B Vitamin Supplementation Slows Cognitive Decline in Mild Cognitive Impairment Patients with Frontal Lobe Atrophy

Abstract

Background: The effects of B vitamins on mild cognitive impairment (MCI) patients’ cognition have been mixed, suggesting the existence of moderating factors. Objective: A post hoc analysis of a negative B vitamin trial was performed to examine the potential modulating effect of regional brain atrophy on the cognitive response to B vitamins in MCI patients. Methods: In the 24-month randomized trial, 279 MCI outpatients took 500μ#x03BC;g methylcobalamin and 400μ#x03BC;g folic acid once per day or placebo tablets once per day. Sixty-four aspirin users were excluded from analysis as aspirin use has been found to have significant negative interaction effects. Subjects were followed up at months 12 and 24. The primary cognitive outcome was clinical dementia rating scale sum of boxes (CDR_SOB). In a subgroup of 83 subjects, MRI brain scans were performed at baseline to estimate regional brain atrophy ratios. Results: Among the trial subjects who had MRI data, B vitamin supplementation had no significant effect on CDR_SOB, despite having significant homocysteine lowering effects. The atrophy ratio of the left frontal lobe significantly moderated the effect of B vitamin supplementation on CDR_SOB, after adjusting for confounders, in that B vitamin supplementation was associated with lower CDR_SOB scores (i.e., better cognitive function) at the 24th month among those patients with above median atrophy ratios, but not among those with lower atrophy ratios, in the left frontal lobe. Conclusion: B vitamins may be more effective in slowing down cognitive decline in MCI patients with atrophy in the left frontal lobe.