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组合鸡尾酒可改善人类衰老和阿尔茨海默病犬模型的空间注意力。

A combination cocktail improves spatial attention in a canine model of human aging and Alzheimer's disease.

机构信息

Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.

出版信息

J Alzheimers Dis. 2012;32(4):1029-42. doi: 10.3233/JAD-2012-120937.

Abstract

Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of amyloid-β (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t11 = 4.3, p = 0.001) and were more accurate across all distances (F(1,9) = 20.7, p = 0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and cerebrospinal fluid Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD.

摘要

阿尔茨海默病(AD)涉及大脑中的多种病理过程,包括炎症和氧化损伤增加,以及淀粉样β(Aβ)斑块的积累。我们假设针对这些多种途径的组合治疗方法可能为 AD 患者提供认知和神经病理学益处。为了验证这一假设,我们使用了一种犬类人类衰老和 AD 模型。老年犬自然会出现学习和记忆障碍、人类类型的 Aβ 沉积和大脑中的氧化损伤。因此,9 只老年比格犬(98-115 个月)接受了一种含有(1)姜黄提取物,含有 95%姜黄素;(2)绿茶提取物,含有 50%表没食子儿茶素没食子酸酯;(3)N-乙酰半胱氨酸;(4)R-α 硫辛酸;和(5)黑胡椒提取物,含有 95%胡椒碱的医疗食品鸡尾酒的治疗。9 只年龄相似的狗作为安慰剂治疗对照组。治疗 3 个月后,13 只狗完成了一项可变距离地标任务,用作空间注意力的测量。与安慰剂治疗动物相比,接受医疗食品鸡尾酒的狗的错误分数明显更低(t11 = 4.3,p = 0.001),在所有距离上都更准确(F(1,9)= 20.7,p = 0.001),表明空间注意力整体提高。视觉辨别学习、执行功能和空间记忆的测量以及大脑和脑脊液 Aβ 的水平不受鸡尾酒的影响。我们的结果表明,这种医疗食品鸡尾酒可能有益于改善与认知障碍相关的空间注意力和动机缺陷。

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