Interaction betweenAPOE4status and lifestyle on brain and cognitive outcomes in cognitively unimpaired older adults

Abstract

AbstractINTRODUCTIONAPOE4genotype and lifestyle have been associated with Alzheimer’s disease (AD) risk, but how they interact on neuroimaging and cognitive markers of aging and AD remains unclear.METHODSIn 135 cognitively unimpaired older adults from the baseline Age-Well trial, we investigated the interaction betweenAPOE4 status and cognitive activity, diet and physical activity on cognition and neuroimaging markers of neurodegeneration and amyloid.RESULTSHigher cognitive activity correlated with lower medial temporal lobe (MTL) volume and perfusion inAPOE4-carriers, but increased cognitive performance irrespective ofAPOE4status. Higher adherence to the Mediterranean diet correlated with higher MTL metabolism and attention scores inAPOE4-carriers. Conversely, physical activity correlated with higher MTL perfusion and lower amyloid inAPOE4-non-carriers only.DISCUSSIONGenetics and lifestyle factors act through different mechanisms to helpAPOE4-carriers resist or cope with brain alterations and postpone cognitive decline. Our results support the need of personalized lifestyle-based interventions for AD.Trial Registration InformationEudraCT: 2016-002441-36; IDRCB: 2016-A01767-44;ClinicalTrials.govIdentifier:NCT02977819.