Table 3. Summary of Results from Relevant Observational Studies Regarding DHA/EPA Status and Memory Outcomes.
| Study | Memory Outcome (Test) | Observation | Conclusion |
|---|---|---|---|
| Beydoun, 2007 [30] | Recent Memory (DWRT) a | No effect was observed on delayed word recall among any of the subgroups considered. | “Promoting higher intakes of n-3 HUFAs b in the diet of hypertensive and dyslipidemic persons may have substantial benefits in reducing their risk of cognitive decline in the area of verbal fluency. However, clinical trials are needed to confirm this finding.” |
| de Groot, 2007 [31] | Memory (Visual Verbal Word Learning Tasks) | WLTtot c (# words)*and WLTdr d (# words) were significantly different between baseline and 22 weeks (P<0.05). Performances on WLTtot (P = 0.002), WLTdr (P = 0.014) were significantly better at 22 week. | “In conclusion, this study provides a preliminary indication that a higher DHA e status might be associated with slower learning curves. However, additional studies are necessary.” |
| Dullemeijer, 2007 [32] | Memory Z-Score (Immediate & delayed recall) | “Participants improved on memory over 3y; the mean (± SD) 3-year change in z scores was 0.34 ± 0.73 for memory, because of procedural learning effects.” | In older Dutch adults, higher plasma n-3 PUFA were not associated with less decline in 3-year word fluency |
| Kalmijn, 2004 [33] | Memory Function Z-Scores (Total, maximal, & delayed recall scores for Verbal Learning Test were averaged.) | Adjusted OR* for risk of impaired memory function (lowest 10%) according to one SD increase in fatty fish or fatty acid intake. EPA + DHA 1.01 (0.85–1.20) Fatty Fish 0.95 (0.80–1.13) *OR h (95% CI) adjusted for age, sex, education, alcohol, smoking, & total energy intake | “Fatty fish and marine omega-3 PUFA i consumption was associated with a reduced risk … of impaired cognitive function in this middle-aged population.” |
| Kesse-Guyot, 2011 [34] | Memory Test (5-word test of immediate & delayed verbal memory including free & cued recall | No significant association between poor scores on the MMSE l and 5-word cognitive tests and intake of fish and related fatty acids.” | “Cognitive complaints, which may be an early indicator of cognitive decline, are less frequent among the elderly who have a high long-chain n-3 acids intake, as assessed 13 years earlier.” |
| Milte, 2011 [35] | Immediate Memory (RAVLT) p | Higher levels of the n-6 PUFAs DGLA, AA, DPA and lower levels of the n-3 PUFAs EPA and DPA were associated with poorer performance on various cognitive assessments and self- reported scales. In addition, lower levels of various n-3 PUFAs were associated with higher levels of n-6 PUFAs, including n-6 DPA.” | “Despite limitations, this study adds to the growing evidence of a possible role of PUFAs in memory problems and mood in the elderly. It points to differences in n-3 and n-6 PUFA status in adults with MCI compared with healthy controls. It also provides evidence of associations between higher n-6 DPA status and poorer cognition, memory and perception of health, which are modulated by depressive symptoms. It suggests that modification of PUFA intakes may positively affect mood and memory in adults with MCI….” |
| Muldoon, 2010 [36] | General / Episodic Memory & Working Memory (WMS-3) q | Higher DHA blood levels were associated with better scores on tests of working memory. In contrast, EPA was marginally associated (P = 0.054) only with working memory. | “The findings in this report suggest that DHA may be the (n-3) fatty acid most closely related to cognitive function.” |
| Phillips, 2012 [37] | Composite Memory Score | “In this model* plasma PC EPA and DHA, and dietary omega-3 intake score were all positive predictors of the composite memory performance score.” *Controlling for age, years of education, IMDs, and sex. | ”These results are consistent with the possibility that omega-3 fatty acid nutrition has an impact on cognitive decline, but could equally be explained by dietary changes that occurred after onset of cognitive decline. It is also possible that the results could be explained by unknown confounding factors.” |
| Samieri, 2011 [38] | Working Memory (BVRT) t | A significant interaction was found between plasma DHA proportion and the ApoE-ε4 u on the change of BVRT scores over time (p = 0.02). A 1-SD increase in plasma DHA was not associated with the evolution of BVRT performances over time in ApoE-ε4 non-carriers, but strongly related to slower decline on BVRT performances in ApoE-ε4 carriers (β = 0.061 (SD = 0.024, p = .01). | “Plasma DHA was associated with slower decline on BVRT performances in ApoE- ε 4 carriers only. EPA and DHA may contribute to delaying decline in visual working memory in ApoE- ε 4 carriers. In older depressed subjects, EPA, but not DHA, may slow cognitive decline.” |
| Tan 2012 [39] | Verbal Memory (LM-d) v ; Visual Memory (VR-d w ) | RBC x DHA levels showed a continuous positive association with performance in tests of visual memory (VR-d). There was no statistically significant relationship between RBC DHA and performance on verbal memory (LM-d). | “Lower RBC DHA levels are associated with smaller brain volumes and a ‘vascular’ pattern of cognitive impairment even in persons free of clinical dementia.” |
| Titova, 2013 [40] | Declarative Memory—7 minute screening (ECR) y | The dietary intake of EPA and DHA was positively linked to the 7MSz score (i.e., the total score obtained on 4 cognitive subtests, 1 of which was the ECR). This association remained significant in all models. However, there were no associations between plasma EPA or DHA with the performance on the 7MS estimates. | “Study results provide a potential link between diets rich in EPA & DHA & enhanced mental health in the elderly.” |
| Whalley, 2004 [41] | Immediate Memory (AVLT) aa | Pearson’s correlation coefficients between AVLT scores and log-transformed RBC LCPUFAs bb content was not statistically significant. | Total RBC n-3 FA & ratio of DHA to AA was associated with better cognitive function in late life before and after adjustment for childhood IQ.”If associations with n-3 content are causal, optimization of n-3 and n-6 fatty acid intakes could improve retention of cognitive function in old age.” |
| Whalley, 2008 [42] | Immediate Memory (AVLT) | DHA was associated with significantly (P <0.001) higher scores on AVLT. DHA also had a differential effect over time (P <0.001): AVLT was significantly (P <0.001) lower at wave 1 and wave 2 than at wave 3. | Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE ε4 allele. “These data are evidence of a gene X environment interaction for cognitive aging. They are relevant to the analysis of trials of n-3 PUFA supplements in cognitive aging and dementia prevention….” |
aDWRT = Delayed Word Recall Test;
b HUFAs = highly unsaturated fatty acids;
c WLTtot = Word Learning Task total;
d WLTdr = Word Learning Tasks delayed recall;
e DHA = Docosahexaenoic Acid;
f SD = Standard Deviation;
g EPA = Eicosapentaenoic Acid;
h OR = Odds Ratio
i PUFA = Polyunsaturated Fatty Acids;
jBMI = body mass index;
k CES-D = Center for Epidemiologic Studies Depression Scale (CES-D);
l MMSE = Mini-Mental State Examination;
m MCI = mild cognitive impairment;
nDGLA = digamma linoleic acid;
o; AA—Arachidonic Acid;
p RAVLT = Rey Auditory Verbal Learning Test;
q WMS-3 = Wechsler Memory Scale, 3rd ed.;
r PC = Phosphatidylcholine;
s IMD = Index of Multiple Deprivation;
t BVRT = Benton Visual Retention Test;
u APOE ε4 = Apolipoprotein E Allele 4;
v LM-d = Logical Memory test—delayed;
w VR-d = Visual Reproduction test delayed recall;
x RBC = Red Blood Cell;
y ECR = Enhanced Cued Recall;
x7MS = 7-Minute Scoring of the ECR;
aa AVLT = Rey Auditory Verbal Learning Test;
bb LCPUFA = Long-chain Polyunsaturated Fatty Acids;