Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal Dementia Initiative including mutation carriers (MAPT, PGRN, C9ORF) and noncarrier relatives. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers and PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, according to the mutation group. Results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.