P1‐442: WHITE MATTER HYPERINTENSITIES AND COGNITIVE DECLINE IN FRONTO‐TEMPORAL DEMENTIA VARIANTS

White matter hyperintensities (WMHs) are areas of increased signal on FLAIR images which indicate the presence of small-vessel disease in the brain. They are associated with increased cognitive deficits in aging as well as Alzheimer's disease. We investigated the differences in WMH burden between variants of frontotemporal dementia (i.e. behavioral, semantic, and progressive non-fluent aphasia abbreviated as bv-FTD, sv-FTD, and pnfa-FTD) and their relation to cognitive decline. Longitudinal imaging/clinical data were obtained from the frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset for normal controls, individuals with bv-FTD, sv-FTD, and pnfa-FTD (NControl=120,Nbv-FTD=59,Nsv-FTD=35,Npnfa-FTD=30). WMHs were segmented using a previously validated pipeline based on location and intensity features from T1w and FLAIR images [Dadar et al., NeuroImage 2017]. WMH volumes were calculated per each brain lobe and hemisphere. Mixed-effects models were used to assess the WMH differences between controls and FTD patients (Model 1: WMH∼1+Cohort+Age+1|ID+1|Site) and their effect on cognition, as measured by the Mini-Mential State Examination (MMSE) scores (Model 2: MMSE∼1+ WMH+Cohort+WMH:Cohort+Age+1|ID+1|Site). In Model 1, the variable of interest was Cohort (i.e. Control vs bv-FTD, sv-FTD, and pnfa-FTD). In Model 2, the variable of interest was the interaction between Cohort and WMH load, denoted by WMH:Cohort. ID and Site were considered as categorical random effects. WMHs increased significantly with age for all lobes (p<0.01). Compared to controls, bv-FTD patients had significantly higher WMH loads in the frontal (βRight=0.805,pRight<0.0001, βLeft=0.796,pLeft<0.0001), parietal (βRight=0.647,pRight<0.0001, βLeft=0.411,pLeft=0.002), and occipital lobes (βRight=0.345,pRight=0.01, βLeft=0.302,pLeft=0.02), sv-FTD patients had higher WMH loads in the parietal (βRight=0.465,pRight=0.002, βLeft=0.373,pLeft=0.02) and left frontal (βLeft=0.325,pLeft=0.03) and temporal (βRight=0.288,pRight=0.05, βLeft=0.469,pLeft=0.003) lobes, and pnfa-FTD patients had higher WMH loads in the right parietal lobe (βRight=0.423,pRight=0.009) (Fig.1). Compared to controls, decrease in MMSE was associated with increased WMH load in frontal lobe in bv-FTD (βRight=−0.309,pRight=0.001, βLeft=−0.373,pLeft=0.0001) and pnfa-FTD patients (βRight=−0.686,pRight<0.0001, βLeft=−0.685,pLeft<0.0001), as well as parietal lobe in pnfa-FTD patients (βRight=−0.443,pRight=0.02, βLeft=−0.449,pLeft=0.001), and right parietal lobe in bv-FTD patients (βRight=−0.215,pRight=0.02) (Fig.2).

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