The Cognitive Ageing, Nutrition and Neurogenesis trial: Design and progress

Introduction: Cohort studies indicate that long-chain n-3 polyunsaturated fatty acids and flavonoids may improve cognition and reduce dementia risk. The neuroprotective effects of these dietary components indicate that they are likely to be additive and potentially synergistic. Methods: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that an intervention comprising long-chain n-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and cocoa flavan-3-ols (n-3 FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults with mild cognitive impairment or subjective memory impairment. A double-blinded, placebo-controlled parallel design is used. Two hundred fifty-nine adults (aged ≥55 years) with mild cognitive impairment or subjective memory impairment were recruited and randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognitive performance was measured three times over the 1-year intervention, at 0 (baseline), 3, and 12 months. The primary end point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora speciation and metabolism, red blood cell fatty acid status, and urine flavan-3-ol metabolites. The intervention arms were matched for sex and apolipoprotein E4 status to allow retrospective exploratory analysis of the impact of these variables on response to intervention. Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018. Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia