The association between omega-3 polyunsaturated fatty acid intake and reduced risk of Alzheimer's disease

By Pooja Toshniwal PahariaReviewed by Lily Ramsey, LLMApr 7 2023

In a recent study published in The American Journal of Clinical Nutrition, researchers evaluated the association between omega-3 polyunsaturated fatty acids intake, cognitive decay, and dementia.

Study: The relationship of omega-3 fatty acids with dementia and cognitive decline: evidence from perspective cohort studies of supplementation, dietary intake, and blood markers. Image Credit: SewCreamStudio/Shutterstock.com

Background

Alzheimer's disease (AD), a neurodegenerative disorder, is highly prevalent among the elderly and lacks effective therapeutics, warranting the identification of risk factors that can be modified to prevent and/or delay AD onset.

Omega-3, obtained primarily via dietary sources such as fish and plants, improves brain development and cognition and reduces inflammation.

However, observational-type studies reported unclear findings concerning omega-3 supplement efficacy in preventing AD, cognitive decay, and dementia.

Moreover, randomized controlled trials (RCTs) have reported the limited protection conferred by omega-3 fatty acids against AD and cognitive impairments. Further, studies assessing the interactions between apolipoprotein E (APOE ε4) and omega-3 have reported contradictory findings.

About the study

The present study investigated whether omega-3 intake prevented AD, cognitive decline, or dementia.

Longitudinal data of 1,135 AD Neuroimaging Initiative (ADNI) study non-demented participants, aged 55 to 90 years, were analyzed to determine the relationship between omega-3 intake and serological biomarkers with new-onset AD over six years of follow-up.

Further, the team performed a systematic review and meta-analysis of previously published cohort-type studies to verify the associations between dietary omega-3 fatty acid intake and biomarkers and cognitive decay or dementia.

Further, meta-regression modeling was performed to assess the dose-response relationships, adjusting for covariates such as age, sex, level of education, APOE ε4 status, and cognitive status to determine the relative risk (RR) values.

Face-to-face interviews were conducted to obtain data on the history of medical disorders, and individuals underwent neuropsychological and cognitive evaluation at study initiation and follow-up.

Dietary supplementation data were obtained using medication-taking questionnaires. Individuals taking omega-3 supplements over more than 1.0 years comprised the 'exposed' group, and the others comprised the 'non-exposed' group.

Blood samples were obtained from all participants. The team quantified the composition of fatty acids using Nightingale Health's nuclear magnetic resonance (NMR) metabolomics and serological metabolites using NMR spectroscopy.

AD diagnosis was based on the national institute of Neurological and Communicative Disorders and Stroke and the AD and Related Disorders Association (NINCDS-ADRDA) criteria. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, fourth/ fifth edition (DSM-IV/ DSM-V). Cognitive decay was evaluated using the mini-mental state examination scale.

The Cochrane Library, PubMed, and EMBASE databases were searched, without language restrictions, until March 17 2022, for case-control-type or cohort-type original research studies evaluating the associations between omega-3 intake and its biomarkers, and new-onset AD, cognitive decay, or any-cause dementia.

Data were extracted by two independent researchers, and discrepancies were resolved by a third researcher. Study quality was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). Cox proportional hazards-type modeling was performed to calculate the hazard ratios (HR).

Results

Among ADNI study participants, 46% were female, and the mean duration of follow-up was 2.8 years. Individuals developing AD showed apolipoprotein E-carrying tendency. Long-term omega-3 consumers showed a 64.0% reduction in AD risk (HR 0.4).

Moderate-high levels of evidence indicated that dietary omega-3 intake could prevent cognitive decay or any-cause dementia by 20.0%, particularly for docosahexaenoic acid (DHA) intake (RR 0.8), adjusting for apolipoprotein E status (RR 0.8).

The dose-response analysis, comprising 27,161 and 3,797 individuals and cases, respectively, showed that every 0.10 g/day increment of eicosapentaenoic acid (EPA) and DHA intake reduced cognitive decay risk by 10% and 8.0%, respectively.

Moderate-high level evidence was obtained for lower cognitive decay risks among individuals with elevated serological EPA levels (RR 0.9) and erythrocyte membrane DHA (RR 0.9).

Initially, 18,230 records were identified after reviewing the titles and abstracts, of which 709 records were considered, and after detailed evaluation, 48 studies were eligible for the analysis, 31 of which were considered for the meta-analysis, comprising 103,651 individuals.

This was then reduced to a meta-analysis of 18 studies comprising 46,548 individuals, which showed that omega-3 intake significantly lowered the risk of cognitive decay (RR 0.9), especially after adjusting for apolipoprotein E status (RR 0.8).

Dietary DHA intake reduced the risk of dementia and AD by 27% and 24%, respectively. The risk of cognitive decay among older individuals aged 65.0 years and above was reduced significantly by 23.0%.

The credibility of evidence was the highest for erythrocytes, lower for diet, and least for plasma. Sensitivity analysis, excluding cases diagnosed within one year, yielded similar results.

Conclusions

Overall, the study findings showed that omega-3 polyunsaturated fatty acid use significantly lowered the risk of AD, with probable moderating effects by apolipoprotein E, in a dose-dependent manner, especially among long-term consumers.

The meta-analysis results strengthened the relationship between omega-3 and their peripheral biomarker levels and dementia, cognitive decay, or AD.

The authors proposed that one gram daily could be considered the threshold dose for omega-3 intake to prevent cognitive decay.

Serological DHA and EPA levels, and erythrocyte DHA levels, must be examined regularly among individuals at an elevated risk of AD. However, future studies must be conducted to improve understanding of the gene-environment interactions in omega-3 intake.