The study of modifiable lifestyle factors is inherently appealing—it aims to modify dementia risk in a way that pharmacological medicine has yet to deliver. While the incidence of dementia provides the clearest measure for dementia risk, it doesn’t capture finer changes in brain structure. Age-related changes in white matter are linked to changes in cognitive function, associated with an increased risk of dementia, and may serve as a more sensitive index of brain-related changes that precede dementia.
Using data from Lifebrain, a European consortium of MRI cohorts, structural equation models will be applied to test the associations between lifestyle factors and white matter microstructure in older adults. Latent variables will be derived from lifestyle measures (the predictors) and from multi-modal indices of white matter (the outcome). Latent factors are advantageous as they yield more reliable estimates of the target concepts and are less susceptible to measurement errors. To test the generalizability of our results, we will replicate our analysis on a second Lifebrain cohort. Our results will identify which modifiable lifestyle factors account for the most variance in white matter microstructure. This information will indicate the strongest candidates for future multi-factor interventions aimed at promoting healthy aging.