Continuous β-Amyloid CSF/PET Imbalance Model to Capture Alzheimer Disease Heterogeneity.

Autor: Mastenbroek SE; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Sala A; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Vállez García D; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Shekari M; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Salvadó G; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Lorenzini L; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Pieperhoff L; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Wink AM; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Lopes Alves I; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Wolz R; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Ritchie C; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Boada M; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Visser PJ; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Bucci M; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Farrar G; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Hansson O; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Nordberg AK; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Ossenkoppele R; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Barkhof F; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Gispert JD; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Rodriguez-Vieitez E; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom., Collij LE; From the Department of Radiology and Nuclear Medicine (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Vrije Universiteit Amsterdam, Amsterdam University Medical Center, location VUmc; Amsterdam Neuroscience (S.E.M., D.V.G., L.L., L.P., A.M.W., F.B., L.E.C.), Brain Imaging, the Netherlands; Clinical Memory Research Unit (S.E.M., G.S., O.H., R.O., L.E.C.), Department of Clinical Sciences Malmö, Lund University; Division of Clinical Geriatrics (A.S., M. Bucci, A.K.N., E.R.-V.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Coma Science Group (A.S.), GIGA-Consciousness, University of Liège; Centre du Cerveau2 (A.S.), University Hospital of Liège, Belgium; Barcelonaβeta Brain Research Center (BBRC) (M.S., G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (M.S., J.D.G.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (M.S., J.D.G.), Instituto de Salud Carlos III, Madrid; Universitat Pompeu Fabra (M.S.), Barcelona, Spain; Brain Research Center (I.L.A.), Amsterdam, the Netherlands; IXICO (R.W.), London; Centre for Clinical Brain Sciences (C.R.), University of Edinburgh, United Kingdom; Ace Alzheimer Center Barcelona (M. Boada), Universitat Internacional de Catalunya, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED) (M. Boada), Instituto de Salud Carlos III, Madrid, Spain; Alzheimer Center Amsterdam (P.J.V., R.O.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Amsterdam Neuroscience (P.J.V.), Neurodegeneration; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; Division of Neurogeriatrics (P.J.V.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging (M. Bucci, A.K.N.), Karolinska University Hospital, Stockholm, Sweden; GE Healthcare (G.F.), Amersham, United Kingdom; Memory Clinic (O.H.), Skåne University Hospital, Malmö, Sweden; and Centre for Medical Image Computing (F.B.), and Queen Square Institute of Neurology, UCL, London, United Kingdom.
Jazyk: angličtina
Zdroj: Neurology [Neurology] 2024 Jul 09; Vol. 103 (1), pp. e209419. Date of Electronic Publication: 2024 Jun 11.
DOI: 10.1212/WNL.0000000000209419
Abstrakt: Background and Objectives: Discordance between CSF and PET biomarkers of β-amyloid (Aβ) might reflect an imbalance between soluble and aggregated species, possibly reflecting disease heterogeneity. Previous studies generally used binary cutoffs to assess discrepancies in CSF/PET biomarkers, resulting in a loss of information on the extent of discordance. In this study, we (1) jointly modeled Aβ-CSF/PET data to derive a continuous measure of the imbalance between soluble and fibrillar pools of Aβ, (2) investigated factors contributing to this imbalance, and (3) examined associations with cognitive trajectories.
Methods: Across 822 cognitively unimpaired (n = 261) and cognitively impaired (n = 561) Alzheimer's Disease Neuroimaging Initiative individuals (384 [46.7%] females, mean age 73.0 ± 7.4 years), we fitted baseline CSF-Aβ 42 and global Aβ-PET to a hyperbolic regression model, deriving a participant-specific Aβ-aggregation score (standardized residuals); negative values represent more soluble relative to aggregated Aβ and positive values more aggregated relative to soluble Aβ. Using linear models, we investigated whether methodological factors, demographics, CSF biomarkers, and vascular burden contributed to Aβ-aggregation scores. With linear mixed models, we assessed whether Aβ-aggregation scores were predictive of cognitive functioning. Analyses were repeated in an early independent validation cohort of 383 Amyloid Imaging to Prevent Alzheimer's Disease Prognostic and Natural History Study individuals (224 [58.5%] females, mean age 65.2 ± 6.9 years).
Results: The imbalance model could be fit (pseudo- R 2 = 0.94) in both cohorts, across CSF kits and PET tracers. Although no associations were observed with the main methodological factors, lower Aβ-aggregation scores were associated with larger ventricular volume (β = 0.13, p < 0.001), male sex (β = -0.18, p = 0.019), and homozygous APOE -ε4 carriership (β = -0.56, p < 0.001), whereas higher scores were associated with increased uncorrected CSF p-tau (β = 0.17, p < 0.001) and t-tau (β = 0.16, p < 0.001), better baseline executive functioning (β = 0.12, p < 0.001), and slower global cognitive decline (β = 0.14, p = 0.006). In the validation cohort, we replicated the associations with APOE -ε4, CSF t-tau, and, although modestly, with cognition.
Discussion: We propose a novel continuous model of Aβ CSF/PET biomarker imbalance, accurately describing heterogeneity in soluble vs aggregated Aβ pools in 2 independent cohorts across the full Aβ continuum. Aβ-aggregation scores were consistently associated with genetic and AD-associated CSF biomarkers, possibly reflecting disease heterogeneity beyond methodological influences.
Databáze: MEDLINE
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