Caudate-Predominant Striatal Dopaminergic Deficit Distinguishes Behavioral Variant of Frontotemporal Dementia With Parkinsonism From Other Parkinsonian Syndromes

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BACKGROUND: Behavioral variant of frontotemporal dementia (bvFTD) often presents with parkinsonism. Our study aimed to characterize the dopaminergic deficit pattern in bvFTD-parkinsonism (bvFTD-P) using dopamine transporter (DAT) positron emission tomography (PET) and to assess its potential value in differentiating bvFTD-P from progressive supranuclear palsy (PSP), multiple system atrophy-parkinsonism (MSA-P), and Parkinson disease (PD). METHODS: A total of 30 bvFTD-P patients underwent 11 C-CFT or 18 F-FP-CIT PET and were compared with 71 patients with PSP, 41 with MSA-P, 61 with PD, and 43 healthy controls (HC). DAT binding values in the caudate, anterior putamen, and posterior putamen, as well as caudate/anterior putamen (C/AP) and caudate/posterior putamen (C/PP) ratios, were analyzed with generalized linear models. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracy of DAT binding values and ratios. RESULTS: BvFTD-P patients exhibited significantly reduced DAT binding in the caudate, anterior putamen, and posterior putamen compared with HC (all P <0.01), with a caudate-predominant deficit pattern (lower C/AP and C/PP ratios), contrasting with the putamen-predominant loss observed in PSP, MSA-P, and PD. This caudate-predominant pattern was replicated in the independent 18 F-FP-CIT cohort. ROC analysis demonstrated that the C/PP ratio provided superior discriminatory performance between bvFTD-P and HC or other parkinsonian syndromes than absolute binding values. Furthermore, lateralization of striatal DAT reduction corresponded to the side of predominant motor symptoms. CONCLUSIONS: The caudate-predominant pattern of striatal dopaminergic deficit in bvFTD-P may serve as a useful imaging biomarker for differentiating it from PSP, MSA-P, and PD.

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