Journal article

Disruption of cholinergic neurotransmission exacerbates A beta-related cognitive impairment in preclinical Alzheimer's disease

Yen Ying Lim, Paul Maruff, Rachel Schindler, Brian R Ott, Stephen Salloway, Don C Yoo, Richard B Noto, Claudia Y Santos, Peter J Snyder

Neurobiology of Aging | ELSEVIER SCIENCE INC | Published : 2015

Abstract

Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in preclinical Alzheimer's disease (AD) and may be associated with abnormal beta-amyloid (Aβ) accumulation. Therefore, disruption of cholinergic neurotransmission with scopolamine may unmask otherwise undetectable cognitive deficits in preclinical AD. To compare the effects of low-dose (0.20 mg s.c.) scopolamine on cognition between Aβ+ and Aβ- cognitively normal (CN) older adults using the Groton Maze Learning Test (GMLT). CN older adults completed the GMLT predose and then received scopolamine (0.20 mg) subcutaneously. Participants were reassessed 1-, 3-, 5-, 7-, and 8-hours post dose. All particip..

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Funding Acknowledgements

This study was funded, in part, by an experimental medicine research grant to Peter J. Snyder from Pfizer Inc. Additional funding was provided by a gift from Ximedica Inc, to support the Clinical Research Center of the Lifespan Hospital System (Providence, RI). Neither Pfizer Inc., nor Ximedica Inc., had any role in the design or conduct of this study; and neither company had any role in the data analyses, interpretation, or writing of this report. The authors would like to thank Christine Getter for study coordination; Dr. Catherine Gordon and Dr. Gregory Jay for serving as medical monitors for the study; Kimberly Bixby for assisting with the recruitment of participants; Sarah Freelove, Gail Yates, and Barbara Bancroft for performing scopolamine injections. The authors also thank all those who participated in the study for their commitment and dedication to helping advance research into the early detection and causation of AD. Yen Ying Lim collected a majority of the data, provided logistical support throughout the trial, ran all statistical analyses, and prepared a first draft of this report; Paul Maruff co-developed the initial hypothesis, provided advice throughout the trial and co-authored this report; Rachel Schindler, Brian R. Ott, and Stephen Salloway all contributed to the study design and coauthored this report; Richard Noto and Don Yoo interpreted all positron emission tomography imaging results and co-authored this report; Peter J. Snyder formulated the initial hypothesis, designed the primary outcome measure (GMLT), authored the study protocol, led the study team, co-authored this report, and serves as senior author.