O2‐09‐02: Midlife and Late Life Vascular Risk Factors and Microstructural Integrity Assessed Using Diffusion Tensor Imaging: The Aric‐NCS Study

The presence of vascular risk factors, particularly in midlife, appears to increase risk of subsequent cognitive decline and dementia. Differences in microstructural integrity on diffusion MRI also appear related to differences in cognitive performance and may partially mediate the adverse consequences of vascular risk factors on cognition. However, current studies on microstructural integrity and vascular risk factors are exclusively-cross sectional, and none have evaluated relations of midlife risk factors to late life microstructural integrity. Our study sample included 1851 participants of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) who completed 3T MRI, including a diffusion tensor imaging pulse sequence. We assessed the association between midlife (measured at the baseline ARIC visit in 1987-1989, when participants were, on average 53 years old) and late life (concurrent with the MRI, on average 24 years later, in 2011-2013) measures of blood pressure, blood lipids, and blood glucose with total or regional mean white matter mean diffusivity (MD) and fractional anisotropy (FA). We also considered whether additionally adjusting for white matter hyperintensity (WMH) volumes in our regression models impacted these associations. Elevated systolic and diastolic blood pressure (BP), at both midlife and late life, was generally associated with worse total and regional FA and MD in late life. Elevated blood glucose at midlife, but not late life, was also associated with worse total and regional MD, although there was little evidence linking midlife blood glucose to FA overall or in most regions considered. Associations between lipid levels and total or regional MD or FA were generally null, with a few exceptions. Additional adjustment for WMH slightly attenuated, but did not nullify observed associations of BP or midlife blood glucose with measures of FA or MD (e.g., difference in standardized FA per 10 mm Hg increase in midlife systolic BP before WMH adjustment: -0.056, 95%CI: -0.091, -0.021; after WMH adjustment -0.048, 95%CI: -0.076, -0.019). Hypertension and diabetes may lead to poor or declining cognition through mechanisms that disrupt microstructural integrity. DTI measures of FA and MD provide unique information on underlying processes not captured by measures of WMH.