Because it's a randomized controlled trial (RCT) rather than an observational study, it's showing causation rather than mere correlation. I imagine the correlations between ω-3 fatty acids (more is better) and homocysteine (less is better) inspired the RCT, but I think the authors do well not to include homocysteine in their conclusions. I love that they avoided fish oil supplementation and simply measured ω-3 fatty acids as it really adds to clarity regarding the value of B vitamin supplementation.
Alas, there's no ε4 breakout.
For my part, I have been betting on the hypothesis that keeping homocysteine below the high end of the reference range with B vitamins, TMG, and NAC; consuming sardines, salmon, grass fed beef, omega-3 eggs, and cod liver oil; and avoiding high omega-6 processed seed oils will be good for me. This paper doesn't prove that my strategy is right, but it certainly bolsters my resolve to continue.
Design: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations.
Results: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group.
Conclusions: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status.