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?

Abstract

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. Secondary exploratory analysis of the randomized controlled MAPT prevention trial. 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. 800mg docosahexaenoic acid (DHA) and 225mg eicosapentaenoic acid (EPA) daily versus placebo. Erythrocyte omega-3 index was measured at baseline. Cognition was measured over 3 years with a composite cognitive score (mean of 4 z-scores). 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%. 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.