Microdosing of scopolamine as a "cognitive stress test": Rationale and test of a very low dose in an at‐risk cohort of older adults. Issue 2 (1st March 2014)

• Record Type: Journal Article
• Authors: Snyder, Peter J.; Lim, Yen Ying; Schindler, Rachel; Ott, Brian R.; Salloway, Stephen; Daiello, Lori; Getter, Christine; Gordon, Catherine M.; Maruff, Paul
• Is Part Of: Alzheimer's & dementia. Volume 10:Issue 2(2014)
• Page Start: 262
• Page End: 267
• Publication Date: 2014-03-01
• Subjects: Alzheimer disease -- Preclinical Alzheimer's disease -- Early detection -- Cholinergic -- Cognition -- Biomarkers -- Diagnosis -- Anticholinergic drugs -- Scopolamine -- β‐Amyloid protein; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2014.01.009
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Abnormal β‐amyloid (Aβ) is associated with deleterious changes in central acetylcholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist. We aimed to establish an optimal "microdose" of scopolamine for the development of a "cognitive stress test." Methods: Healthy older adults ( n = 26, aged 55–75 years) with two risk factors for AD, but with low cortical Aβ burden, completed the Groton Maze Learning Test (GMLT) at baseline and then received scopolamine (0.20 mg subcutaneously). Participants were reassessed at 1, 3, 5, 7, and 8 hours postinjection. Results: There were significant differences, of a moderate magnitude, in performance between baseline and 3 hours postinjection for total errors, rule break errors, and the GMLT composite ( d ≈ 0.50) that were all unrelated to body mass. Conclusions: A very low dose of scopolamine leads to reliable cognitive impairment at 3 hours postdose (Tmax ) and full cognitive recovery within 5 hours, supporting its use as a prognostic test paradigm to identify individuals with potential preclinical AD. This paradigm is being implemented in a larger cohort of healthy adults, with high or low Aβ, to identify pharmacodynamic differences between groups.