Hyperbaric oxygen therapy for cognition in diabetic elderly at high dementia risk

高压氧治疗对痴呆高风险糖尿病老年人的认知功能

• 批准号: 9182546
• 负责人: Mary Sano
• 金额: $ 66.38万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9182546
• 关键词: Advertisements; Affect; Aftercare; Age-associated memory impairment; Air; Alzheimer' s Disease; Atmospheric Pressure; Attenuated; Biological; Biological Markers; Blood Glucose; Blood Tests; Blood Vessels; Blood capillaries; Brain; Cellular Phone; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinical Trials; Cognition; Cognitive; Collaborations; Data; Dementia; Diabetes Mellitus; Diagnosis; Elderly; Electronic Mail; Episodic memory; Glucose; Health Services; Hyperbaric Oxygenation; Hyperoxia; Hypoxia; Impaired cognition; Impairment; Individual; Injury; Israel; Lead; Long-Term Effects; Magnetic Resonance Imaging; Measures; Mediating; Mediation; Medical center; Medicine; Memory; Modeling; Multicenter Studies; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Oxygen; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Prevalence; Process; Public Health Applications Research; Publishing; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Registries; Research; Research Infrastructure; Risk; Risk Factors; Source; Spin Labels; Staging; Stroke; Subgroup; Support System; Technology; Testing; Tissues; Treatment Efficacy; Universities; Ursidae Family; Vascular Diseases; Wisconsin; abstracting; balance testing; base; capillary; caregiving; cerebrovascular; cognitive function; cognitive performance; cost; diabetic; effective intervention; effective therapy; executive function; fluorodeoxyglucose positron emission tomography; glucose metabolism; glucose uptake; gray matter; high risk; improved; medical schools; mild cognitive impairment; novel; planetary Atmosphere; pressure; prevent; primary outcome; repaired; secondary outcome; single photon emission computed tomography; social; tissue oxygenation

Abstract This resubmission responds to “PAR-16-365-Pilot Clinical Trials for the Spectrum of Alzheimer’s Disease and Age-related Cognitive Decline (R01)”. It will examine the efficacy of hyperbaric oxygen therapy (HBOT) in improving cognitive functioning in cognitively impaired elderly with diabetes (T2D), who have high risk for dementia. It is a collaboration of the Icahn School of Medicine at Mount Sinai, NY, the University of Wisconsin, the Sagol Center for Hyperbaric Medicine and Research at Asaf Harofeh Medical Center, Israel—one of the world’s largest and busiest hyperbaric units—and the Sheba Medical Center, Israel. HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure above the ambient atmosphere. The combined action of hyperoxia and hyperbaric pressure leads to significant improvements in tissue oxygenation, resulting in cerebrovascular benefits with improved ischemic damage and cerebral blood flow. Recently, our group published compelling evidence from clinical trials indicating HBOT neurotherapeutic effects in stroke, with better cognitive function and elevated brain activity in SPECT. New preliminary data suggests potential neurotherapeutic effects of HBOT on T2D elderly with mild cognitive impairment (MCI), showing better cognitive performance and brain activity. We propose a randomized controlled clinical trial examining the short (12 weeks) and long-term (12 months) efficacy of HBOT. We will test hypotheses that HBOT compared to a sham condition improves cognitive function and increases cerebral blood flow and glucose utilization in MCI patients with T2D. Such patients are at high dementia risk and enriched in cerebrovascular disease, and thus have high potential for benefitting from HBOT. Aim 1 examines the potential beneficial effects of HBOT on cognition (with a primary composite measure of executive functions and episodic memory, both affected by T2D). Aim 2 examines effects of HBOT on ischemic injury which will be measured by CBF at the level of capillaries in gray matter (by MRI arterial spin labeling), and in macrovessels (by a novel 4D Flow MRI technology developed by our group). Aim 3 focuses on effects of HBOT on cerebral glucose utilization using [F18]FDG-PET. Finally, Aim 4 investigates mediation by the biomarkers, i.e. whether their inclusion in a mediation model will attenuate the effect of HBOT on cognition, suggesting them as underlying mechanisms. This study will be performed in Israel, where there is optimal infrastructure and expertise for all the study components at significantly lower costs. HBOT can be widely deployed in the US so if successful, this pilot study will provide the basis for a multi-center large-scale clinical trial for definitive evidence of its benefits to cognition in T2D patients at high dementia risk. Despite advances in our understanding of risk factors and the pathologic basis for dementia, treatments are of very limited effects. As the proportion of elderly increases, the accelerating prevalence of T2D and dementia amplifies this application’s public health impact.

抽象的 这种重新提出对“阿尔茨海默氏病和 与年龄相关的认知下降（R01）”。它将检查高压氧疗法（HBOT）在 糖尿病（T2D）的认知功能改善认知功能，他们的风险很高 失智。这是威斯康星大学纽约州西奈山的伊坎医学院的合作 以色列ASAF HAROFHEH医学中心的Sagol高压医学与研究中心 - 世界上最大，最繁忙的高压单元和以色列的Sheba医疗中心。 HBOT是一种治疗方法，其中富含氧气的空气（高达100％）在压力下给患者施用 在环境气氛上方。高氧和高压压力的综合作用导致显着 组织氧合的改善，从而改善缺血性损伤和 脑血流。最近，我们的小组发表了来自临床试验的令人信服的证据，表明HBOT 中风的神经疗法作用，具有更好的认知功能和SPECT的脑活动升高。新的 初步数据表明，HBOT对T2D的潜在神经治疗作用，较轻度认知 障碍（MCI），显示出更好的认知表现和大脑活动。 我们提出了一项随机对照临床试验，检查短期（12周）和长期（12个月） HBOT的功效。我们将测试与假条件相比HBOT的假设可改善认知 T2D患者的功能并增加了MCI患者的脑血流和葡萄糖利用。这样的患者是 处于高痴呆症风险，富含脑血管疾病，因此具有很高的受益潜力 来自HBOT。 AIM 1考试HBOT对认知的潜在有益影响（具有主要综合材料 执行功能和情节记忆的度量，都受T2D的影响。 AIM 2考试效果HBOT 缺血性损伤将通过CBF在灰质的毛细血管水平上测量（MRI动脉自旋 标签）和宏（通过我们小组开发的新型4D流MRI技术）。 AIM 3重点 使用[F18] FDG-PET的HBOT对脑葡萄糖利用的影响。最后，AIM 4调解调解 通过生物标志物，即它们包含在调解模型中是否会衰减HBOT对 认知，建议它们是基本机制。 这项研究将在以色列进行，所有研究都有最佳的基础架构和专业知识 成本明显降低的组件。 HBOT可以广泛部署在美国，因此，如果成功，该飞行员 研究将为多中心大规模临床试验提供基础 T2D患者处于高痴呆症风险的认知。尽管我们对风险因素和 痴呆的病理基础，治疗的作用非常有限。随着旧的比例增加， 加速T2D和痴呆放大器的患病率这一应用程序的公共卫生影响。