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

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.

Cyclooxygenases as Potential PET Imaging Biomarkers to Explore Neuroinflammation in Dementia.

The most frequently studied target of neuroinflammation using PET is 18-kDa translocator protein, but its limitations have spurred the molecular imaging community to find more promising targets. This article reviews the development of PET radioligands for cyclooxygenase (COX) subtypes 1 and 2, enzymes that catalyze the production of inflammatory prostanoids in the periphery and brain. Although both isozymes produce the same precursor compound, prostaglandin H2, they have distinct functions based on their differential cellular localization in the periphery and brain. For example, COX-1 is located primarily in microglia, a resident inflammatory cell in the brain whose role in producing inflammatory cytokines is well documented. In contrast, COX-2 is located primarily in neurons and can be markedly upregulated by inflammatory and excitatory stimuli, but its functions are poorly understood. This article reviews these 2 isozymes as biomarkers of neuroinflammation, as well as the radioligands that have recently been developed to image them in animals and humans. To place this work into context, the properties of COX-1 and COX-2 are compared with 18-kDa translocator protein, with special consideration of their application in Alzheimer disease as a representative neurodegenerative disorder.