TY - JOUR
T1 - Longitudinal structural and metabolic changes in frontotemporal dementia
AU - Bejanin, Alexandre
AU - Tammewar, Gautam
AU - Marx, Gabe
AU - Cobigo, Yann
AU - Iaccarino, Leonardo
AU - Kornak, John
AU - Staffaroni, Adam M.
AU - Dickerson, Bradford C.
AU - Boeve, Bradley F.
AU - Knopman, David S.
AU - Gorno-Tempini, Marilu
AU - Miller, Bruce L.
AU - Jagust, William J.
AU - Boxer, Adam L.
AU - Rosen, Howard J.
AU - Rabinovici, Gil D.
N1 - Funding Information:
A. Bejanin, G. Tammewar, G.A. Marx, Y. Cobigo, L. Iaccarino, J. Kornak, A.M. Staffaroni, and B.C. Dickerson report no disclosures relevant to the manuscript. B.F. Boeve reports grants from GE Healthcare, NIH, Mangurian Foundation, FORUM Pharmaceuticals, C2N Diagnostics, Axovant, and personal fees from Scientific Advisory Board–Tau Consortium. D.S. Knopman reports grants from Biogen and Lilly A4 study and personal fees from Lundbeck Pharma and the DIAN study. B.L.M. receives grant support from the NIH/ NIA and the Centers for Medicare & Medicaid Services (CMS) as grants for the Memory and Aging Center. M.L.G. Tempini reports no disclosures relevant to the manuscript. B.L. Miller serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hill-blom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation (ABF). W.J. Jagust is a consultant for Genentech, Novartis, and Bioclinica. A.L. Boxer reports grants from BMS, Biogen, C2N, Tau Consortium, Bluefield Project to Cure FTD, CBD Solutions, Genentech, TauRx, Forum, and NIH; personal fees from AbbVie, Asceneuron, Celgene, Roche, Novartis, and Merck; and nonfinancial support from Quanterix. H.J. Rosen reports grants from Quest Diagnostics and Biogen Pharmaceuticals, outside the submitted work. G.D. Rabinovici receives research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, and Life Molecular Imaging; has received consulting fees from Eisai, Genentech, Merck, and Roche; speaking honorarium from GE Healthcare; and an honorarium as Associate Editor for JAMA Neurology. Go to Neurology.org/N for full disclosures.
Funding Information:
This research was funded by National Institute on Aging grants (P01 AG019724 to B.L.M. and H.J.R., P50-AG023501 to B.L.M., H.J.R., and G.D.R., P01-AG019724 to M.G., U01-AG052943 to M.G.-T.; R01-AG034570 to W.J.J.); National Institute of Neurologic Disorders and Stroke (R01-NS050915 to M.G.-T.; K24-DC015544 to M.G.-T.); and Fondation pour la Recherche Medicale (to A.B.).
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/7/14
Y1 - 2020/7/14
N2 - Objective To compare the sensitivity of structural MRI and 18F-fludeoxyglucose PET (18FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD).MethodsThirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2-4 MRI and 18FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls.ResultsAt baseline, patients with bvFTD showed bilateral temporal, dorsolateral, and medial prefrontal atrophy/hypometabolism that extended with time into adjacent structures and parietal lobe. In nfvPPA, baseline atrophy/hypometabolism in supplementary motor cortex extended with time into left greater than right precentral, dorsolateral, and dorsomedial prefrontal cortex. In svPPA, baseline atrophy/hypometabolism encompassed the anterior temporal and medial prefrontal cortex and longitudinal changes were found in temporal, orbitofrontal, and lateral parietal cortex. Across syndromes, there was substantial overlap in the brain regions showing volume and metabolism loss. Even though the pattern of metabolic decline was more extensive, metabolic changes were also more variable and sample size estimates were similar or higher for 18FDG-PET compared to MRI.ConclusionOur findings demonstrated the sensitivity of 18FDG-PET and structural MRI for tracking disease progression in FTD. Both modalities showed highly overlapping patterns of longitudinal change and comparable sample size estimates to detect longitudinal changes in future clinical trials.
AB - Objective To compare the sensitivity of structural MRI and 18F-fludeoxyglucose PET (18FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD).MethodsThirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2-4 MRI and 18FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls.ResultsAt baseline, patients with bvFTD showed bilateral temporal, dorsolateral, and medial prefrontal atrophy/hypometabolism that extended with time into adjacent structures and parietal lobe. In nfvPPA, baseline atrophy/hypometabolism in supplementary motor cortex extended with time into left greater than right precentral, dorsolateral, and dorsomedial prefrontal cortex. In svPPA, baseline atrophy/hypometabolism encompassed the anterior temporal and medial prefrontal cortex and longitudinal changes were found in temporal, orbitofrontal, and lateral parietal cortex. Across syndromes, there was substantial overlap in the brain regions showing volume and metabolism loss. Even though the pattern of metabolic decline was more extensive, metabolic changes were also more variable and sample size estimates were similar or higher for 18FDG-PET compared to MRI.ConclusionOur findings demonstrated the sensitivity of 18FDG-PET and structural MRI for tracking disease progression in FTD. Both modalities showed highly overlapping patterns of longitudinal change and comparable sample size estimates to detect longitudinal changes in future clinical trials.
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U2 - 10.1212/WNL.0000000000009760
DO - 10.1212/WNL.0000000000009760
M3 - Article
C2 - 32591470
AN - SCOPUS:85088177686
SN - 0028-3878
VL - 95
SP - E140-E154
JO - Neurology
JF - Neurology
IS - 2
ER -