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Randomized Controlled Trial
. 2016;50(2):547-57.
doi: 10.3233/JAD-150777.

Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment

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Free PMC article
Randomized Controlled Trial

Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment

Abderrahim Oulhaj et al. J Alzheimers Dis. .
Free PMC article

Abstract

A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized 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. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. 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 decline. 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.

Keywords: Alzheimer’s disease; B vitamins; clinical dementia rating scale; cognition; omega–3 fatty acids.

Figures

Fig.1
Fig.1
Episodic memory score after 2 years according to baseline omega-3 fatty acid concentration. The interaction between omega-3 tertiles and B vitamin treatment was significant (p = 0.028). In the third tertile of the combined omega-3 fatty acid concentration, the memory score in the B vitamin group was higher than in placebo (p = 0.047). In the B vitamin group, memory score in the 3rd tertile of omega-3 was higher than in the 1st tertile (p = 0.01). See Table 2. Columns show mean scores and error bars indicate SEM.
Fig.2
Fig.2
Global cognition after 2 years according to baseline omega-3 fatty acid concentration. The interaction between omega-3 tertiles and B vitamin treatment was significant (p = 0.09). In the B vitamin group, global cognition score in the 3rd tertile of omega-3 was higher than in 1st tertile (p = 0.035). See Table 2. Columns show mean scores and error bars indicate SEM.
Fig.3
Fig.3
(A) Clinical Dementia Rating score after 2 years according to baseline omega-3 fatty acid concentration. The interaction between omega-3 tertiles and B vitamin treatment did not reach significance (p = 0.13). In the 3rd tertile of combined omega-3 fatty acids, the percent of subjects with CDR >0 was lower in the B vitamin group than in the placebo group (p = 0.043). See Table 2. Columns show mean scores and error bars indicate SEM. (B) Clinical Dementia Rating sum of boxes score after 2 years according to baseline omega-3 fatty acid concentration. The interaction between omega-3 tertiles and B vitamin treatment was not significant (p = 0.35). In the 3rd tertile of combined omega-3 fatty acids, the CDRsob score was lower in the B vitamin group than in the placebo group (p = 0.040). See Table 2. Columns show mean scores and error bars indicate SEM.
Fig.4
Fig.4
Longitudinal scores of episodic memory (HVLT-DR) across tertiles of combined omega-3 fatty acids. Solid line: B vitamin group; dashed line: placebo group. Ranges of the tertiles are given in Supplementary Table 4. The likelihood ratio test for interaction between B vitamin treatment and combined omega-3 tertiles was significant at an alpha level 10% (p = 0.086, Supplementary Table 6). In the 3rd tertile of combined omega-3, the average HVLT-DR significantly increased in the B vitamin group by 0.46 points per year of follow-up (p = 0.013) compared to no significant change in the placebo group (Supplementary Table 6). Error bars represent SEM.
Fig.5
Fig.5
Metabolic interactions in the homocysteine methylation cycle with omega-3 fatty acids. Hcy, homocysteine; PEMT, phosphatidylethanolamine N-methyl transferase; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; THF, tetrahydrofolate.

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