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

Alzheimer’s Research & Therapy

Danielle Goldfarb¹  Alex Song²  Paul Maruff³  Peter J. Snyder⁴  Jessica Alber⁴  Cláudia Y. Santos⁴  Louisa I. Thompson⁵  Brian R. Ott⁵  Stephen P. Salloway⁵  Don C. Yoo⁶  Richard B. Noto⁶  Edmund Arthur⁷ 

[1] Banner Alzheimer’s Institute;Brown University;Cogstate Ltd.;Department of Biological & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island;Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University;Department of Radiology, Warren Alpert Medical School of Brown University;Ryan Institute for Neuroscience, University of Rhode Island;

关键词: Alzheimer disease;    Preclinical Alzheimer’s disease;    Early detection;    Cholinergic;    Cognition;    Biomarkers;   

DOI  :  10.1186/s13195-020-00599-1

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown