Defining the Optimal Target Population for Trials of Polyunsaturated Fatty Acid Supplementation Using the Erythrocyte Omega-3 Index: A Step Towards Personalized Prevention of Cognitive Decline?

Objectives: to identify the optimal erythrocyte omega-3 index cut-off for predicting cognitive decline and/or polyunsaturated fatty acid (PUFA) treatment response, in order to better define the target population for future dementia prevention trials.

Design And Setting: Secondary exploratory analysis of the randomized controlled MAPT prevention trial.

Participants: 724 dementia-free subjects aged 70 or older with subjective memory complaints, limitations in one instrumental activity of daily living, and/or slow gait speed.

Intervention: 800mg docosahexaenoic acid (DHA) and 225mg eicosapentaenoic acid (EPA) daily versus placebo.

Measurements: Erythrocyte omega-3 index was measured at baseline. Cognition was measured over 3 years with a composite cognitive score (mean of 4 z-scores).

Results: Placebo group subjects in the lowest quartile of baseline erythrocyte omega-3 index (i.e. ≤4.83%) underwent significantly more 3-year cognitive decline than the other quartiles (mean composite score difference 0.14, 95%CI [0.00, 0.28], p=0.048). In a ROC curve analysis, the optimal omega-3 index cut-off for predicting notable cognitive decline was 5.3%. There was a consistent but non-significant difference in 3-year cognitive decline of approximately 0.12 points between PUFA-treated and placebo subjects with "low" baseline omega-3 index when the cut-off was set at ≤5.27%.

Conclusions: Dementia-free older adults with an omega-3 index below approximately 5% are at increased risk of cognitive decline, and could be a good target population for testing the cognitive effects of PUFA supplementation.