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

Artikel i vetenskaplig tidskrift
Författare P. S. Insel
N. Mattsson
R. S. Mackin
Michael Schöll
R. L. Nosheny
D. Tosun
M. C. Donohue
P. S. Aisen
W. J. Jagust
M. W. Weiner
Publicerad i Neurology
Volym 86
Nummer/häfte 20
Sidor 1887-1896
ISSN 0028-3878
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 1887-1896
Språk en
Länkar dx.doi.org/10.1212/WNL.000000000000...
Ämneskategorier Neurologi, Geriatrik, Reumatologi och inflammation

Sammanfattning

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. © 2016 American Academy of Neurology.

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