The effect of curcumin on age-related cognitive decline in the rhesus monkey

描述(由申请人提供)：流行病学研究支持这一发现，即早在人生的第五个十年就有认知能力下降的迹象，而且，估计的 65岁以上人群中更显著下降(MCI)的患病率在10%到20%之间。有几条证据表明，白质的变化是认知能力下降的神经基础，而认知能力下降可能是氧化应激和炎症的结果。因此，由于它们的抗炎和抗氧化作用，饮食多酚作为减缓、阻止甚至逆转与年龄相关的认知衰退的潜在候选者正受到认真的关注。对于这一不断演变的假说，姜黄素，一种天然的苯酚和生姜家族的成员，已经被证明有这样的积极作用，并提供了一个强有力的理论基础来继续这一假说，即姜黄素可能是一种有效的治疗干预年龄相关性认知下降的假说。因此，在这个项目中，我们将第一次在非人类灵长类动物模型中测试这样的假设，即化合物姜黄素(姜黄素)将通过直接适应于人类或应用于人类的行为任务来改变与年龄相关的认知下降的过程。此外，我们将使用已建立的和创新的MRI扫描方案来评估大脑完整性的变化，并使用免疫组织化学分析来量化受损髓鞘的组织病理学标记。结果衡量标准将根据三年期间和结束时认知表现的变化进行评估。据推测，与年龄匹配的对照组相比，接受姜黄素治疗的猴子将表现出较轻的髓鞘病变和变性，因此较少与年龄相关的认知障碍。

DESCRIPTION (provided by applicant): Epidemiologic studies support the finding that cognitive decline is evidenced as early as the fifth decade of life and further, that the estimated prevalence of more marked decline (MCI) for people over 65 years of age is between 10% and 20%. Several lines of evidence point to alterations in white matter as the neural basis of cognitive decline that, in turn, may be the consequence of oxidative stress and inflammation. As a result, by virtue of their anti-inflammatory and antioxidant effects, dietary polyphenols are gaining serious attention as potential candidates to slow, arrest, or perhaps even reverse, age-related cognitive decline. Toward this evolving hypothesis, Curcumin, a natural phenol and member of the ginger family, has been shown to evidence such positive effects and provide a strong rationale to pursue the hypothesis that Curcumin could be an effective therapeutic intervention in age-related cognitive decline. Accordingly, in this project, we will test, for the irst time in a non-human primate model, the hypothesis that the compound, Curcumin (Curcuma longa) will alter the course of age-related cognitive decline using behavioral tasks adapted directly from, or applied to, humans. In addition, we will use established and innovative MRI scanning protocols to assess changes in brain integrity and immunohistochemistry assays to quantify the histopathological markers of damaged myelin. Outcome measures will be assessed against changes in cognitive performance during and at the end of a three-year period. It is hypothesized that monkeys receiving Curcumin will evidence less severe myelin pathology and degeneration, and hence, less age-related cognitive impairment than age-matched controls.