Rest–activity functioning is related to white matter microarchitecture and modifiable risk factors in older adults at-risk for dementia

Study Objectives: Growing evidence demonstrates pronounced alterations in rest-activity functioning in older adults at-risk for dementia. White matter degeneration, poor cardiometabolic functioning, and depression have also been linked to a greater risk of decline; however, limited studies have examined the white matter in relation to rest-activity functioning in at-risk older adults. 

Methods: We investigated associations between nonparametric actigraphy measures and white matter microarchitecture using whole-brain fixel-based analysis of diffusion-weighted imaging in older adults (aged 50 years or older) at-risk for cognitive decline and dementia. The fixel-based metrics assessed were fiber density, fiber cross-section, and combined fiber-density, and cross-section. Interactions between rest-activity functioning and known clinical risk factors, specifically body mass index (BMI), vascular risk factors, depressive symptoms and self-reported exercise, and their association with white matter properties were then investigated. 

Results: Sixty-seven older adults were included (mean = 65.78 years, SD = 7.89). Lower relative amplitude, poorer 24-h synchronization and earlier onset of the least active 5-h period were associated with reductions in markers of white matter atrophy in widespread regions, including cortico-subcortical and cortical association pathways. Preliminary evidence was also found indicating more pronounced white matter alterations in those with lower amplitude and higher BMI (β = 0.25, 95% CI [0.05, 0.46]), poorer 24-h synchronization and more vascular risk factors (β = 0.17, 95% CI [-0.02, 0.36]) and earlier onset of inactivity and greater depressive symptoms (β = 0.17, 95% CI [0.03, 0.30]). 

Conclusions: These findings highlight the complex interplay between rest-activity rhythms, white matter, and clinical risk factors in individuals at-risk for dementia that should be considered in future studies.