Abstract 51: Effects of Vascular Risk Factors on Microstructural White Matter: A Voxel-Based Longitudinal Diffusion Tensor Imaging Study

Background: Diabetes mellitus type II (DMT2) and hypertension (HTN) have been reported as increasing the risk of dementia. Because recent cross-sectional diffusion tensor imaging (DTI) studies have identified association between vascular risk factors (VRF) and microstructural white matter (WM) abnormalities in elderly, longitudinal DTI studies are needed to determine whether VRF may be associated with accelerated WM degeneration over time. Methods: 114 cognitively normal participants from University of California, Davis Alzheimer’s Disease Center, aged 73.9±6.7, received a comprehensive clinical evaluation and brain MRI including T1-weighted and DTI sequences on two dates (mean delay: 3.3 years). Baseline and follow-up FA maps were calculated, aligned, and subtracted to provide FA change ([[Unable to Display Character: ∆]]FA) maps and warped to a common template (MDT). Coregistration of baseline and follow-up T1 maps to MDT enabled computation of Jacobian images (i.e. the local contraction factor). VRF score (VRFS) was computed as the sum of DMT2, HTN and hyperlipidemia (HYP) incidence based on the subject’s medical history. We then used voxel-based linear regressions to relate annual [[Unable to Display Character: ∆]]FA and Jacobian determinants to VRFS, adjusting for potential confounders. Resulting T maps were corrected for multiple comparisons. Results: Poorer VRF score was associated with higher rate of [[Unable to Display Character: ∆]]FA loss and of GM atrophy with regions most heavily implicated including the corpus callosum and the frontal GM (see Figure1). Conclusions: This is one of very few studies of longitudinal DTI change in the elderly. DMT2, HTH and HYP are associated with accelerated WM degeneration and GM atrophy in areas whose integrity is known to be reduced in mild cognitive impairment and dementia. Future work should clarify the independent role of these vascular risk factors in accelerating brain aging.