ACE trial design: Equol targeting estrogen receptor-β in vascular and cognitive aging

IF 6.8 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-08-18 DOI:10.1002/trc2.70144

Akira Sekikawa, Whitney Wharton, Cristina Murray-Krezan, Minjie Wu, Yuefang Chang, Beth E. Snitz, Mindy Coccari, Shaolin Yang, Monica L. Love, Deborah Cusick, Rongrong Wang, Mengyi Li, Chloe Park, Jiatong Li, Theodore M. DeConne, Carrie Smith, Danielle D. Verble, Michelle Quallich Lancet, Tatiana Foroud, Tae Kim, Neelesh K. Nadkarni, Joseph M. Mettenburg, Ezequiel Zamora, Oscar L. Lopez, Timothy M. Hughes

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引用次数: 0

Abstract

INTRODUCTION

Equol, a gut microbiome-derived metabolite of soy isoflavone daidzein, functions as a selective estrogen receptor beta (ERβ) agonist. In preclinical studies, it has demonstrated vascular protective and antioxidant effects, with emerging evidence suggesting potential neuroprotective properties. However, its role in preventing vascular aging and cognitive decline in humans remains unexplored. The Arterial Stiffness, Cognition, and Equol (ACE) trial investigates whether daily equol supplementation can slow the progression of arterial stiffness, brain white matter lesions, and cognitive decline in older adults without dementia.

METHODS

ACE is a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted at the University of Pittsburgh, Wake Forest University, and Emory University. Community-dwelling adults aged 65 to 85 years without dementia were enrolled and randomized 1:1 to receive either 10 mg/day of equol or placebo for 24 months. The primary outcome is arterial stiffness assessed by carotid-femoral pulse wave velocity. Secondary outcomes include white matter lesions detected on the brain magnetic resonance imaging and cognitive function as assessed by the Preclinical Alzheimer Cognitive Composite. Power calculations were based on a planned sample size of 400 participants, accounting for an anticipated 20% attrition rate.

RESULTS

A total of 1783 individuals were pre-screened, and 764 underwent in-person eligibility assessment. Of these, 369 participants were randomized into two groups: Arm A (n = 185) and Arm B (n = 184). The randomized sample self-reported as 52% women and 22% Black/African American participants. Baseline demographic and clinical characteristics were well balanced between the two arms, indicating successful randomization.

DISCUSSION

ACE successfully enrolled a racially diverse population of older adults and achieved near-target recruitment. ACE is the first large-scale trial to evaluate whether equol, a selective ERβ agonist, can impact vascular and cognitive aging, paving the way for precision nutrition strategies in dementia prevention.

Highlights

We detail the first randomized controlled trial of equol, an estrogen receptor beta (ERβ) agonist, for vascular and cognitive aging.
The study tested equol's effects on arterial stiffness, white matter lesions, and cognition.
The multisite trial enrolled 369 self-reported White and Black older adults aged 65 to 85 years.
The trial investigated a novel dietary metabolite targeting ERβ pathways.

Abstract Image

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ACE试验设计：马雌酚靶向血管和认知衰老中的雌激素受体-β

马酚是一种肠道微生物衍生的大豆异黄酮大豆苷元代谢物，是一种选择性雌激素受体β (ERβ)激动剂。在临床前研究中，它已显示出血管保护和抗氧化作用，新出现的证据表明它具有潜在的神经保护作用。然而，它在预防血管老化和人类认知能力下降方面的作用仍未被探索。动脉僵硬、认知和马酚（ACE）试验研究了每日补充马酚是否可以减缓无痴呆老年人动脉僵硬、脑白质病变和认知能力下降的进展。ACE是一项多中心、随机、双盲、安慰剂对照的临床试验，在匹兹堡大学、维克森林大学和埃默里大学进行。在社区居住的65 - 85岁无痴呆的成年人被招募，并按1:1的比例随机分配，接受10毫克/天的马雌酚或安慰剂治疗24个月。主要结果是动脉僵硬度通过颈-股脉波速度评估。次要结果包括脑磁共振成像检测到的白质病变和临床前阿尔茨海默认知复合评估的认知功能。权力计算是基于400名参与者的计划样本量，预计流失率为20%。结果：共有1783人被预筛选，764人接受了亲自资格评估。其中，369名参与者随机分为两组：A组（n = 185）和B组（n = 184）。随机抽样的参与者中，女性占52%，黑人/非裔美国人占22%。基线人口统计学和临床特征在两组之间很好地平衡，表明成功的随机化。ACE成功招募了不同种族的老年人，并达到了接近目标的招募。ACE是首个评估选择性ERβ激动剂马雌酚是否影响血管和认知衰老的大规模试验，为精准营养策略预防痴呆铺平了道路。我们详细介绍了第一项随机对照试验，雌马酚，雌激素受体β (ERβ)激动剂，血管和认知衰老。该研究测试了马酚对动脉硬化、白质病变和认知的影响。这项多地点试验招募了369名年龄在65至85岁之间的自我报告的白人和黑人老年人。该试验研究了一种靶向ERβ通路的新型膳食代谢物。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.