A multivariate metabolic imaging marker for behavioral variant frontotemporal dementia

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.