“Omega-3 fatty acids are nootropic agents that are beneficial for brain development, anti-inflammation, and cognitive preservation,” the team of Chinese researchers from Qingdoa University wrote in The American Journal of Clinical Nutrition. “DHA is an essential fatty acid that maintains brain function and integrity, and its derivatives can modulate glial cell activity and improve cognition in the early stages of Alzheimer’s disease (AD).”
The study drew data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort and conducted an additional meta-analysis of published cohort studies to evaluate the longitudinal relationships of omega-3 intake and its biomarkers with all-cause dementia or cognitive decline; as well as a causal dose–response analysis.
Omega-3s and the brain
In the search to protect the aging brain in the ever-increasing older population, omega-3 intake and blood concentrations have emerged as potential modifiable risk factors.
A large cohort review published last year linked low red blood cell docosahexaenoic acid (DHA) levels with smaller brain volume and a vascular pattern of cognitive impairment. It also suggested that starting interventions as early as midlife, as well as maintaining an optimal Omega-3 Index (8% or higher), could play an important role in staving off cognitive decline.
In the current review, the Chinese research team pointed to several mechanisms that might explain the importance of omega-3 intake and its biomarkers including inhibition of tau phosphorylation for neuroprotection and brain neuron integrity; targeting of AD-specific pathology pathways in apolipoprotein E4 (APOE ε4) allele carriers; and balancing inflammation and immune function associated with AD pathogenesis.
APOE ε4 is the strongest genetic risk factor for AD, which is attributed to the gene’s role in disrupting lipid metabolism and stress regulation. About 15% to 25% of people have this allele, and 2% to 5% carry two copies, according the National Institute on Aging.
The study gathered longitudinal data from 1,135 participants without dementia (between the ages of 55 and 90) in the ADNI cohort to assess the associations of omega-3 intake and blood biomarkers with incident AD, dementia, or cognitive decline during the six-year follow-up.
The supplemental meta-analysis of published cohort studies (including 27 new cohorts compared to previous studies) provided what the review describes as “the most comprehensive evidence of the relationship of omega-3 fatty acids and dementia”.
“In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD,” they reported. “After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by around 20%, especially for docosahexaenoic acid (DHA) intake and for studies that were adjusted for apolipoprotein APOE ε4 status.”
The findings also showed that each 0.1 g/d increment of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8% ~ 9.9% lower risk of cognitive decline, supporting the hypothesis that efficacy of omega-3 supplementation is dose-dependent.
“Although we did not observe a significant linear relationship between dietary omega-3 fatty acid intake and risk of cognitive decline, risk of cognitive decline decreased when the intake of omega-3 fatty acids exceeded 1.0 g/d,” the researchers wrote. “For this reason, we propose that 1.0 g/d may be the threshold dosage of omega-3 fatty acids for the prevention of cognitive decline.”
The review called for further study into the gene–environment interactions involved in omega-3 intake. It also suggested that future cohort studies be refined to include baseline omega-3 measures with daily intake dosage and more detailed supplement information; genetic factors (e.g., APOE ε4 genotype) and objective screening of cognitive level; and consideration of the interaction between omega-3s and other fatty acids for favorable cognitive outcomes.
Source: The American Journal of Clinical Nutrition
“The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Marker”
Authors: Bao-Zhen We et al.