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

姜黄素对恒河猴年龄相关认知能力下降的影响

• 批准号: 8720659
• 负责人: Mark Barry Moss
• 金额: $ 60.93万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8720659
• 关键词: Affect; Age; Age-Years; Age-associated memory impairment; Aging; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antioxidants; Attention; Autopsy; Behavioral; Biological Assay; Brain; Carbon Dioxide; Cardiovascular Diseases; Cognition; Cognitive; Confocal Microscopy; Curcuma longa; Curcumin; Dementia; Densitometry; Dietary Intervention; Dietary Polyphenol; Diffusion; Disease; Employee Strikes; Epidemiologic Studies; Family; Female; Ginger; Human; Image; Immunofluorescence Microscopy; Immunohistochemistry; Impaired cognition; Individual; Inflammation; Intervention; Intervention Studies; Ischemic Stroke; Label; Learning; Life; Lipids; MRI Scans; Macaca mulatta; Malignant Neoplasms; Memory; Microglia; Modeling; Monkeys; Myelin; Neurodegenerative Disorders; New England; Organ; Outcome; Outcome Measure; Oxidative Stress; Pathology; Performance; Phenols; Predisposition; Prevalence; Primates; Process; Property; Prosencephalon; Protocols documentation; Research Personnel; Rest; Scanning; Short-Term Memory; Spices; Testing; Therapeutic; Therapeutic Intervention; Time; Tumeric; Venous; Veterinarians; Weight; Work; age effect; age related; anti aging; base; brain tissue; cognitive change; executive function; innovation; member; middle age; mild cognitive impairment; mind control; morphometry; nonhuman primate; normal aging; oxidation; public health relevance; relating to nervous system; white matter

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.

描述（由申请人提供）：流行病学研究支持这一发现，即早在 50 岁的时候就出现了认知能力下降，而且据估计 65 岁以上人群的更显着衰退 (MCI) 患病率在 10% 至 20% 之间。多项证据表明，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衰退的潜在候选者而受到广泛关注。针对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）已被证明具有这种积极作用，并为追求姜黄素可能成为与年龄相关的认知衰退的有效治疗干预措施的假设提供了强有力的理由。因此，在这个项目中，我们将首次在非人类灵长类动物模型中测试这一假设，即化合物姜黄素（Curcuma longa）将使用直接适应或应用于人类的行为任务来改变与年龄相关的认知能力下降的过程。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磷脂的组织病理学标记。结果测量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，接受姜黄素的猴子将表现出较不严重的髓磷脂病理和变性，因此与年龄匹配的对照组相比，与年龄相关的认知障碍较少。