Drawing on the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS), this study aimed to investigate the direct and indirect associations between vascular risk factors/cardiovascular disease (CVD), pharmacological treatment (of CVD), and white matter hyperintensity (WMH) burden on overall cognition and decline trajectories in a cognitively diverse sample of older adults.

Participants were 1,049 cognitively diverse older adults drawn from a larger NACC data repository of 22,684 participants whose data was frozen as of December 2019. The subsample included only participants who were aged 60-97 (56.7% women) who completed at least one post-baseline neuropsychological evaluation, had medication data, and both T1 and FLAIR neuroimaging scans. Cognitive composites (Memory, Attention, Executive Function, Language) were derived factor analytically using harmonized data. Baseline WMH volumes were quantified using UBO Detector. Baseline health screening and medication data was used to determine overall CVD burden and total medication. Longitudinal latent growth curve models were estimated adjusting for demographics.

More CVD medication was associated with greater CVD burden; however, no direct effects of medication were found on any of the cognitive composites or WMH volume. While no direct effects of CVD burden on cognition (overall or rate of decline) were observed, instead we found that greater CVD burden had small, but significant, negative indirect effects on Memory, Attention, Executive Functioning and Language (all p’s < .01) after controlling for CVD medication use. Whole brain WMH volume served as the mediator of this relationship, as it did for an indirect effect of baseline CVD on 6-year rate of decline in Memory and Executive function.

Findings from this study were generally consistent with previous literature and extend extant knowledge regarding the direct and indirect associations between CVD burden, pharmacological treatment, and neuropathology of presumed vascular origin on cognitive decline trajectories in an older adult sample. Results reveal the subtle importance of CVD risk factors on late life cognition even after accounting for treatment and WHM volume and highlight the need for additional research to determine sensitive windows of opportunity for intervention.