Clinical trial of vestibular therapy to reduce falls in patients with Alzheimer's disease

项目总结 众所周知，阿尔茨海默病(AD)患者的平衡和步态障碍较大， 跌倒的比率相对于健康的老年人(60%-70%对30%)。目前，几乎没有有效的干预措施 存在管理和减轻AD跌倒的风险，不幸的是，跌倒仍然是AD的主要驱动因素之一 AD患者的发病率、制度化和死亡率。最近的研究表明，AD患者 前庭功能障碍的患病率(~50%)是年龄匹配的对照组(~25%)的两倍 流行率)。此外，在一项正在进行的观察性研究的试点数据中，我们已经表明，前庭 丢失与AD患者跌倒的比率增加有关。前庭疗法(VT)是一种久负盛名的 前庭缺失的治疗，包括以物理治疗为基础的练习，旨在促进 前庭功能减退的补偿。VT在改善平衡和降低跌倒风险方面是有效的 前庭功能受损的认知功能正常的患者。然而，VT能否有效地改善 前庭缺失的AD患者的平衡和减少跌倒的研究从未被探索过。在这项研究中，我们 建议对100例有前庭症状的轻中度AD患者进行VT的随机对照试验 减损。我们将以1：1的比例将患者随机分配到标准的VT疗程(每周1次，共8周)或 一种在努力和持续时间上相匹配的主动对照。我们将比较VT和主动控制的效果 主要是关于1年事故的下落率。我们还将调查VT之间潜在的中间结果 和跌倒--特别是平衡结果(VT的预测目标)和空间认知结果(一种新的 VT的靶点)-了解VT可能影响跌倒速度的潜在机制。我们假设 与主动控制相比，VT在降低1年事故跌倒发生率方面具有初步效果 对100例轻中度阿尔茨海默病患者进行方便抽样干预。我们还将探索是否 与主动控制干预相比，室性早搏在改善平衡和认知方面具有初步疗效。 为了完成这项拟议的研究，我们将从记忆和阿尔茨海默病患者中招募100名患者 治疗中心，约翰霍普金斯大学著名的AD临床研究资源。瀑布是一种 阿尔茨海默病患者的灾难性后果。如果在第三阶段多中心试验之后进行该试点试验 强有力的证据表明，VT在减少跌倒方面有好处，这种低风险的干预措施可能会得到广泛应用 由现有的劳动力和基础设施传播和实施，并产生大量、 AD临床实践的持续变化。

Project summary Patients with Alzheimer’s disease (AD) are known to have greater balance and gait impairment and double the rate of falls relative to healthy older adults (60-70% vs ~30%). Currently, few effective interventions exist to manage and mitigate falls in AD, and unfortunately, falls continue to be one of the primary drivers of morbidity, institutionalization, and mortality among AD patients. Recent studies have shown that AD patients have a two-fold higher prevalence of vestibular impairment (~50%) relative to age-matched controls (~25% prevalence). Additionally, in pilot data from an ongoing observational study, we have shown that vestibular loss is associated with an increased rate of falls in AD patients. Vestibular therapy (VT) is a well-established treatment for vestibular loss, and consists of physical therapy-based exercises designed to foster compensation for reduced vestibular function. VT is effective in improving balance and reducing fall risk in cognitively-intact patients with vestibular impairment. However, whether VT could be effective in improving balance and reducing falls in AD patients with vestibular loss has never been explored. In this study, we propose a randomized controlled trial of VT in 100 patients with mild-moderate AD who have vestibular impairment. We will randomize patients 1:1 to a standard course of VT (1 session per week for 8 weeks) or to an active control matched for effort and duration. We will compare the efficacy of VT vs. active control primarily on 1-year incident fall rate. We will also investigate potential intermediate outcomes between VT and falls – specifically balance outcomes (a predicted target of VT) and spatial cognitive outcomes (a novel target of VT) – to understand potential mechanisms by which VT may influence fall rates. We hypothesize that VT will have preliminary efficacy in reducing 1-year incident fall rates relative to an active control intervention in a convenience sample of 100 patients with mild-moderate AD. We will also explore whether VT has preliminary efficacy in improving balance and cognition relative to the active control intervention. To accomplish the proposed study, we will recruit 100 patients from the Memory and Alzheimer’s Treatment Center, a well-established AD clinical research resource at Johns Hopkins. Falls are a disastrous outcome in patients with AD. If this pilot trial followed by a Phase III multi-center trial provide strong evidence for the benefit of VT in reducing falls, this low-risk intervention could be widely disseminated and implemented by an existing workforce and infrastructure, and produce substantial, sustained change in AD clinical practice.