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.

摘要