Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment

J Nutr Health Aging. 2016 Feb;20(2):161-9. doi: 10.1007/s12603-015-0609-6.


Objectives: To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment.

Design: Randomized, double-blind, placebo-controlled study.

Setting: Academic medical center.

Participants: Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia.

Intervention: Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks.

Measurements: Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI).

Results: At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition.

Conclusion: Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

Trial registration: NCT01746303.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Animals
  • Dietary Supplements*
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / pharmacology
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Eicosapentaenoic Acid / metabolism
  • Eicosapentaenoic Acid / pharmacology
  • Eicosapentaenoic Acid / therapeutic use*
  • Erythrocyte Membrane / drug effects
  • Erythrocyte Membrane / metabolism
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Female
  • Fish Oils / metabolism
  • Fish Oils / pharmacology
  • Fish Oils / therapeutic use*
  • Gyrus Cinguli / drug effects*
  • Humans
  • Male
  • Memory Disorders / blood
  • Memory Disorders / drug therapy*
  • Memory, Short-Term / drug effects*
  • Middle Aged
  • Oxygen / blood


  • Fish Oils
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Oxygen

Associated data