Subcortical and Deep Cortical Atrophy in Frontotemporal Dementia due to Granulin Mutations

BACKGROUND/AIMS Parkinsonism is often associated with symptoms of frontotemporal dementia (FTD), but its pathogenesis has been largely neglected. In genetic inherited FTD-related granulin (GRN) mutations, parkinsonism is an early sign, and it is more common than in sporadic disorders. Our aim was to study grey matter (GM) volume changes in subcortical and deep cortical regions in GRN-related FTD. METHODS A total of 33 FTD patients (13 carriers of the GRN mutation, GRN+, and 20 non-carriers, GRN-) and 12 healthy controls (HC) were included in the study. Each subject underwent an MRI examination (1) for voxel-based morphometry to study GM differences in cortical and subcortical regions, and (2) for a region of interest approach using a probabilistic atlas of subcortical regions (caudate nucleus, putamen, thalamus and amygdala) to assess the regional differences. RESULTS The GRN+ group showed greater damage in frontotemporal regions than the GRN- group. The FTD patients had greater GM atrophy in the caudate nucleus and in the thalamus bilaterally than the HC. Damage to these subcortical and deep cortical regions was greater in the GRN+ than in the GRN- patients. DISCUSSION Subcortical and deep cortical involvement is a key feature of FTD, and more pronounced in GRN-related disease. Damage to the caudate region in GRN+ patients may explain the parkinsonism frequently associated since the early stages of the disease.