PMID- 35486397 OWN - NLM STAT- MEDLINE DCOM- 20220503 LR - 20230908 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 5 IP - 4 DP - 2022 Apr 1 TI - Diagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration. PG - e229588 LID - 10.1001/jamanetworkopen.2022.9588 [doi] LID - e229588 AB - IMPORTANCE: The accurate diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is hampered by imperfect clinical-pathological correlations. OBJECTIVE: To assess and compare the diagnostic value of the magnetic resonance parkinsonism index (MRPI) and other magnetic resonance imaging-based measures of cerebral atrophy to differentiate between PSP, CBD, and other neurodegenerative diseases. DESIGN, SETTING, AND PARTICIPANTS: This prospective diagnostic study included participants with 4-repeat tauopathies (4RT), PSP, CBD, other neurodegenerative diseases and available MRI who appeared in the University of California, San Francisco, Memory and Aging Center database. Data were collected from October 27, 1994, to September 29, 2019. Data were analyzed from March 1 to September 14, 2021. MAIN OUTCOMES AND MEASURES: The main outcome of this study was the neuropathological diagnosis of PSP or CBD. The clinical diagnosis at the time of the MRI acquisition was noted. The imaging measures included the MRPI, cortical thickness, subcortical volumes, including the midbrain, pons, and superior cerebellar peduncle volumes. Multinomial logistic regression models (MLRM) combining different cortical and subcortical regions were defined to discriminate between PSP, CBD, and other pathologies. The areas under the receiver operating characteristic curves (AUROC) and cutoffs were calculated to differentiate between PSP, CBD, and other diseases. RESULTS: Of the 326 included participants, 176 (54%) were male, and the mean (SD) age at MRI was 64.1 (8.0) years. The MRPI showed good diagnostic accuracy for the differentiation between PSP and all other pathologies (accuracy, 87%; AUROC, 0.90; 95% CI, 0.86-0.95) and between 4RT and other pathologies (accuracy, 80%; AUROC, 0.82; 95% CI, 0.76-0.87), but did not allow the discrimination of participants with CBD. Its diagnostic accuracy was lower in the subgroup of patients without the canonical PSP-Richardson syndrome (PSP-RS) or probable corticobasal syndrome (CBS) at MRI. MLRM combining cortical and subcortical measurements showed the highest accuracy for the differentiation between PSP and other pathologies (accuracy, 95%; AUROC, 0.98; 95% CI, 0.97-0.99), CBD and other pathologies (accuracy, 83%; AUROC, 0.86; 95% CI, 0.81-0.91), 4RT and other pathologies (accuracy, 89%; AUROC, 0.94; 95% CI, 0.92-0.97), and PSP and CBD (accuracy, 91%; AUROC, 0.95; 95% CI, 0.91-0.99), even in participants without PSP-RS or CBS at MRI. CONCLUSIONS AND RELEVANCE: In this study, the combination of widely available cortical and subcortical measures of atrophy on MRI discriminated between PSP, CBD, and other pathologies and could be used to support the diagnosis of 4RT in clinical practice. FAU - Illan-Gala, Ignacio AU - Illan-Gala I AD - Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. AD - Atlantic Fellow for Equity in Brain Health at the University of California, San Francisco, Department of Neurology, University of California, San Francisco. AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. FAU - Nigro, Salvatore AU - Nigro S AD - Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, Tricase, Lecce, Italy. AD - Institute of Nanotechnology, National Research Council, Lecce, Italy. FAU - VandeVrede, Lawren AU - VandeVrede L AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Falgas, Neus AU - Falgas N AD - Atlantic Fellow for Equity in Brain Health at the University of California, San Francisco, Department of Neurology, University of California, San Francisco. AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Heuer, Hilary W AU - Heuer HW AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Painous, Celia AU - Painous C AD - Parkinson's Disease & Movement Disorders Unit, Hospital Clinic, Instituto de Investigaciones Biomedicas August Pi i Sunyer, CIBERNED, European Reference Network for Rare Neurological Diseases, Institut de Neurociencies, Universitat de Barcelona, Catalonia, Spain. FAU - Compta, Yaroslau AU - Compta Y AD - Parkinson's Disease & Movement Disorders Unit, Hospital Clinic, Instituto de Investigaciones Biomedicas August Pi i Sunyer, CIBERNED, European Reference Network for Rare Neurological Diseases, Institut de Neurociencies, Universitat de Barcelona, Catalonia, Spain. FAU - Marti, Maria J AU - Marti MJ AD - Parkinson's Disease & Movement Disorders Unit, Hospital Clinic, Instituto de Investigaciones Biomedicas August Pi i Sunyer, CIBERNED, European Reference Network for Rare Neurological Diseases, Institut de Neurociencies, Universitat de Barcelona, Catalonia, Spain. FAU - Montal, Victor AU - Montal V AD - Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. FAU - Pagonabarraga, Javier AU - Pagonabarraga J AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. AD - Movement Disorders Unit, Sant Pau Hospital and Biomedical Research Institute, Barcelona, Spain. AD - Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Kulisevsky, Jaime AU - Kulisevsky J AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. AD - Movement Disorders Unit, Sant Pau Hospital and Biomedical Research Institute, Barcelona, Spain. AD - Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Lleo, Alberto AU - Lleo A AD - Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. FAU - Fortea, Juan AU - Fortea J AD - Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. AD - Centro de Investigacion en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. FAU - Logroscino, Giancarlo AU - Logroscino G AD - Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, Tricase, Lecce, Italy. AD - Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy. FAU - Quattrone, Andrea AU - Quattrone A AD - Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, Catanzaro, Italy. FAU - Quattrone, Aldo AU - Quattrone A AD - Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy. AD - Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy. FAU - Perry, David C AU - Perry DC AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Gorno-Tempini, Maria Luisa AU - Gorno-Tempini ML AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Rosen, Howard J AU - Rosen HJ AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Grinberg, Lea T AU - Grinberg LT AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Spina, Salvatore AU - Spina S AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - La Joie, Renaud AU - La Joie R AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Rabinovici, Gil D AU - Rabinovici GD AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Miller, Bruce L AU - Miller BL AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Rojas, Julio C AU - Rojas JC AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Seeley, William W AU - Seeley WW AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. FAU - Boxer, Adam L AU - Boxer AL AD - Memory and Aging Center, Department of Neurology, University of California, San Francisco. LA - eng GR - K24 AG045333/AG/NIA NIH HHS/United States GR - K24 AG053435/AG/NIA NIH HHS/United States GR - P30 AG062422/AG/NIA NIH HHS/United States GR - P01 AG019724/AG/NIA NIH HHS/United States GR - K08 AG052648/AG/NIA NIH HHS/United States GR - K24 DC015544/DC/NIDCD NIH HHS/United States GR - R01 AG059794/AG/NIA NIH HHS/United States GR - R01 AG062758/AG/NIA NIH HHS/United States GR - RF1 NS050915/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220401 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM EIN - JAMA Netw Open. 2022 May 2;5(5):e2217977. PMID: 35612857 MH - Atrophy/diagnostic imaging MH - Cerebellum/pathology MH - *Corticobasal Degeneration MH - Female MH - Humans MH - Magnetic Resonance Imaging/methods MH - Male MH - *Neurodegenerative Diseases/diagnostic imaging MH - Prospective Studies MH - *Supranuclear Palsy, Progressive/diagnostic imaging/pathology PMC - PMC9055455 COIS- Conflict of Interest Disclosures: Dr Illan-Gala reported receiving personal fees from Nutricia, Esteve, and Neuraxpharm Spain outside the submitted work. Dr VandeVrede reported receiving personal fees from Retrotope outside the submitted work. Dr Lleo reporting serving on scientific advisory boards for Fujirebio-Europe, Nutricia, and Biogen and having filed a patent application of synaptic markers in neurodegenerative diseases. Dr Fortea reported receiving consulting fees from AC Inmune, Lundbeck, and Novartis; honoraria from Esteve, Roche, NovoNordisk, and Biogen Honoraria outside the submitted work; and holding an issued patent for markers of synaptopathy. Dr Grinberg reported receiving grants from the National Institutes of Health (NIH), Rainwater Charitable Foundation, and Weill Neuroscience Institute outside the submitted work. Dr Spina reported receiving consulting fees from Techspert.io, Precision Xtract, and Acsel Health outside the submitted work. Dr Rabinovici reported receiving grants from Avid, Eli Lilly and Co, GE Healthcare, Life Molecular Imaging, NIH, Alzheimer's Association, American College of Radiology, Rainwater Charitable Fund, and Genentech; receiving personal fees from Axon Neurosciences, Merck, Eli Lilly and Co, Eisai, Roche, Genentech, Johnson & Johnson, and GE Healthcare outside the submitted work; and serving as associate editor for JAMA Neurology. Dr Miller reported receiving grants from NIH and receiving royalties from Cambridge University Press, Guilford Publications, Johns Hopkins Press, Oxford University Press, Taylor & Francis Group, Elsevier, and UpToDate outside the submitted work. Dr Rojas reported serving as site principal investigator for Eli Lilly and Co and Eisai outside the submitted work. Dr Seeley reported receiving personal fees from BridgeBio, GLG Council, Guidepoint Global, and Corcept Therapeutics outside the submitted work. Dr Boxer reported receiving grants from NIH and grants from Rainwater Charitable Foundation during the conduct of the study; receiving grants from NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimers Drug Discovery Foundation and the Alzheimer's Association; consulting for Applied Genetic Therapies, Alector, Arkuda, Arvinas, AZTherapeutics, Boehringer Ingelheim, GlaxoSmithKline, Humana, Lundbeck, Oligomerix, Ono, Roche, Samumed, Stealth, Third Rock, Transposon, TrueBinding, and Wave; receiving stock and options from Alector Stock/options; receiving options from Arvinas, Arkuda, AZTherapies, and True Binding; receiving grants from Biogen, Eisai, and Regeneron; and receiving personal fees from Denali, GlaxoSmithKline, Humana, Boeringher Ingelheim, Oscotec, Oligomerix, Roche, Transposon, and Wave outside the submitted work. No other disclosures were reported. EDAT- 2022/04/30 06:00 MHDA- 2022/05/04 06:00 PMCR- 2022/04/29 CRDT- 2022/04/29 11:33 PHST- 2022/04/29 11:33 [entrez] PHST- 2022/04/30 06:00 [pubmed] PHST- 2022/05/04 06:00 [medline] PHST- 2022/04/29 00:00 [pmc-release] AID - 2791726 [pii] AID - zoi220292 [pii] AID - 10.1001/jamanetworkopen.2022.9588 [doi] PST - epublish SO - JAMA Netw Open. 2022 Apr 1;5(4):e229588. doi: 10.1001/jamanetworkopen.2022.9588.