Abstract
Abstract INTRODUCTION This study examines the role of lifestyle factors in cognitive reserve among older adults, focusing on the moderating effect of apolipoprotein E ( APOE ) ε 4 status. METHODS Data from 157 participants aged 45 and older from the Healthy Brain Initiative (HBI) were analyzed. Cognitive reserve was estimated using residual scores from Cognivue Clarity tests after accounting for brain atrophy and white matter hyperintensities (WMHs). Lifestyle factors included education, occupational attainment, physical activity, social engagement, diet, and mindfulness. Structural equation models were conducted to assess interactions. RESULTS Significant interactions were found between APOE ε 4 status and mindfulness and social engagement on cognitive reserve, indicating stronger associations for APOE ε 4 carriers. DISCUSSION APOE ε 4 carriers may benefit more from certain lifestyle factors, potentially through stress reduction and anti‐inflammatory pathways. These findings support integrating APOE ε 4 genetic screening into personalized prevention strategies to enhance interventions aimed at preserving cognitive function and delaying dementia onset in at‐risk populations. Highlights Mindfulness and social engagement have increased cognitive reserve in APOE ε 4 carriers. Study uses residual scores from Cognivue Clarity tests to estimate cognitive reserve. APOE ε 4 carriers show stronger associations with certain lifestyle factors on cognitive reserve. Personalized interventions could enhance cognitive resilience in genetically at‐risk populations. Comprehensive assessment of multiple lifestyle factors highlights targeted intervention benefits.