linear regression models that simultaneously controlled for potential confounders.

Results: Log-transformed homocysteine was inversely associated with performance on Block Design (ß = –0.319, P = 0.006) and the written Symbol Digit Modality Test (ß = –0.129, P = 0.031). Log-transformed folate was significantly associated with Rey Auditory Verbal Learning Test delayed recall (ß = 0.139, P = 0.010), verbal learning (ß = 0.112, P = 0.038), percentage of forgetting (ß = –0.139, P = 0.013), and the Categorical Verbal Fluency test (ß = 0.104, P = 0.042). Vitamin B-12 was not significantly associated with any cognitive test score.

Conclusions: In this high-functioning elderly Chinese population, elevated homocysteine is associated with deficits in constructional ability and processing speed and folate is associated with measures of episodic memory and language. Our results provide support for differential effects of homocysteine and folate on specific cognitive functions.

Key Words: Homocysteine • folate • vitamin B-12 • cognitive function • Chinese