Abstract 221: Regional Vulnerability within White Matter tracts to White Matter Hyperintensities: a Diffusion Tensor Imaging Tractography Study

Abstract

Background: Characterizing the impact of cerebral white matter (WM) damage on age related cognitive decline is of growing interest. White matter hyperintensities (WMH) and reduced microstructural WM integrity, as expressed by diffusion tensor imaging (DTI), have been associated with increased risk of clinically cognitive decline in the elderly, but the regional vulnerability within certain WM tracts to WMH is not well understood. Characterizing the implication and interactions of microstructural integrity and WMH within specific WM tracts would further elucidate mechanisms of cognitive decline in normal aging. Methods: 410 cognitively normal individuals from the Offspring Framingham Heart Study, aged 72.5±7.5 ([54.2; 104.9]), received a comprehensive clinical evaluation and brain MRI including FLAIR and DTI sequences. WM tractography was performed from DTI using FSL tools, resulting in 27 fiber tracts maps for each subject. WMHs were detected on FLAIR scans using a standardized protocol and coregistered to the subject DTI space. The mean fractional anisotrophy (mFA) within each tract was computed. Superimposition of WMH masks onto fiber tracts maps was used to calculate the overlap ratio of WMH (WMHor) within each tract. For each tract, mFA was regressed against the age and tract size and resulting residuals related to WMHor using a linear regression model. Results: The highest rates of WMHor were found within the thalamic radiations (range: [0- 28%]) and the inferior longitudinal fasciculi ([0- 29%]). Lower mFA was independently associated with larger WMHor within almost all association and projection fibers (p values<0.05). Correcting for the overall WMH burden did not significantly alter the results. Discussion: Regional mean FA has been previously associated with the overall WMH burden. We extended this finding by showing that, independently of the overall WM injury, microstructural WM integrity was associated with WMH within specific fiber tracts. Further investigations are needed to detangle the impact of specific tract disruption from that of more generalized subtle WM injury on cognitive decline.