Non‐imaging measures to predict variability in white matter changes relevant to VCID

Background Small vessel disease (SVD) is a common vascular contributor to cognitive impairment and dementia. In this work, we evaluated and compared non‐imaging measures that can predict variability in SVD related white matter (WM) damage in a population‐based sample. Method We identified 752 participants in the population‐based sample of Mayo Clinic Study of Aging (≥50 years of age), who had at least 2 diffusion tensor imaging (DTI) scans and white matter hyperintensity (WMH) assessments along with baseline demographics, systemic vascular health, lifestyle, motor impairment, behavioral symptoms, and plasma markers (Summarized in Figure 1). We computed the WM markers of SVD: fractional anisotropy of genu of the corpus callosum (Genu‐FA) representative of early WM changes, WMH representative of late WM changes, and Vascular WM score (combination of Genu‐FA and WMH). Using all available data, we fit linear mixed effect models and evaluated predictors of WM markers by considering each category of features independently (with demographics) as well as by combining all categories of features Result Plasma, gait, systemic vascular, and life‐style measures were significant predictors of all three WM markers of SVD (Figure 2). The predictors of early and late WM slightly differed such that there were no additional significant contributions from behavioral and plasma measures to Genu‐FA. In the final composite models shown in Table 1, higher gait speed, lower number of cardiovascular and metabolic conditions (CMC) and lower Unified Parkinson’s disease rating scale scores were associated with better Genu‐FA whereas higher CMC, Beck Anxiety Inventory scores (BAI), and glial acidic protein (GFAP) levels were associated with higher burden of WMH. Conclusion Our observations evaluated the non‐imaging markers of greater WM damage that are relevant to vascular contributions to cognitive impairment to dementia (VCID). We found that in addition to higher vascular risk, worse plasma GFAP, gait measures, and BAI scores were predictors of greater WM damage. Some non‐imaging markers were more associated with early WM changes and others with late WM changes.