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

Insel, Philip S. LU ; Mattsson, Niklas LU ; Mackin, R. Scott; Schöll, Michael LU ; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J. and Weiner, Michael W. (2016) In Neurology 86(20). p.1887-1896
Abstract

Objective: 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... (More)

Objective: 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. 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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
86
issue
20
pages
10 pages
publisher
American Academy of Neurology
external identifiers
  • Scopus:84969242548
ISSN
0028-3878
DOI
10.1212/WNL.0000000000002683
language
English
LU publication?
yes
id
82185191-8ddd-4140-8b3b-c40e015449ae
date added to LUP
2016-05-31 15:31:15
date last changed
2016-10-23 04:43:38
@misc{82185191-8ddd-4140-8b3b-c40e015449ae,
  abstract     = {<p>Objective: 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. 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.</p>},
  author       = {Insel, Philip S. and Mattsson, Niklas and Mackin, R. Scott and Schöll, Michael and Nosheny, Rachel L. and Tosun, Duygu and Donohue, Michael C. and Aisen, Paul S. and Jagust, William J. and Weiner, Michael W.},
  issn         = {0028-3878},
  language     = {eng},
  month        = {05},
  number       = {20},
  pages        = {1887--1896},
  publisher    = {ARRAY(0x8bc8898)},
  series       = {Neurology},
  title        = {Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000002683},
  volume       = {86},
  year         = {2016},
}