Better cardiovascular health, measured by Life's Simple 7, is associated with lower white matter hyperintensity burden and greater cerebral blood flow over time

Background Lifestyle factors have been studied for dementia risk, but few studies have comprehensively assessed both Alzheimer's disease (AD) and cerebrovascular disease (CBVD) pathologies. Objective Our research aims to determine the relationships between lifestyle and dementia pathologies. Methods We analyzed data from 1208 Wisconsin Registry for Alzheimer's Prevention (WRAP) participants. The cohort is enriched for participants with a family history of AD and a higher proportion of APOE ε4 carriers (n = 478); participants are primarily female (n = 827), non-Hispanic white (n = 1088), and highly educated (≥3 years professional or college education; n = 803), with an average baseline age of 64. Life's Simple Seven (LS7) scores were calculated from questionnaire data and clinical vitals. Brain health outcomes included CBVD biomarkers (white matter hyperintensities and arterial spin labeling [ASL] cerebral perfusion), AD biomarkers (amyloid Pittsburgh compound B index and tau standardized uptake value ratio Mayo meta-temporal composite), and cognitive outcomes (Preclinical Alzheimer Cognitive Composite Score 3 [PACC3], Delayed Recall, Immediate Learning, and Executive Function). Results Higher LS7 scores were significantly associated with lower white matter hyperintensity burden and higher ASL perfusion at the 6–8 year interval, with nominal associations observed at earlier time points and for global cognition (PACC3). No consistent associations were observed with amyloid or tau PET measures. Conclusions This study provides evidence that the beneficial effects of LS7 on cognition are primarily through cerebrovascular pathways rather than through AD pathology.