To examine whether brain volume loss measured by MRI is associated with clinical severity and progression over time in individuals with CSF1R-ALSP.

CSF1R-ALSP is a rare, autosomal-dominant, neurodegenerative disorder caused by colony-stimulating factor-1 gene (CSF1R) loss-of-function mutations and characterized by brain white matter demyelination, swollen axons, pigmented glial cells, and brain atrophy. Clinical symptoms include cognitive, neuropsychiatric, and motor dysfunction. Average age at onset is in the 4^th decade. No approved therapies available.

Data from 42 participants (24 symptomatic and 18 prodromal) with confirmed CSF1R mutations was analyzed. Participants were sub-grouped by quartiles of baseline MoCA/CBFS, the most impaired quartile of participants had the least brain volume (e.g., larger ventricles, less gray matter, and smaller corpus callosum) at study baseline. When participants who showed clinical decline over time were compared to those stable or improved, participants with clinical decline had greater brain volume loss on all MRI measures. Statistically significant correlations between 12-month change from baseline in MoCA and MRI evaluations were observed (ventricles, r=-0.65; gray matter volume, r=0.58; and corpus callosum, r=0.62). Directionally consistent findings were observed between CBFS and MRI measures.