Department of Neurology, Alpert Medical School, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital, Providence, RI, USA.
Department of Neurology, Alpert Medical School, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital, Providence, RI, USA.
Alzheimers Dement. 2014 Mar;10(2):262-7. doi: 10.1016/j.jalz.2014.01.009.
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."
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.
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.
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.
在阿尔茨海默病（AD）的早期阶段，异常的β-淀粉样蛋白（Aβ）与中枢乙酰胆碱能张力的有害变化有关，这种变化可能会被胆碱能拮抗剂所揭示。我们旨在确定一种最佳的“微剂量”东莨菪碱，以开发一种“认知应激测试”。
有 2 个 AD 风险因素，但皮质 Aβ负担较低的健康老年人（n=26，年龄 55-75 岁），在基线时完成格罗顿迷宫学习测试（GMLT），然后接受东莨菪碱（0.20mg 皮下注射）。参与者在注射后 1、3、5、7 和 8 小时接受重新评估。
在总错误、规则破坏错误和 GMLT 综合方面，基线和注射后 3 小时之间的表现存在显著差异，差异程度中等（d≈0.50），且与体重无关。
非常低剂量的东莨菪碱在 3 小时后（Tmax）会导致可靠的认知障碍，并且在 5 小时内完全恢复认知，支持其作为一种预测性测试范式，以识别具有潜在临床前 AD 的个体。该范式正在更大的健康成年人队列中实施，这些成年人的 Aβ 水平较高或较低，以识别组间的药效学差异。
