O3-04-01: biomarkers for capturing amyloid-independent effects of vascular health on cognitive decline

We recently reported that microstructural integrity measured using DTI, specifically fractional anisotropy (FA) of the tracts in the anterior corpus callosum (or genu), showed sensitivity and specificity to cerebrovascular damage. These effects persisted after accounting for amyloid and tau pathologies using PET. In this work, we focused on amyloid negative (A-) individuals in the population to evaluate the impact of baseline genu FA on longitudinal cognitive decline (global and specific domains – attention, memory, visuospatial, language). We also compared the effect of genu FA to the effect of vascular positivity (V+) as previously defined based on FLAIR-MRI. We identified 1192 participants from the population-based sample of Mayo Clinic Study of Aging who were at least 60 years of age with amyloid PET (PiB), DTI, and FLAIR exams and categorized individuals into A+/A- (using amyloid SUVR>1.48) and V+/V-(determined by combination of presence of infarctions and/or high white matter hyperintensities using a cut-point of 1.7% of total intracranial volume). In a subset of 712 A- individuals with ≥1 cognitive visits after imaging, we fit mixed effect models with age, sex, visit number, time, genu FA, and genu FA x time as predictors and longitudinal cognition (global and domain-specific) as outcome. Additionally, we fit models with V+ instead of genu FA and compared the model fits based on Akaike information criteria (AIC). The frequency of individuals within the A+/A- and V+/V- subgroups are shown in Figure 1. In the models with genu FA, baseline FA was associated with baseline global cognition and decline (p<0.001). Genu FA was also associated with baseline domain-specific scores and decline in each domain (p<0.05) except baseline memory (p=0.73). The models with V+ instead of genu FA had significantly higher AIC suggesting that genu FA may provide more information than V+ based on FLAIR.