Arterial Stiffness, Cognition, and Equol (ACE)

动脉僵硬度、认知和雌马酚 (ACE)

• 批准号: 10570886
• 负责人: AKIRA SEKIKAWA
• 金额: $ 313.39万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570886
• 关键词: Academy; Address; Affect; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Amyloid beta-42; Amyloid beta-Protein; Biological; Biological Markers; Blood; Brain; Carotid Atherosclerotic Disease; Cerebrovascular Circulation; Cognition; Cognitive; Collagen; Control Groups; Cross-Sectional Studies; Data; Dementia; Diet; Elastases; Elderly; Goals; Health; Hypertension; Impaired cognition; Individual; Intervention; Investigation; Isoflavones; Japan; Japanese; Knowledge; Lead; Lesion; Link; Measures; Medicine; Nutrient; Observational Study; Outcome; Participant; Pathology; Phenotype; Placebos; Plasma; Precision Health; Property; Public Health; Randomized; Randomized, Controlled Trials; Recommendation; Reporting; Research; Risk Factors; Risk Reduction; Role; Sampling; Serum; Signal Transduction; Site; Smooth Muscle Myocytes; Structure; Subgroup; Supplementation; Testing; Therapeutic; Time; Vascular Smooth Muscle; Vascular calcification; Venous; Woman; age related; aged; arterial stiffness; brain volume; cerebrovascular; cognitive benefits; cognitive function; comparison control; cost; crosslink; daidzein; design; early phase trial; equol; gut microbiome; imaging study; improved; inhibitor; microbiome; middle age; mild cognitive impairment; phase III trial; pre-clinical; preclinical study; prevent; primary outcome; recruit; secondary outcome; soy; soy protein isolate; tau-1; therapeutic target; trend; trial design; white matter

Project Summary/Abstract This application, “Arterial stiffness, Cognition and Equol (ACE),” is an early stage randomized controlled trial (RCT) designed to test the effect of a 24-month intervention of 10 mg/day equol supplementation on cognitive decline, arterial stiffness, and white matter lesions (WMLs) among 400 individuals aged 70+ without dementia. Recent studies in Japan reported that a diet high in soy and soy isoflavones (ISFs) is inversely associated with incident cognitive impairment and dementia. The Women’s Isoflavone Soy Health (WISH) in the US, an RCT of ISFs, however, showed no significant effect of ISFs on cognition. We posit that the discrepant result is due to the difference in equol-producing capability. Equol, a metabolite of an ISF daidzein transformed by the gut microbiome, is most bioactive among all ISFs and their metabolites. 50-70% of Japanese convert daidzein to equol in contrast to 20-30% of Americans. The subgroup analysis of WISH showed that equol producers had better cognition than the control group, suggesting that equol may slow cognitive decline. In addition, arterial stiffness, a significant predictor of cognitive decline, is significantly improved in a short-duration RCT of 10 mg/day equol supplementation in middle-aged subjects. Finally, WMLs are a risk factor for age-related cognitive decline and dementia. We reported a longitudinal association of equol-producing status with WML% (WML volume normalized to total brain volume) in cognitively normal elderly in Japan. Serum equol levels were measured using samples collected and stored 6-9 years before the imaging study; 50% were non-equol producers and equol producers were divided into two groups (high and low). Non-equol producers had >100% greater WML% than high producers, suggesting that supplementation of equol may slow the progression of WMLs. No previous study has tested the effect of equol supplementation on cognitive decline, arterial stiffness or WMLs in older adults. We hypothesize that supplementation of 10 mg/day equol will significantly slows both cognitive decline (primary outcome), and the progression of arterial stiffness and WML% (secondary outcomes). The overall impact of our trial will be to determine the role of equol supplementation in improving cognitive and cerebrovascular outcomes in older adults. Should a positive signal be identified in this early-stage trial, it would not only lead to a phase 3 trial to test a hypothesis that equol supplementation reduces risk for cognitive impairment and dementia but also to an RCT of a diet rich in ISFs between equol producers and non-producers, moving toward a precision health strategy.

项目摘要/摘要 这项名为“动脉僵硬、认知和平衡(ACE)”的应用是一项早期随机对照试验 (RCT)旨在测试为期24个月的干预对认知能力的影响，每天补充10毫克的马儿 在400名70岁以上的非痴呆症患者中，研究对象包括脑萎缩、动脉僵硬和脑白质损害(WML)。 日本最近的一项研究报告称，富含大豆和大豆异黄酮(ISF)的饮食与 偶发认知损害和痴呆。美国妇女大豆异黄酮类健康(WISH)的RCT 然而，ISF对认知没有显著的影响。我们假设不一致的结果是由于 马匹生产能力的差异。Quol，肠道转化的ISF大豆苷元的代谢物 微生物组是所有ISF及其代谢物中生物活性最强的。50%-70%的日本人将大豆苷元转化为 相比之下，美国人的比例为20%-30%。Wish的亚群分析表明，马儿生产者有 认知能力比对照组更好，这表明马兜铃可能会延缓认知能力的下降。此外，动脉 僵硬是认知衰退的一个重要预测指标，在10分的短期随机对照试验中显著改善 中年受试者每日补充等量镁。最后，WML是与年龄相关的风险因素 认知功能衰退和痴呆症。我们报告了马儿产生状态与WML%的纵向关联。 (WML体积归一化为总脑体积)在日本认知正常的老年人。血清等量水平 使用在影像研究前6-9年收集和储存的样本进行测量；50%为非等量样本 生产者和马匹生产者被分为两组(高和低)。非平分生产商有 &gt；比高产者高100%的WML%，这表明补充马兜铃醇可能会减缓 WMLs的进展。之前没有研究测试过补充马兜铃醇对认知能力下降的影响， 老年人的动脉僵硬或WMLs。我们假设每天补充10毫克的马赛克将会 显著减缓认知衰退(主要结果)和动脉僵硬的进展和 WML%(二次转归)。我们试验的总体影响将是确定Equol的作用 补充在改善老年人认知和脑血管结果中的作用。是否应该发出积极的信号 在这项早期试验中被确定，它不仅会导致第三阶段试验来测试等量的假设 补充降低认知障碍和痴呆症的风险，但对富含胰岛素样生长因子的饮食的RCT也是如此 在马匹生产国和非生产国之间，走向精准的健康战略。