Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aβ-related cognitive impairment in preclinical Alzheimer's disease after a 27-month delay interval.

Autor: Alber J; Department of Biological & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 75 Lower College Road, 2nd Floor, Kingston, RI, USA.; Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA.; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA., Maruff P; Cogstate Ltd., Melbourne, Victoria, Australia.; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia., Santos CY; Department of Biological & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 75 Lower College Road, 2nd Floor, Kingston, RI, USA., Ott BR; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA.; Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA., Salloway SP; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA.; Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA., Yoo DC; Department of Radiology, Warren Alpert Medical School of Brown University, Providence, RI, USA., Noto RB; Department of Radiology, Warren Alpert Medical School of Brown University, Providence, RI, USA., Thompson LI; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA., Goldfarb D; Banner Alzheimer's Institute, Phoenix, AZ, USA., Arthur E; Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA., Song A; Brown University, Providence, RI, USA., Snyder PJ; Department of Biological & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 75 Lower College Road, 2nd Floor, Kingston, RI, USA. pjsnyder@uri.edu.; Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA. pjsnyder@uri.edu.
Jazyk: angličtina
Zdroj: Alzheimer's research & therapy [Alzheimers Res Ther] 2020 Mar 24; Vol. 12 (1), pp. 31. Date of Electronic Publication: 2020 Mar 24.
DOI: 10.1186/s13195-020-00599-1
Abstrakt: Background: Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1-4, 2017). Previously, we established the scopolamine challenge test (SCT) as a "cognitive stress test" screening measure to identify individuals at risk for AD (Alzheimer's & Dementia 10(2):262-7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval.
Methods: Older adults (N = 63, aged 55-75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam.
Results: Significant differences in both cognitive performance and in Aβ neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period.
Conclusions: Cognitive response to the SCT (Alzheimer's & Dementia 10(2):262-7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years.
Databáze: MEDLINE
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