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

Objective: Our objective is 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. Methods: 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 Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: 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. Conclusions: 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 Aβ 42. Lastly, 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 ratesmore » of decline.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [7] ;  [8] ;  [6]
  1. Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Departments of Radiology and Biomedical Imaging; Lund Univ. (Sweden). Clinical Memory Research Unit, Faculty of Medicine
  2. Lund Univ. (Sweden). Clinical Memory Research Unit, Faculty of Medicine; Skane University Hospital (Sweden). Department of Neurology
  3. Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Dept. of Psychiatry
  4. University of Gothenburg (Sweden). MedTech West and the Department of Clinical Neuroscience and Rehabilitation; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
  5. Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center
  6. Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Departments of Radiology and Biomedical Imaging
  7. University of Southern California, Los Angeles, CA (United States). Department of Neurology, Keck School of Medicine
  8. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Institute; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Accepted Manuscript
Journal Name:
Neurology
Additional Journal Information:
Journal Volume: 86; Journal Issue: 20; Journal ID: ISSN 0028-3878
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE: National Institutes of Health (NIH)
Contributing Orgs:
For the Alzheimer's Disease Neuroimaging Initiative
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1379344