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. 2016 Apr 11;4(4):CD009002.
doi: 10.1002/14651858.CD009002.pub3.

Omega-3 fatty acids for the treatment of dementia

Marion Burckhardt  1 , Max Herke, Tobias Wustmann, Stefan Watzke, Gero Langer, Astrid Fink
Affiliations

Omega-3 fatty acids for the treatment of dementia

Marion Burckhardt et al. Cochrane Database Syst Rev. .

Abstract

Background: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish and plant sources are commonly considered as a promising non-medical alternative to improve brain functions and slow down the progression of dementia. This assumption is mostly based on findings of preclinical studies and epidemiological research. Resulting explanatory models aim at the role omega-3 PUFAs play in the development and integrity of the brain's neurons, their protective antioxidative effect on cell membranes and potential neurochemical mechanisms directly related to Alzheimer-specific pathology. Epidemiological research also found evidence of malnutrition in people with dementia. Considering this and the fact that omega-3 PUFA cannot be synthesised by humans, omega-3 PUFAs might be a promising treatment option for dementia.

Objectives: To assess the efficacy and safety of omega-3 polyunsaturated fatty acid (PUFA) supplementation for the treatment of people with dementia.

Search methods: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 10 December 2015. We contacted manufacturers of omega-3 supplements and scanned reference lists of landmark papers and included articles.

Selection criteria: We included randomised controlled trials (RCTs) in which omega-3 PUFA in the form of supplements or enriched diets were administered to people with Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) or frontotemporal dementia (FTD).

Data collection and analysis: The primary outcome measures of interest were changes in global and specific cognitive functions, functional performance, dementia severity and adverse effects. Two review authors independently selected studies, extracted data and assessed the quality of trials according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We received unpublished data from the trial authors and collected adverse effects information from the published articles. We conducted meta-analyses for available outcome measures at six months.

Main results: We included three comparable randomised, placebo-controlled trials investigating omega-3 PUFA supplements in 632 participants with mild to moderate AD over six, 12 and 18 months. We found no studies investigating other types of dementia. All trials were of high methodological quality. The overall quality of evidence for most of the outcomes was high.There was no evidence of a benefit from omega-3 PUFAs on cognitive function when measured at six months with the Alzheimer's Disease Assessment Scale - Cognitive subscale (standardised mean difference (SMD) -0.02, 95% confidence interval (CI) -0.19 to 0.15; 566 participants; 3 studies; high quality evidence) or Mini-Mental State Examination (mean difference (MD) 0.18, 95% CI -1.05 to 1.41; 202 participants; 2 studies; high quality evidence) or on activities of daily living (SMD -0.02, 95% CI -0.19 to 0.16; 544 participants; 2 studies; high quality evidence). There was also no effect at six months of treatment on severity of dementia measured with the Clinical Dementia Rating - Sum of Boxes (MD -0.00, 95% CI -0.58 to 0.57; 542 participants; 2 studies; high quality evidence) or on quality of life measured with the Quality of Life Alzheimer's Disease scale (MD -0.10, 95% CI -1.28 to 1.08; 322 participants; 1 study; high quality evidence). There was no difference at six months on mental health measured with the Montgomery-Åsberg Depression Rating Scale (MD -0.10, 95% CI -0.74 to 0.54; 178 participants: 1 study; high quality of evidence) or the Neuropsychiatric Inventory (SMD 0.10, 95% CI -0.07 to 0.27; 543 participants; 2 studies; high quality of evidence). One very small study showed a benefit for omega-3 PUFAs in instrumental activities of daily living after 12 months of treatment (MD -3.50, 95% CI -4.30 to -2.70; 22 participants; moderate quality evidence). The included studies did not measure specific cognitive function. The studies did not report adverse events well. Two studies stated that all adverse events were mild and that they did not differ in overall frequency between omega-3 PUFA and placebo groups. Data from one study showed no difference between groups in frequency of any adverse event (risk ratio (RR) 1.02, 95% CI 0.95 to 1.10; 402 participants; 1 study; moderate quality evidence) or any serious adverse event (RR 1.05, 95% CI 0.78 to 1.41; 402 participants; 1 study; high quality evidence) at 18 months of treatment.

Authors' conclusions: We found no convincing evidence for the efficacy of omega-3 PUFA supplements in the treatment of mild to moderate AD. This result was consistent for all outcomes relevant for people with dementia. Adverse effects of omega-3 PUFAs seemed to be low, but based on the evidence synthesised in this review, we cannot make a final statement on tolerability. The effects on other populations remain unclear.

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Conflict of interest statement

None known.

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
2
2
Study flow diagram.
3
3
Forest plot of comparison: Omega‐3 PUFAs versus placebo for mild to moderate Alzheimer's disease. Analysis 1.1 Mini‐Mental State Examination (MMSE; 6 months' follow‐up, PP analysis).
4
4
Forest plot of comparison: Omega‐3 PUFAs versus placebo for mild to moderate Alzheimer's disease. Published and unpublished. Analysis 1.3 Activities of daily living (6 months' follow‐up, PP analysis). ADCS‐ADL: Alzheimer's Disease Cooperative Study ‐ Activities of Daily Living; DAD: Disability Assessment for Dementia.
5
5
Forest plot of comparison: Omega‐3 PUFA versus placebo for mild to moderate Alzheimer's disease. Published and unpublished. Sensitivity analysis 1.15 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog; 6 months' follow‐up, imputed means for missing data. Assumption: values of missing data = values of control group). LOCF: last observation carried forward; PP: per protocol.
6
6
Forest plot of comparison: Omega‐3 versus placebo for mild to moderate Alzheimer's disease. Published and unpublished. Sensitivity analysis 1.19 Mini‐Mental State Examination (MMSE; 6, 12 and 18 months' follow‐up, per protocol (PP) analysis).
1.1
1.1. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 1 Mini‐Mental State Examination (MMSE; 6 months' follow‐up, per protocol (PP) analysis).
1.2
1.2. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 2 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog; 6 months' follow‐up, PP analysis).
1.3
1.3. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 3 Activities of daily living (6 months' follow‐up, PP analysis).
1.4
1.4. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 4 Older Americans Resources and Services ‐ Instrumental Activities of Daily Living (OARS‐IADL) change scores (12 months' follow‐up, PP analysis).
1.5
1.5. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 5 Clinical Dementia Rating ‐ Sum of Boxes (CDR‐SOB; 6 months' follow‐up, PP analysis).
1.6
1.6. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 6 Neuropsychiatric Inventory (NPI; 6 months' follow‐up, PP analysis).
1.7
1.7. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 7 Montgomery‐Åsberg Depression rating scale (MADRS; 6 months' follow‐up, PP analysis).
1.8
1.8. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 8 Adverse events (18 months' follow‐up, intention‐to‐treat (ITT) analysis)).
1.9
1.9. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 9 Any serious adverse events (18 months' follow‐up, ITT analysis).
1.10
1.10. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 10 Quality of Life Alzheimer's Disease scale (QoL‐AD; 6 months' follow‐up, PP analysis, participant rated).
1.11
1.11. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 11 QoL‐AD scale (6 months' follow‐up, PP analysis, informant rated).
1.12
1.12. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 12 QoL‐AD scale (18 months' follow‐up, PP analysis, informant rated).
1.13
1.13. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 13 QoL‐AD scale (18 months' follow‐up, PP analysis, participant rated).
1.14
1.14. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 14 Sensitivity analysis ADAS‐Cog (6 months' follow‐up, imputed means for missing data. Assumption: values of missing data = values of control group).
1.15
1.15. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 15 Sensitivity analysis MMSE (6, 12 and 18 months' follow‐up, PP analysis).
1.16
1.16. Analysis
Comparison 1 Omega‐3 PUFAs versus placebo, Outcome 16 Sensitivity analysis ADAS‐Cog (6 and 18 months' follow‐up).
See this image and copyright information in PMC

Update of

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Carter 2006 {published data only}
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