Nutrition and the ageing brain: Moving towards clinical applications
Emma Flanagan Ageing Research Reviews Volume 62, September 2020,
Omega-3 fatty acids have received considerable attention in the context of nutrition and ageing particularly regarding their possible role in reducing the risk of age-related cognitive decline. Indeed, observational studies such as the Three City Study showed that higher blood levels of the long-chain omega-3 fatty acid eicosapentaenoic acid (EPA) were associated with lower dementia risk and less atrophy of the medial temporal lobe (Samieri et al., 2008, 2012) (whereas blood levels of docosahexaenoic acid (DHA) did not reach a significant association with dementia outcomes in these studies). However, with regards to pathological age-related decline specifically, there have been findings of higher blood levels of DHA to be associated with lower dementia risk (Zhang et al., 2016). A meta-analysis showed that observational studies support a favourable association between intake/blood levels of DHA (alone or combined with EPA) with memory function in older adults with mild memory complaints (Yurko-Mauro et al., 2015).
But randomised-controlled trials (RCT) failed so far to show positive effects of omega-3 fatty acids supplementation on cognitive performance in cognitively healthy older subjects (van de Rest et al., 2008), or on cognitive decline in elderly people with memory complaints (Multidomain Alzheimer Preventive Trial (MAPT) (Andrieu et al., 2017)). The DHA dose used in the MAPT (800 mg/day) is below the maximum recommended daily intake and even higher doses (above 1 g) showed negative results on cognitive outcomes in trials for MCI and mild AD probably because the brain pathology is already well advanced in those patients (Yassine and Schneider, 2017). Therefore omega-3 supplementation might better be tested for prevention purposes in patients with early dementia (prodromal stages) in trials with larger sample size and for longer periods to ensure that the intervention has a chance for success. Indeed, findings from a previous meta-analysis have hinted that the positive effects of omega-3 supplementation on cognitive performance could be limited to specific cognitive domains in milder cognitive impairment in the absence of dementia (Mazereeuw et al., 2012).
Such inconsistency in findings could in part be due to the challenges relating to measuring habitual intake based on biomarkers of nutrients not consumed on a daily basis (i.e. marine long-chain omega-3 fatty acids) using a single blood draw; and in part to factors such as large variability in composition of bioactives within the same type of food source; and individual differences in rates of nutrient metabolism. Another possible reason for inconsistency is that omega-3 fatty acids may need to interact with other nutrients in order to have a beneficial effect; for example, there is evidence of interaction with B vitamins.