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

Abstract

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). 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. 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. 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.