Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer's disease

Eur J Nutr. 2022 Mar;61(2):589-604. doi: 10.1007/s00394-021-02655-4. Epub 2021 Aug 15.

Abstract

Purpose: There is an ever-growing body of literature examining the relationship between dietary omega-3 polyunsaturated fatty acids (ω3 PUFAs) and cerebral structure and function throughout life. In light of this, the use of ω3 PUFAs, namely, long-chain (LC) ω3 PUFAs (i.e., eicosapentaenoic acid and docosahexaenoic acid), as a therapeutic strategy to mitigate cognitive impairment, and progression to Alzheimer's disease is an attractive prospect. This review aims to summarise evidence reported by observational studies and clinical trials that investigated the role of LC ω3 PUFAs against cognition impairment and future risk of Alzheimer's disease.

Methods: Studies were identified in PubMed and Scopus using the search terms "omega-3 fatty acids", "Alzheimer's disease" and "cognition", along with common variants. Inclusion criteria included observational or randomised controlled trials (RCTs) with all participants aged ≥ 50 years that reported on the association between LC ω3 PUFAs and cognitive function or biological markers indicative of cognitive function linked to Alzheimer's disease.

Results: Evidence from 33 studies suggests that dietary and supplemental LC ω3 PUFAs have a protective effect against cognitive impairment. Synaptic plasticity, neuronal membrane fluidity, neuroinflammation, and changes in expression of genes linked to cognitive decline have been identified as potential targets of LC ω3 PUFAs. The protective effects LC ω3 PUFAs on cognitive function and reduced risk of Alzheimer's disease were supported by both observational studies and RCTs, with RCTs suggesting a more pronounced effect in individuals with early and mild cognitive impairment.

Conclusion: The findings of this review suggest that individuals consuming higher amounts of LC ω3 PUFAs are less likely to develop cognitive impairment and that, as a preventative strategy against Alzheimer's disease, it is most effective when dietary LC ω3 PUFAs are consumed prior to or in the early stages of cognitive decline.

Keywords: Alzheimer’s disease; Cognitive impairment; Docosahexaenoic acid; Eicosapentaenoic acid; Neurodegeneration; Polyunsaturated fatty acids.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / prevention & control
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / prevention & control
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Middle Aged

Substances

  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid