Longitudinal Progression of White Matter Hyperintensities and Disease Severity in bvFTD

Behavioral variant frontotemporal dementia (bvFTD) is associated with increased white matter hyperintensity (WMH) burden, which relates to disease severity and cognition. Yet longitudinal WMH progression in bvFTD remains understudied in Latin America. We included 28 participants from the Instituto Peruano de Neurociencias (20 healthy controls [HC], 8 bvFTD) with MMSE, CDR, T-ADLQ, and MRI assessments at baseline and follow-up (mean interval 2.6±1.0 years). Linear mixed-effects models tested group-by-time effects on clinical and WMH measures. Partial Spearman correlations tested associations between annual WMH-volume change and annual change in MMSE, CDR sum-of-boxes, and T-ADLQ. Analyses adjusted for baseline age, education, sex, and total intracranial volume, and were FDR-corrected. Compared with HC, bvFTD showed steeper annual MMSE decline (β=−2.83; qFDR<.001) and greater annual increases in CDR sum-of-boxes (β=1.50; qFDR<.001), T-ADLQ (β=1.07; qFDR=.041), WMH volume (β=1.07; qFDR<.001), and WMH count (β=2.93; qFDR<.001). Greater WMH-volume increase was linked to faster CDR worsening (p=.013; qFDR=.039) and nominally associated with MMSE decline (p=.046; qFDR=.069). bvFTD patients showed greater longitudinal WMH accumulation alongside faster cognitive and functional decline than HC. Greater WMH progression was linked to worsening disease severity, supporting its potential as a clinically relevant marker of bvFTD progression in this understudied cohort.