Abstract
INTRODUCTION: The heterogeneity of behavioral variant frontotemporal dementia (bvFTD) calls for multivariate imaging biomarkers. METHODS: We studied a total of 148 dementia patients from the Feinstein Institute (Center-A: 25 bvFTD and 10 Alzheimer's disease), Technical University of Munich (Center-B: 44 bvFTD and 29 FTD language variants), and Alzheimer's Disease Neuroimaging Initiative (40 Alzheimer's disease subjects). To identify the covariance pattern of bvFTD (behavioral variant frontotemporal dementia-related pattern [bFDRP]), we applied principal component analysis to combined 18F-fluorodeoxyglucose-positron emission tomography scans from bvFTD and healthy subjects. The phenotypic specificity and clinical correlates of bFDRP expression were assessed in independent testing sets. RESULTS: The bFDRP was identified in Center-A data (24.1% of subject × voxel variance; P < .001), reproduced in Center-B data (P < .001), and independently validated using combined testing data (receiver operating characteristics-area under the curve = 0.97; P < .0001). The expression of bFDRP was specifically elevated in bvFTD patients (P < .001) and was significantly higher at more advanced disease stages (P = .035:duration; P < .01:severity). DISCUSSION: The bFDRP can be used as a quantitative imaging marker to gauge the underlying disease process and aid in the differential diagnosis of bvFTD.