Clinical and Biological Correlates of White Matter Hyperintensities in Patients with #Behavioral-variant Frontotemporal #Dementia and #Alzheimer Disease

To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses.

Methods: 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI, clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm, and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy and performance across different cognitive domains were assessed.

Results: Total WMH volumes were larger in bvFTD than AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. bvFTD and AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD.

Conclusion: Increased WMH are common in bvFTD and AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Further, increased WMH in different regions contribute to cognitive deficits.