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. 2024 Nov;20(11):8062-8073.
doi: 10.1002/alz.14304. Epub 2024 Oct 11.

APOE ε4 carrier status moderates the effect of lifestyle factors on cognitive reserve

Deirdre M O'Shea  1 , Andrea S Zhang  2 , Katana Rader  1 , Rebecca L Shakour  2 , Lilah Besser  1 , James E Galvin  1
Affiliations

APOE ε4 carrier status moderates the effect of lifestyle factors on cognitive reserve

Deirdre M O'Shea et al. Alzheimers Dement. 2024 Nov.

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) ε4 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 ε4 status and mindfulness and social engagement on cognitive reserve, indicating stronger associations for APOE ε4 carriers.

Discussion: APOE ε4 carriers may benefit more from certain lifestyle factors, potentially through stress reduction and anti-inflammatory pathways. These findings support integrating APOE ε4 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 ε4 carriers. Study uses residual scores from Cognivue Clarity tests to estimate cognitive reserve. APOE ε4 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.

Keywords: APOE ε4 status; Alzheimer's disease; cognitive function; cognitive reserve; lifestyle factors.

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Conflict of interest statement

The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Conceptual SEM models for main and interaction effects of lifestyle factors on cognitive reserve. APOE, apolipoprotein E; MIND, Mediterranean‐DASH Intervention for Neurodegenerative Delay; SEM, structural equation model.
FIGURE 2
FIGURE 2
Interaction effects of APOE ε4 status and lifestyle factors on cognitive reserve. (A) Interaction between social engagement and APOE ε4 status on cognitive reserve, indicating a significant positive effect in APOE ε4 carriers. (B) Interaction between applied mindfulness and APOE ε4 status, showing a significant positive effect in APOE ε4 carriers. AMPS, Applied Mindfulness Process Scale; APOE, apolipoprotein E.
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