Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease
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(2020) 12:148
RESEARCH
Open Access
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease Ellen H. Singleton1* , Yolande A. L. Pijnenburg1, Carole H. Sudre2, Colin Groot1, Elena Kochova1, Frederik Barkhof3,4, Renaud La Joie5, Howard J. Rosen5, William W. Seeley5, Bruce Miller5, M. Jorge Cardoso2,6, Janne Papma7,8, Philip Scheltens1, Gil D. Rabinovici5,9,10,11 and Rik Ossenkoppele1,12
Abstract Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinicoanatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvADtAD), MRI anterior-DMN-ratios (bvAD patients, p < 0.001 c bvAD and tAD > controls, p < 0.01, bvAD and tAD > bvFTD, p < 0.001 d Controls > patients, p < 0.001, tAD < bvFTD, p < 0.05 e Controls > patients, p < 0.001 f bvAD and bvFTD > tAD, p < 0.01
Singleton et al. Alzheimer's Research & Therapy
(2020) 12:148
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Fig. 1 Patterns of hypometabolism of patients versus cognitively normal controls. a Surface rendering of T-maps showing hypometabolic regions in patient groups compared to cognitively healthy controls. Contrasts were adjusted for age and sex. b Surface rendering of significant voxels from contrasts between patients and controls, displayed at p < 0.05, family-wise error corrected, extent threshold k = 50. c Overlay of the T-maps from the voxel-wise comparison of FDG-PET SUVr between patients and controls. Overlays are displayed at p < 0.05, family-wise error corrected, extent threshold k = 50. Cerebellum was removed for visualization purposes
different functional network templates showed a simila
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