Some, but not all, observational studies suggest that diets high in LC omega-3s are associated with a reduced risk of cognitive decline, Alzheimer’s disease, and dementia [144,145]. Because DHA is an essential component of cellular membrane phospholipids in the brain, researchers hypothesize that LC omega-3s might protect cognitive function by helping to maintain neuronal function and cell membrane integrity within the brain [145]. This hypothesis is supported by findings from case-control studies indicating that patients with Alzheimer’s disease have lower serum levels of DHA than cognitively healthy people [146,147]. Lower serum DHA levels are also associated with more cerebral amyloidosis (build-up of protein deposits called amyloids) in healthy older adults, whereas higher DHA is correlated with preservation of brain volume [148].

Several observational studies have examined the effects of fish, EPA, and/or DHA intakes on cognitive function in healthy older adults. In a prospective cohort study involving 210 healthy men age 70–89, fish consumption was associated with less cognitive decline at follow-up 5 years later [149]. In addition, a dose-response relationship was observed between tertiles of dietary EPA plus DHA intake and subsequent 5-year cognitive decline. Similarly, in the Rotterdam Study, a population-based prospective study of people age 55 or older who were free from dementia at baseline, higher fish consumption among 5,386 study participants was associated with a 60% lower risk of dementia and a 70% lower risk of Alzheimer’s disease over an average of 2.1 years [150]. Subsequent follow-up 6 years after baseline, however, found no associations between omega-3 intakes and incidence of dementia or Alzheimer’s disease [151]. The authors suggest that the discrepancy might be explained by the short follow-up period in the first analysis and the small number of patients who developed dementia. A higher omega-3 index was associated with a greater hippocampal volume in the Women’s Health Initiative Memory Study [152] and with a larger brain volume and improved cognitive test scores in the Framingham Offspring cohort [153]. A 2016 dose-response meta-analysis of 21 cohort studies found that increased intakes of fish and dietary DHA were both inversely associated with the risks of dementia and Alzheimer’s disease [154]. Specifically, a 100 mg/day incremental increase in DHA intake was associated with a 14% lower risk of dementia and a 37% lower risk of Alzheimer’s disease.

Results from clinical trials, however, suggest that LC omega-3 supplementation does not affect cognitive function in older adults who have no cognitive impairment. In a trial in the United Kingdom, 748 cognitively healthy adults age 70–79 years received either 500 mg DHA and 200 mg EPA or placebo daily for 24 months [155]. Cognitive function did not differ significantly between the two groups, although cognitive function did not decline in either group. In the Age-Related Eye Disease Study 2 (AREDS2) clinical trial, treatment with 350 mg DHA and 650 mg EPA for 5 years did not have a significant effect on cognitive function in 3,501 older adults (mean age 72.7 years) with age-related macular degeneration (AMD) [146].

Clinical trial results also suggest that LC omega-3 supplementation does not benefit patients with Alzheimer’s disease, although it might help patients with mild cognitive impairment. For example, daily supplementation with 2 g DHA for 18 months did not slow the rate of cognitive decline compared to placebo in 295 participants (mean age 76 years) with mild to moderate Alzheimer’s disease [156]. In the OmegaAD trial, daily supplementation with 1,700 mg DHA and 600 mg EPA for 6 months in 174 older adults with mild to moderate Alzheimer’s disease also failed to slow down the rate of cognitive decline compared to placebo [157]. However, a subgroup of patients with very mild impairment experienced a significant reduction in the rate of cognitive decline. In a small trial in Malaysia, fish oil supplementation (1,290 mg DHA and 450 mg EPA daily) for 12 months improved memory—particularly short-term, working, and verbal memory—and delayed recall compared to placebo in 35 older adults with mild cognitive impairment [158].

Several systematic reviews and meta-analyses have assessed the effects of omega-3 supplementation on cognitive function and dementia in healthy older adults and those with Alzheimer’s disease or cognitive impairment [144,159-161]. Overall, the findings indicate that LC omega-3 supplementation does not affect cognitive function in healthy older adults or in people with Alzheimer’s disease compared to placebo. For people with mild cognitive impairment, omega-3s may improve certain aspects of cognitive function, including attention, processing speed, and immediate recall [161]. However, these findings need to be confirmed in additional clinical trials.