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Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology [electronic resource].

Published:
Bethesda, Md. : National Institutes of Health (U.S.), 2016.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
Physical Description:
pages 1,887-1,896 : digital, PDF file
Additional Creators:
Lawrence Berkeley National Laboratory, National Institutes of Health (U.S.), and United States. Department of Energy. Office of Scientific and Technical Information
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Summary:
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 Aβ42. 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 Aβ42. 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 rates of decline.
Report Numbers:
E 1.99:1379344
Subject(s):
Note:
Published through SciTech Connect.
04/15/2016.
"ark:/13030/qt1x79243g"
Neurology 86 20 ISSN 0028-3878 AM
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.
Funding Information:
AC02-05CH11231
View MARC record | catkey: 23492778