Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study.

J Intern Med. 2012 Feb;271(2):204-12. doi: 10.1111/j.1365-2796.2011.02484.x. Epub 2011 Dec 30.



To examine the associations between serum homocysteine (tHcy), holotranscobalamin (holoTC, the biologically active fraction of vitamin B12) and folate and cognitive functioning in a longitudinal population-based study of Finnish elderly subjects.


tHcy, holoTC and folate were measured at baseline in 274 dementia-free subjects aged 65-79years from the Cardiovascular Risk Factors, Aging and Dementia study. Subjects were re-examined 7years later, and global cognition, episodic memory, executive functioning, verbal expression and psychomotor speed were assessed.


Higher baseline tHcy levels were associated with poorer performance in global cognition, relative difference: 0.90 [95% confidence interval (CI) 0.81-0.99]; episodic memory: 0.87 (95% CI 0.77-0.99); executive functions: 0.86 (95% CI 0.75-0.98); and verbal expression: 0.89 (95% CI 0.81-0.97) at follow-up. Increased holoTC levels were related to better performance on global cognition: 1.09 (95% CI 1.00-1.19); executive functions: 1.11 (95% CI 1.01-1.21); and psychomotor speed: 1.13 (95% CI 1.01-1.26). After excluding 20 cases of incident dementia, increased tHcy remained associated with poorer performance in episodic memory, execution functions and verbal expression. Higher holoTC levels tended to be related to better performance in executive functions and psychomotor speed, while elevated serum folate concentrations were significantly related to higher scores in global cognition and verbal expression tests.


tHcy, holoTC and folate levels are related to cognitive performance 7years later even in nondemented elderly subjects. Randomized trials are needed to determine the impact of vitamin B12 and folate supplementation on preventing cognitive decline in the elderly.


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