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，即认知能力下降早在生命的第50个十年就已证明，而且， 65岁以上人群的MCI患病率在10%至20%之间。几条证据表明，白色物质的改变是认知能力下降的神经基础，而认知能力下降又可能是氧化应激和炎症的结果。因此，凭借其抗炎和抗氧化作用，膳食多酚作为减缓、阻止甚至逆转与年龄相关的认知能力下降的潜在候选者正受到严重关注。对于这一不断发展的假设，姜黄素，一种天然苯酚和生姜家族的成员，已被证明证明具有这种积极作用，并为追求姜黄素可能是与年龄相关的认知能力下降的有效治疗干预的假设提供了强有力的理由。因此，在这个项目中，我们将在非人类灵长类动物模型中首次测试这一假设，即化合物姜黄素（Curcuma longa）将使用直接从人类适应或应用于人类的行为任务来改变与年龄相关的认知衰退的过程。此外，我们将使用既定和创新的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测定来量化受损髓鞘的组织病理学标记物。将根据三年期间和结束时认知表现的变化评估结果指标。假设接受姜黄素的猴子将表现出较不严重的髓鞘病理和变性，因此，与年龄匹配的对照相比，与年龄相关的认知障碍较少。

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.