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

• 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
• 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' s disease related dementia; Alzheimer' 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

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 衰老是阿尔茨海默病和相关痴呆症的主要危险因素， 损害（MCI）。收缩压正常（SBP; ≥120 mmHg）进一步增加了以下风险： 痴呆症，部分原因是与SBP相关的脑血管功能障碍，即，脑血流受损 调控因此，SBP高于正常值的中年和老年人的认知功能障碍风险最高。 在这个年龄组中，血管对认知障碍和痴呆的贡献导致了这种下降。 过量活性氧诱导的氧化应激和一氧化氮（NO）生物利用度的降低 脑血管系统内可能介导脑血管功能障碍与衰老，并有助于MCI 和老年痴呆症及相关痴呆症。 被动热疗（定期短期增加身体核心温度）是一种既定的生活方式 在某些文化中的实践（例如，芬兰的桑拿浴;日本的温泉浴），并可能有效 来降低痴呆症的风险流行病学研究表明，经常使用桑拿浴与 痴呆症的发病率降低约65%，支持热疗法作为显着改善痴呆症的有力候选方法 降低痴呆症的风险。然而，迫切需要随机对照试验来确定因果关系。 被动热疗与MCI、阿尔茨海默病和相关痴呆症的风险因素之间的联系。 我们的初步试验结果表明，8-10周的热疗（热水浸泡3x 1小时/周）降低了 与假手术组相比，SBP（-10 mmHg）以及认知能力和脑血管功能改善 （热中性水浸泡）。热疗还减少了氧化应激的血管标志物， 增加NO的生物利用度。 我们的父母奖是一项随机临床试验，评估3个月（36 x 1小时）的被动热疗 vs.模拟浸泡降低中老年人收缩压和改善外周血管功能 收缩压120-139 mmHg。这项建议将通过评估以下方面的功效， 热疗：1）增加认知表现的关键领域; 2）改善脑血管血液 脑血管功能和健康的其他指标与MCI密切相关， 痴呆症;和3）降低氧化应激和增加NO-生物利用度，可能是重要的机制 潜在的认知障碍和痴呆。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的基于生活方式的治疗方法，以改善关键的风险因素 治疗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，证明 被动热疗增强老年人的认知和脑血管功能 MCI和阿尔茨海默病及相关痴呆症。最后，拟议的研究也将刺激未来 促进将这种有前途的生活方式干预措施转化为其他高危群体的研究。