Effect of Heat Exposure on Cognition in Persons with Higher Cord Lesions

热暴露对高位脊髓损伤患者认知的影响

• 批准号: 9067159
• 负责人: John P Handrakis
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067159
• 关键词: Activities of Daily Living; Address; Adverse effects; Age; Arrhythmia; Attention; Awareness; Behavior; Blood; Blood Pressure; Body Composition; Body Temperature; Cardiac; Centers for Disease Control and Prevention (U.S.); Cervical; Cessation of life; Chronic; Cognition; Cognitive; Comparative Study; Confusion; Data; Depressed mood; Distal; Encephalopathies; Environment; Esthesia; Exposure to; Feeling; Gender; Goals; Headache; Heart Arrest; Heating; Hour; Hyperthermia; Impairment; Individual; Infection; Interruption; Intervention; Judgment; Kidney Failure; Knowledge; Lesion; Limb structure; Liver Failure; Maintenance; Measurement; Measures; Medical; Mental Depression; Methodology; Motor; Nausea; Normal Range; Pain; Paraplegia; Pathway interactions; Peripheral; Persons; Pharmaceutical Preparations; Physiologic Thermoregulation; Physiological; Pilot Projects; Positioning Attribute; Quadriplegia; Quality of life; Recruitment Activity; Reporting; Research; Risk; Sensory; Shivering; Short-Term Memory; Signs and Symptoms; Skin; Skin Temperature; Societies; Spinal cord injury; Sterile coverings; Stupor; Sunlight; Sweat; Sweating; Temperature; Thermogenesis; Thoracic Injuries; Time; Unconscious State; Vasodilation; Ventricular Fibrillation; Veterans; Viscosity; Work; base; carbohydrate metabolism; cognitive function; cognitive performance; diet and exercise; disorder prevention; executive function; improved; insight; instrumentation; insulin sensitivity; lean body mass; memory process; mental function; metabolic rate; natural hypothermia; processing speed; prospective; rectal; response; safety study; sound; spasticity; therapy development; thermal stress; vasoconstriction; warm temperature

After spinal cord injury (SCI), particularly cervical and high thoracic injuries, the motor, sensory, and sympathetic pathways necessary for effective thermoregulation are interrupted, resulting in an impaired ability to maintain core body temperature (Tcore) when exposed to challenges in environmental temperature. Control of distal extremity vasoconstriction (heat conservation) and shivering thermogenesis (heat production) are impaired, and the ability to maintain a constant Tcore is compromised. In addition, changes in body composition (loss of lean body mass) and medications commonly prescribed in persons with SCI may lower metabolic rate and further depress Tcore. Persons with tetraplegia often report “feeling cold,” frequently present with subnormal Tcore (35.5-36.5°C), and are particularly vulnerable to hypothermia (Tcore<35°C), even at temperatures that are comfortable for able-bodied (AB) individuals. The deleterious effects of hypothermia are well appreciated in AB persons with documented progressive decline in various aspects of cognitive performance associated with the magnitude of the depression in Tcore. However, the potential beneficial effects of increasing subnormal Tcore to euthermic levels on cognitive function of those with tetraplegia are not known. In our current submission, we are proposing a prospective two-group comparative study to compare the physiological and cognitive responses to warm exposure in persons with SCI who have subnormal Tcore and in AB persons who are euthermic. Twenty subjects with SCI (C3-T4, AIS A & B; Tcore <37°C) and 20 age/gender-matched AB control subjects will be recruited for study. Subjects will be placed in a thermoneutral (27°C) environment for instrumentation. Measurements of Tcore (rectal thermocouple), skin temperature (skin thermocouple), sweat rate (QSweat methodology), and thermal sensitivity (9-point thermal sensation scale) will be made during 15 minutes of baseline (27°C) and during up to 120 minutes of warm (35°C) temperature exposure while in the seated position. Cognitive performance will be assessed twice, at baseline and after Tcore rises 0.5°C or at the end of the warm challenge. The primary dependent variables will be Tcore and cognitive performance. The secondary dependent variables will be measures of autonomic adaption to a warm environment and include distal skin temperature, sweat rate, and thermal sensitivity. Specific Aims: During exposure to a warm environment (35°C) for up to 120 min in the seated position: Primary Specific Aim: To determine if 2 hours of warm exposure will cause a 0.5°C increase in Tcore and favorably effect cognitive performance (attention, working memory, processing speed, and executive function). Primary Hypotheses: Based on our pilot data: (1) Eighty percent of persons with tetraplegia will demonstrate an increase of 0.5°C in Tcore while none of the AB controls will demonstrate such an increase in Tcore; (2) Eighty percent of persons with tetraplegia will have an increase of at least one T-score in Stroop Interference scores (a validated measure of executive function) while none of the AB controls will demonstrate a change in cognitive performance. Secondary Specific Aims: To determine changes in: (1) The average of distal skin temperatures; (2) Sweat rate; and (3) Subjective rating of thermal sensitivity. Secondary Hypotheses: Persons with tetraplegia will have less of a percent change in average distal skin temperatures and sweat rate, and will report blunted ratings of thermal sensitivity compared to that of AB controls. Our proposed study will confirm our preliminary observations in persons with SCI who have subnormal Tcore to demonstrate in a more definitive manner that cognitive function will be improved by raising Tcore to normal. By rapidly and dramatically reversing the impairment in cognitive function by raising Tcore about 0.5°C to euthermic values, we would anticipate greater functional capacity and independence, enhanced reintegration into society, and improved quality of life, albeit these endpoints are beyond the scope of the current proposal.

脊髓损伤 (SCI)，特别是颈椎和高胸椎损伤后，运动、感觉和 有效体温调节所需的交感神经通路被中断，导致能力受损 当面临环境温度控制挑战时保持核心体温（Tcore）。 远端肢体血管收缩（热量保存）和颤抖产热（热量产生）的 受损，维持恒定 Tcore 的能力也会受到影响。此外，身体也会发生变化。 SCI 患者的成分（去脂体重损失）和常用药物可能会降低 四肢瘫痪的人经常报告“感觉寒冷”。 存在 Tcore 低于正常值 (35.5-36.5°C)，并且特别容易出现体温过低的情况 (Tcore<35°C)， 即使在适合身体健全 (AB) 个体的温度下也会产生有害影响。 体温过低在 AB 人群中很受欢迎，其各个方面都有记录进行性下降。 然而，认知表现与 Tcore 的抑郁程度相关。 将低于正常的 Tcore 增加至常温水平对患有以下疾病的人的认知功能产生有益影响 在我们目前提交的材料中，我们提出了一项前瞻性的两组比较。 研究比较 SCI 患者对温暖暴露的生理和认知反应 Tcore 低于正常以及体温正常的 AB 人 20 名 SCI 受试者（C3-T4，AIS A 和 B；Tcore）。 <37°C）和 20 名年龄/性别匹配的 AB 对照受试者将被招募进行研究。 用于仪器测量的热中性 (27°C) 环境。 温度（皮肤热电偶）、出汗率（QSweat 方法）和热敏度（9 点热敏度） 感觉量表）将在 15 分钟的基线（27°C）和长达 120 分钟的温暖期间进行 将在坐姿时对 (35°C) 温度暴露进行两次评估。 基线和 Tcore 上升 0.5°C 后或温暖挑战结束时，主要因变量将。 次要因变量是自主神经的测量。 对温暖环境的适应，包括远端皮肤温度、出汗率和热敏感性。 具体目标： 在坐姿暴露于温暖环境 (35°C) 长达 120 分钟期间： 主要具体目标：确定 2 小时的温暖暴露是否会导致 Tcore 升高 0.5°C， 对认知表现（注意力、工作记忆、处理速度和执行功能）产生有利影响。 主要假设：根据我们的试点数据：(1) 百分之八十的四肢瘫痪患者会表现出 Tcore 增加 0.5°C，而 AB 对照均不会表现出 Tcore 的这种增加 (2)； 百分之八十的四肢瘫痪患者在斯特鲁普干扰中的 T 分数将增加至少一项 分数（执行功能的有效衡量标准），而所有 AB 对照都不会表现出执行功能的变化 认知表现。 次要具体目标：确定以下方面的变化：(1) 远端皮肤温度的平均值；(2) 出汗量； 率；和（3）热敏感性的主观评级次要假设：四肢瘫痪的人会。 平均远端皮肤温度和出汗率的变化小于百分之一，并且会报告迟钝 与 AB 控制相比的热灵敏度等级。 我们提出的研究将证实我们对 Tcore 低于正常的 SCI 患者的初步观察结果 以更明确的方式证明认知功能将通过将 Tcore 提高到正常而得到改善。 通过将 Tcore 提高约 0.5°C 至 euthermic 价值观，我们预计会有更大的功能能力和独立性，增强重新融入社会 融入社会，提高生活质量，尽管这些终点超出了当前提案的范围。