Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline
Tangney, C.C., Tang, Y., Evans, D.A., and Morris,
M.C.Neurology – 27-JAN-2009; 72(4): 361-7
Objectives: The goal of the study was to determine which parameters—serum concentrations of Vitamin B12 or B12 metabolites were most closely correlated with cognitive decline.
Methods: A stratified random sampling selected 516 subjects from the Chicago Health and Aging Project. Linear mixed models were used to examine the association of homocysteine, methylmalonic acid, 2-methylcitric acid, and cystathionine to a change in cognitive scores. The time frame of the study was over 6 years. Every three years during this period, cognitive function was assessed by the East Boston tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. On each test, scores were expressed as z-scores and averaged. An approximately normally distributed global measure of cognitive function was obtained. The statistical analysis reduced the “floor and ceiling effects” as well as other potential measurement errors inherent in each test. Results were expressed as the sum of the standardized scores.
Results: Vitamin B12 deficiency was seen in 14.2% of the participants. Increased serum homocysteine was noted in 19.2% while increased methylmalonic (MMA) acid levels were noted in 36.4% of participants. The higher MMA values were correlated with faster cognitive decline (p = 0.004). Conversely, higher B12 concentrations were associated with slower rates of cognitive decline. (p = 0.005) There was no detectable relationship between homocysteine levels and cognition.
Conclusions: The most important risk factors for cognitive decline in older populations are high serum methylmalonic acid and low vitamin B12 concentrations. Supplementation with folic acid, in food or as a supplement, may be contraindicated in this population.