Beneficial Interactions Between B Vitamins and Omega-3 Fatty Acids in the Prevention of Brain Atrophy and of Cognitive Decline in Early Stage Alzheimer's Disease

Abstract

Background and aim

A randomised trial (VITACOG) in people with Mild Cognitive Impairment (MCI), a prodromal stage of Alzheimer's disease, found that B vitamin treatment to lower homocysteine slowed the rate of brain atrophy and of cognitive and clinical decline. (de Jager et al. Int J. Geriatr. Psychiatry 2012, 27:592–600; Douaud et al. PNAS 2013, 110:9523–28). We reported last year that, in this trial, B vitamins only slowed brain atrophy in subjects with a good baseline omega-3 fatty acid status (Jerneren et al. AJCN 2015; 102:215–21). We have now used data from the trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment on cognitive and clinical outcomes.

Methods

266 participants with MCI aged ≥70 years were randomised to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured.

Results

Final scores for episodic memory, global cognition and CDR sum-of-boxes were better in the B vitamin-treated group as the baseline concentration of omega-3 fatty acids increased, whereas scores in the placebo group did not change across omega-3 concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 (i.e., worse) after 2 years compared with 59% among those on placebo; in other words, nearly twice as many on placebo progressed towards Alzheimer's disease as those on B vitamins with good omega-3 status. For all 3 outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins. Eicosapentaenoic acid showed a similar pattern but did not reach significance.

Conclusions

When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range B vitamins interact to slow cognitive and clinical decline. These findings on cognition mirror the earlier findings on brain atrophy, consistent with a disease-modifying effect of the combination of the two nutrients. We suggest that one mechanism for this beneficial interaction may be that B vitamins are needed for the methylation of phosphatidylethanolamine to give phosphatidylcholine (enriched in omega-3 fatty acids), which plays a key role both in brain structure and in synaptic function. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.

Support or Funding Information

Supported by grants from Norman Collisson Foundation, Medical Research Council, Charles Wolfson Charitable Trust