Entorhinal Cortex Thinning is Related to White Matter Hyperintensity Growth, Memory Decline, and Leisure Activity in Cognitively Healthy Older Adults

Introduction : Cerebral small vessel disease (cSVD) is a growing epidemic that affects brain health and cognition. Therefore, a more profound understanding of the interplay between cSVD, brain atrophy, and cognition in healthy aging is of great importance. In this study, we examined the association between white matter hyperintensities (WMH) volume, number of lacunes, entorhinal cortex (EC) thickness, and declarative memory in cognitively healthy older participants over a seven-year period, controlling for possible confounding factors. Because there is no cure for cSVD to date, the neuroprotective potential of an active lifestyle has been suggested. Supporting evidence, however, is scarce. Therefore, a second objective of this study is to examine the relationship between leisure activities, cSVD, EC thickness, and declarative memory. Methods : We used a longitudinal dataset, which consisted of five measurement time points of structural MRI and psychometric cognitive ability and survey data, collected from a sample of healthy older adults (baseline N = 231, age range: 64 – 87 years, age M = 70.8 years), to investigate associations between cSVD MRI markers, EC thickness and verbal and figural memory performance. Further, we computed physical, social, and cognitive leisure activity scores from survey-based assessments and examined their associations with brain structure and declarative memory. To provide more accurate estimates of the trajectories and cross-domain correlations, we applied latent growth curve models controlling for potential confounders. Results : Less age-related thinning of the right (β = .92, p<.05) and left EC (β = .82, p<.05) was related to less declarative memory decline; and a thicker EC at baseline predicted less declarative memory loss (β = .54, p<.05). Higher baseline levels of physical (β = .24, p <.05), and social leisure activity (β = .27, p <.01) predicted less thinning of right EC. No relation was found between WMH or lacunes and declarative memory or between leisure activity and declarative memory. Higher education was initially related to more physical activity (β = .16, p<.05) and better declarative memory (β = .23, p<.001), which, however, declined steeper in participants with higher education (β = –.35, p<.05). Obese participants were less physically (β = –.18, p <.01) and socially active (β = –.13, p <.05) and had thinner left EC (β = –.14, p <.05) at baseline. Antihypertensive medication use (β = –.26, p <.05), and light-to-moderate alcohol consumption (β = –.40, p <.001) were associated with a smaller increase in the number of lacunes whereas a larger increase in the number of lacunes was observed in current smokers (β = .30, p <.05). Conclusions : Our results suggest complex relationships between cSVD MRI markers (total WMH, number of lacunes, right and left EC thickness), declarative memory, and confounding factors such as antihypertensive medication, obesity, and leisure activitiy. Thus, leisure activities and having good cognitive reserve counteracting this neurodegeneration. Several confounding factors seem to contribute to the extent or progression/decline of cSVD, which needs further investigation in the future. Since there is still no cure for cSVD, modifiable confounding factors should be studied more intensively in the future to maintain or promote brain health and thus cognitive abilities in older adults.