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?

J Nutr Health Aging. 2018;22(8):982-998. doi: 10.1007/s12603-018-1052-2.

Abstract

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.

Keywords: Cognition; omega-3; prevention; tailored therapy; trial design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged
  • Cognition / physiology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / prevention & control*
  • Dementia / physiopathology
  • Dietary Supplements
  • Docosahexaenoic Acids / therapeutic use*
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / therapeutic use
  • Erythrocytes / chemistry
  • Fatty Acids, Omega-3 / analysis*
  • Female
  • Humans
  • Male
  • Memory
  • Placebos / administration & dosage
  • Retrospective Studies
  • Walking Speed / physiology

Substances

  • Fatty Acids, Omega-3
  • Placebos
  • Docosahexaenoic Acids
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid