How white matter hyperintensities impacts Alzheimer's disease and frontotemporal dementia across underrepresented Latin American samples

Background: White matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer's disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD. Method: A total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high-resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined. Result: Total and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum-hippocampus bundle in AD. Conclusion: Enhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain-specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age-related increase in WMH.