Cross-Sectional and Longitudinal Patterns of Atrophy in Thalamic and Deep Gray Matter Nuclei in Frontotemporal Dementia

INTRODUCTIONFrontotemporal dementia involves progressive atrophy in deep gray matter nuclei, including the thalamus and basal ganglia (such as the caudate, putamen, nucleus accumbens, and globus pallidus), which are critical for cognition and behavior. This study examined cross-sectional and longitudinal atrophy using a state-of-the-art multi-atlas segmentation method sTHOMAS. METHODST1-weighted MRI scans from 274 participants at baseline and 237 at follow-up obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative database were analyzed using sTHOMAS. Group differences were assessed using ANCOVA, adjusting for age, gender and intracranial volume as covariates. RESULTSAtrophy was significant in the mediodorsal, pulvinar, anterior ventral nuclei, nucleus accumbens, and claustrum, with bvFTD most affected cross-sectionally. Longitudinally, the nucleus accumbens, mediodorsal, and pulvinar nuclei declined further. Atrophy correlated with naming (mediodorsal), working memory (ventrolateral posterior), and executive dysfunction (nucleus accumbens) neuropsychological tests. DISCUSSIONThese findings highlight progressive, nucleus-specific atrophy in FTD and emphasize the importance of cross-sectional as well as longitudinal imaging and sex-specific analyses in understanding disease progression.