Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

Philip S Insel; Niklas Mattsson; R Scott Mackin; Michael Schöll; Rachel L Nosheny; Duygu Tosun; Michael C Donohue; Paul S Aisen; William J Jagust; Michael W Weiner; Alzheimer's Disease Neuroimaging Initiative

doi:10.1212/WNL.0000000000002683

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Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

Journal article

Open access

Peer reviewed

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

Philip S Insel, Niklas Mattsson, R Scott Mackin, Michael Schöll, Rachel L Nosheny, Duygu Tosun, Michael C Donohue, Paul S Aisen, William J Jagust, Michael W Weiner, …

Neurology, Vol.86(20), pp.1887-1896

05/17/2016

DOI: 10.1212/WNL.0000000000002683

PMCID: PMC4873684

PMID: 27164667

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Abstract

To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.

Magnetic Resonance Imaging

Brain - diagnostic imaging

Aniline Compounds

Humans

Male

Cognition

Positron-Emission Tomography

Atrophy

Brain - metabolism

Ethylene Glycols

Amyloid beta-Peptides - cerebrospinal fluid

Cognitive Dysfunction - psychology

Mental Status Schedule

Female

Cognitive Dysfunction - diagnostic imaging

Radiopharmaceuticals

Peptide Fragments - cerebrospinal fluid

Cognitive Dysfunction - cerebrospinal fluid

Disease Progression

Neuropsychological Tests

Regression Analysis

Fluorodeoxyglucose F18

Aged

Biomarkers - cerebrospinal fluid

Longitudinal Studies

Details

Title: Subtitle: Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology
Creators: Philip S Insel - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA. philipinsel@gmail.com
Niklas Mattsson - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
R Scott Mackin - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Michael Schöll - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Rachel L Nosheny - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Duygu Tosun - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Michael C Donohue - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Paul S Aisen - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
William J Jagust - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Michael W Weiner - From the Center for Imaging of Neurodegenerative Diseases (P.S.I., R.S.M., R.L.N., D.T., M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; Departments of Radiology and Biomedical Imaging (P.S.I., D.T., M.W.W.) and Psychiatry (R.S.M.), University of California, San Francisco; Clinical Memory Research Unit, Faculty of Medicine (P.S.I., N.M.), Lund University; Memory Clinic (N.M.) and Department of Neurology (N.M.), Skåne University Hospital, Lund University; MedTech West and the Department of Clinical Neuroscience and Rehabilitation (M.S.), University of Gothenburg, Sweden; Department of Neurology (M.C.D., P.S.A.), Keck School of Medicine, University of Southern California, Los Angeles; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; and Life Sciences Division (M.S., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley CA
Alzheimer's Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Neurology, Vol.86(20), pp.1887-1896
DOI: 10.1212/WNL.0000000000002683
PMID: 27164667
PMCID: PMC4873684
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: United States
Grant note: P50 AG005142 / NIA NIH HHS K08 MH081065 / NIMH NIH HHS CIHR U01 AG010483 / NIA NIH HHS U24 AG021886 / NIA NIH HHS P30 AG013846 / NIA NIH HHS P30 AG010129 / NIA NIH HHS U01 AG024904 / NIA NIH HHS R01 AG016381 / NIA NIH HHS R01 AG030048 / NIA NIH HHS K01 AG030514 / NIA NIH HHS
Language: English
Date published: 05/17/2016
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051585502771

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