Cognitive Aging and Cerebrovascular Health: Role of White Matter Lesions and Cardiorespiratory Fitness

Aging is associated with an increase in white matter lesions (WMLs) and decline in cognitive performance. Cardiorespiratory fitness (CRF) is a modifiable cardiovascular risk factor which is hypothesized to mitigate the accumulation of WMLs and support cognitive aging, and therefore is a possible therapeutic target for intervention. Path analysis approach has not been taken to understand the direct and indirect effects of CRF and WMLs on cognition. Additionally, the effect of CRF on periventricular WMLs (PVWMLs) and deep WMLs (DWMLs) and their effect on cognition has not been examined. We examined these relations in middle-aged and older-aged adults (n=118; 55-80 years); cognitive performance was assessed on measures of processing speed (PS) and executive functions (EF). We hypothesized that after adjusting for sex and education, higher age would be related to lower CRF, more PVWMLs and DWMLs and worse cognitive performance by both the direct path and indirectly through CRF; specifically, higher CRF would be related to less PVWMLs and better cognitive performance directly and indirectly through WMLs; and higher PVWML volume would be associated with poorer cognitive performance. Our hypotheses were partially supported such that age was related to lower CRF, more WMLs, and worse cognitive performance both directly and indirectly; higher CRF was related to less PVWMLs and DWMLs and better performance on measures of EF; only PVWMLs were related to better performance on the measure of EF. The study sets a mechanistic framework to understand the relation between CRF, WMLs, and cognition which can inform future intervention studies.