کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6803842 | 1433551 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disruption of cholinergic neurotransmission exacerbates Aβ-related cognitive impairment in preclinical Alzheimer's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
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 Aβâ 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 participants underwent positron emission tomography neuroimaging for Aβ using 18F-florbetapir within 6 weeks of their baseline visit. Rhode Island Hospital Clinical Research Center, Providence, USA. CN older adults (n = 63), with a family history of AD and subjective memory complaints were enrolled (15 were classified as Aβ+ and 48 were classified as Aβâ). Cognition was assessed using the computerized GMLT at all predose and post-dose time points. At 5-hours post dose, the Aβ+ group performed significantly worse than the Aβâ group on all measures of learning efficiency and working memory and/or executive function (Cohen's d = 1.13-1.56). When participants were classified as having an abnormal response to scopolamine (based on change score at 5-hours post dose >0), 100% were correctly classified as Aβ+ and 67% as Aβâ. The results of this study suggest that diminished cholinergic tone likely occurs in preclinical AD, and as such, the use of a cholinergic stress test to perturb an already compromised neurotransmitter system may be an effective way of identifying CN older adults who are in this preclinical stage of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 36, Issue 10, October 2015, Pages 2709-2715
Journal: Neurobiology of Aging - Volume 36, Issue 10, October 2015, Pages 2709-2715
نویسندگان
Yen Ying Lim, Paul Maruff, Rachel Schindler, Brian R. Ott, Stephen Salloway, Don C. Yoo, Richard B. Noto, Cláudia Y. Santos, Peter J. Snyder,