Cocoa Supplement and Multivitamin Outcomes Study in the Mind (COSMOS-Mind)

 描述（由申请人提供）：确定一种安全，负担得起的，耐受性良好的干预措施，防止老年人认知功能下降是至关重要的公共卫生。基础科学和小型临床研究有令人信服的证据表明，可可黄烷醇可以保护老年人的认知功能，降低阿尔茨海默病（AD）和相关痴呆症的风险。因此，这种干预措施可能对老年人的医疗保健利用和成本、护理人员负担和整体生活质量产生重要的下游效益。然而，可可黄烷醇对认知的影响需要在确定的临床试验中进行评估。我们建议利用受资助的可可补充剂和多种维生素结局研究（COSMOS）提供的独特而及时的机会，进行一项辅助认知研究，称为“COSMOS-Mind”。“COSMOS是一项随机、双盲、安慰剂对照的临床试验，将于2016年初开始随机化。它将在全国范围内招募18，000名女性和男性，来自妇女健康倡议（WHI）参与者队列和维生素D和OmegA- 3 TriaL（VITAL）非随机应答队列，并将主要通过邮件进行。COSMOS将评估高效可可黄烷醇提取物（含有750 mg/d黄烷醇的胶囊，包括75 mg（-）-表儿茶素和90 mg可可碱; Mars Symbioscience）和多种维生素（辉瑞Centrum（r）银（r））-单独或组合-是否会在4年的随访中降低心血管疾病和癌症的风险。COSMOS领导层邀请我们进行一项辅助研究，以检查其干预措施的认知效果，因为我们在地理位置多样化的WHI队列中使用具有成本效益和经验证的电话管理评估收集认知数据方面拥有广泛而成功的经验。COSMOS-Mind将从COSMOS招募2,000名参与者（50%男性，年龄≥65岁），并在随机化前和每年进行一次标准化电话认知评估，持续3年，以检查可可黄烷醇对认知复合结局的纵向影响。我们还将确定服用多种维生素是否有益于认知，探索可可黄烷醇是否降低痴呆症（包括AD）的风险，并检查对关键认知领域（例如，执行功能、短期记忆）。我们的评估将产生可靠和敏感的记忆，执行功能，语言和整体认知功能的措施。我们将使用我们以前成功的技术，以促进高保留率和纵向可靠性。我们提出的队列将提供>90%的统计功效来确定可可黄烷醇是否保护认知功能。我们将与COSMOS研究小组，WHI和VITAL分享我们的数据，以促进其他研究并扩大我们研究的科学足迹。COSMOS-Mind是一个前所未有的，具有成本效益的，及时的机会来测试可可黄烷醇-一种有前途的和广泛可翻译的干预-是否可以防止正常和病理性认知下降。

 DESCRIPTION (provided by applicant): Identifying a safe, affordable, and well-tolerated intervention that prevents cognitive decline in older adults is of critical public health importanc. There is compelling evidence from basic science, and small clinical studies that cocoa flavanols may protect cognitive function in older adults and reduce risk of Alzheimer's disease (AD) and related dementia. Thus, this intervention could have important downstream benefits for health care utilization and cost, caregiver burden, and overall quality of life for older adults. Cocoa flavanol effects on cognition, however, need to be assessed in a definitive clinical trial. We propose to leverage the unique and timely opportunity provided by the funded COcoa Supplement and Multivitamin Outcomes Study (COSMOS) to conduct an ancillary cognitive study, referred to as "COSMOS-Mind." COSMOS is a randomized, double-blind, placebo-controlled clinical trial that will begin randomization in early 2016. It will enroll 18,000 women and men nationwide, drawn from the Women's Health Initiative (WHI) participant cohort and the VITamin D and OmegA- 3 TriaL (VITAL) non-randomized respondent cohort, and will be conducted primarily by mail. COSMOS will assess whether high-potency cocoa flavanol extract (capsules containing 750 mg/d flavanols, including 75 mg (-)-epicatechin, and 90 mg theobromine; Mars Symbioscience) and a multivitamin (Pfizer Centrum(r) Silver(r)) - alone or in combination - will reduce risk of cardiovascular disease and cancer over 4 years of follow-up. The COSMOS leadership invited us to conduct an ancillary study to examine the cognitive effects of their interventions, given our extensive and successful experience collecting cognitive data using cost-effective and validated telephone-administered assessments in the geographically diverse WHI cohort. COSMOS-Mind will enroll 2,000 participants from COSMOS (50% men, aged ≥65 years), and conduct standardized telephone cognitive assessments pre-randomization and annually for 3 years to examine longitudinal effects of cocoa flavanols on a cognitive composite outcome. We will also establish whether administration of a multivitamin benefits cognition, explore whether cocoa flavanols reduce risk of dementia including AD, and examine intervention effects on key cognitive domains (e.g., executive function, short-term memory). Our assessments will yield reliable and sensitive measures of memory, executive function, language, and global cognitive function. We will use our previously successful techniques to promote high retention and longitudinal reliability. Our proposed cohort will provide >90% statistical power to establish whether cocoa flavanols protect cognitive function. We will share our data with the COSMOS study groups, WHI, and VITAL to facilitate other investigations and expand the scientific footprint of our study. COSMOS-Mind is an unprecedented, cost- efficient, and timely opportunity to test whether cocoa flavanols - a promising and widely translatable intervention - can protect against normal and pathological cognitive decline.