Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults

被动热疗可降低中年和老年人的收缩压并改善血管功能

基本信息

批准号：
10712162
负责人：
DOUGLAS R SEALS
金额：
$ 37.56万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10712162
关键词：
Acute Administrative Supplement Adult Aging Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Award Bathing Biological Availability Biomedical Research Blood Blood Pressure Blood Vessels Carbon Dioxide Cerebrovascular Circulation Cerebrovascular Disorders Cerebrovascular system Clinical Clinical Trials Cognitive Country Dementia Disease Elderly Episodic memory Exposure to Finland Frequencies Funding Goals Guidelines Health Hot Springs Human Hypercapnia Hypertension Immersion Impaired cognition Impairment Incidence Intervention Japan Laboratories Life Style Lifestyle Therapy Link Liquid substance Measurement Measures Mediating Nitric Oxide Outcome Oxidative Stress Oxidative Stress Induction Parents Peripheral Physiological Population Study Populations at Risk Production Randomized, Controlled Trials Reactive Oxygen Species Regulation Research Rest Risk Risk Factors Risk Reduction Sauna Serum Short-Term Memory Temperature Therapeutic heat application Translations United States National Institutes of Health Water Work age group aged brain endothelial cell cerebrovascular clinical application cognitive enhancement cognitive function cognitive performance dementia risk efficacy evaluation epidemiology study executive function experimental study follow-up high risk improved in vivo indexing lifestyle intervention middle age middle cerebral artery mild cognitive impairment novel parent grant pharmacologic pilot trial prevent primary outcome processing speed randomized, clinical trials response vascular cognitive impairment and dementia

项目摘要

PROJECT SUMMARY Aging is the primary risk factor for Alzheimer’s disease and related dementias, as well as mild cognitive impairment (MCI). Above-normal systolic blood pressure (SBP; ≥120 mmHg) further increases risk of dementias, due, in part, to SBP-associated cerebrovascular dysfunction, i.e., impaired cerebral blood flow regulation. Accordingly, midlife and older adults with above-normal SBP are at the highest risk for cognitive decline driven by vascular contributions to cognitive impairment and dementias in this age group. Excessive reactive oxygen species-induced oxidative stress and reductions in nitric oxide (NO) bioavailability within the cerebral vasculature likely mediate cerebrovascular dysfunction with aging and contribute to MCI and Alzheimer’s disease and related dementias in those with above-normal SBP. Passive heat therapy (regular short-term increases in body core temperature) is an established lifestyle practice in certain cultures (e.g., sauna bathing in Finland; hot spring bathing in Japan) and may be effective for decreasing risk of dementias. Epidemiological research suggests regular sauna use is associated with ~65% lower incidence of dementias, supporting heat therapy as a powerful candidate approach to significantly reduce risk of dementias. However, randomized controlled trials are urgently needed to establish the causal link between passive heat therapy and risk factors for MCI, Alzheimer’s disease and related dementias. Results from our pilot trial show that 8-10 weeks of heat therapy (hot water immersion 3x1 h/week) lowered SBP (-10 mmHg) and improved cognitive performance and cerebrovascular function vs. sham (thermoneutral water immersion). Heat therapy also reduced vascular markers of oxidative stress and increased NO bioavailability. Our parent award is a randomized clinical trial assessing 3 months (36 x 1 h sessions) of passive heat therapy vs. sham immersion for lowering SBP and improving peripheral vascular function in midlife and older adults with SBP 120-139 mmHg. This proposal will extend the work of our parent grant by assessing the efficacy of heat therapy for: 1) increasing key domains of cognitive performance; 2) improving cerebrovascular blood flow and other measures of cerebrovascular function and health that are closely linked to MCI and dementias; and 3) decreasing oxidative stress and increasing NO-bioavailability, important mechanisms likely underlying cognitive impairment and dementias. This research is highly relevant to MCI and Alzheimer’s disease and related dementias, as it will evaluate a novel lifestyle-based therapy for improving key risk factors for these disorders. Leveraging our existing clinical trial, we will provide the first evidence for the efficacy of passive heat therapy for enhancing cognitive and cerebrovascular function in older adults at risk of developing MCI and Alzheimer’s disease and related dementias. Lastly, the proposed research will also stimulate future research promoting translation of this promising lifestyle intervention to other at-risk groups.

项目摘要衰老是阿尔茨海默氏病和相关痴呆症的主要危险因素，也是轻度认知损害（MCI）。高正常的收缩压（SBP；≥120mmHg）进一步增加了痴呆症，部分原因是SBP相关的脑血管功能障碍，即脑血流受损规定。彼此之间，中年和老年人具有高度SBP的认知风险最高该年龄段的认知障碍和痴呆症的血管贡献驱动的下降。过量的活性氧诱导的氧化应激和一氧化氮（NO）生物利用度的减少在脑脉管系统中，可能会介导脑血管功能障碍，并导致MCI 以及高于正常的SBP患者的阿尔茨海默氏病和相关痴呆症。被动热疗法（定期短期体内核心温度升高）是已建立的生活方式在某些文化中练习（例如，芬兰的桑拿浴浴；日本的温泉沐浴），可能是有效的降低痴呆症的风险。流行病学研究表明，定期使用桑拿与痴呆症的降低〜65％，支持热疗法作为一种强大的候选方法降低痴呆症的风险。但是，迫切需要进行随机对照试验来建立因果关系被动热疗法与MCI，阿尔茨海默氏病和相关痴呆症的危险因素之间的联系。我们的试点试验的结果表明，降低了8-10周的热疗法（热水浸入3x1 h/周） SBP（-10 mmHg）和改善的认知表现和脑血管功能与假手术（热水浸入）。热疗法还降低了氧化应激的血管标志物和没有增加生物利用度。我们的父母奖是一个被动热疗法的3个月（36 x 1 h会话）的随机临床试验评估与降低SBP和改善中年和老年人外周血管功能的假手术浸入与SBP 120-139 mmHg。该提案将通过评估效率来扩大我们父母赠款的工作热疗法的：1）增加认知表现的关键领域； 2）改善脑血管血液与MCI紧密相关的脑血管功能和健康的其他措施痴呆症； 3）减少氧化应激和提高无生物的胁迫，重要机制可能潜在的认知障碍和痴呆症。这项研究与MCI和阿尔茨海默氏症高度相关疾病和相关痴呆症，因为它将评估一种新型基于生活方式的治疗，以改善关键危险因素对于这些疾病。利用我们现有的临床试验，我们将提供第一个证据被动热疗法可增强有发展风险的老年人认知和脑血管功能 MCI和阿尔茨海默氏病和相关痴呆症。最后，拟议的研究还将刺激未来研究将这种有希望的生活方式干预转化为其他高危群体的研究。