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

Abstract INTRODUCTION APOE4 genotype 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. METHODS In 135 cognitively unimpaired older adults from the baseline Age-Well trial, we investigated the interaction between APOE 4 status and cognitive activity, diet and physical activity on cognition and neuroimaging markers of neurodegeneration and amyloid. RESULTS Higher cognitive activity correlated with lower medial temporal lobe (MTL) volume and perfusion in APOE4 -carriers, but increased cognitive performance irrespective of APOE4 status. Higher adherence to the Mediterranean diet correlated with higher MTL metabolism and attention scores in APOE4- carriers. Conversely, physical activity correlated with higher MTL perfusion and lower amyloid in APOE4 -non-carriers only. DISCUSSION Genetics and lifestyle factors act through different mechanisms to help APOE4 -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 Information EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819 .