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）后，尤其是颈部和高位胸部损伤后，运动、感觉和 有效的体温调节所必需的交感神经通路被中断，导致能力受损 当暴露于环境温度的挑战时，维持核心体温（Tcore）。控制 远端肢体血管收缩（热保存）和寒战产热（产热）的发生是 受损，并且维持恒定Tcore的能力受到损害。此外，身体的变化 成分（瘦体重减轻）和SCI患者常用的药物可能会降低 代谢率，并进一步降低Tcore。四肢瘫痪的人经常报告“感到寒冷”， 存在低于正常的Tcore（35.5-36.5°C），并且特别容易出现体温过低（Tcore<35°C）， 即使在对于健全（AB）个体而言舒适的温度下。的有害影响 体温过低在AB型患者中得到了很好的评价， 与Tcore中抑郁程度相关的认知表现。然而，潜在的 将低于正常的Tcore增加到正常体温水平对认知功能的有益影响 四肢瘫痪是未知的。在我们目前提交的文件中，我们提出了一个前瞻性的两组比较， 研究比较了SCI患者对温暖暴露的生理和认知反应， 低Tcore和体温正常的AB型人。20例SCI患者（C3-T4，AIS A&B; Tcore <37°C）和20名年龄/性别匹配的AB对照受试者将被招募用于研究。受试者将被安排在 热中性（27°C）环境。测量Tcore（直肠热电偶）、皮肤 温度（皮肤热电偶）、出汗率（QSweat方法）和热敏感性（9点热 将在基线（27°C）的15分钟期间和在长达120分钟的温热（27°C）期间进行测量。 (35°C）温度暴露，而在坐的位置。认知表现将评估两次， 在基线和Tcore升高0.5°C后或在热激发结束时。主要因变量将 是Tcore和认知性能。次要因变量将是自主神经功能的测量。 适应温暖的环境，并包括远端皮肤温度，出汗率和热敏感性。 具体目的：在坐姿下暴露于温暖环境（35°C）长达120 min期间： 主要特定目的：确定2小时的热暴露是否会导致Tcore升高0.5°C， 有利地影响认知表现（注意力、工作记忆、处理速度和执行功能）。 主要假设：根据我们的试点数据：（1）80%的四肢瘫痪患者将表现出 Tcore增加0.5°C，而AB对照组均未显示Tcore增加;（2） 80%的四肢瘫痪患者在Stroop干扰中至少增加一个T评分 分数（执行功能的有效测量），而AB对照组中没有一个将证明 认知绩效 次要特定目的：确定以下各项的变化：（1）远端皮肤温度的平均值;（2）出汗 （3）热敏感性的主观评定。次要假设：四肢瘫痪的人 平均远端皮肤温度和出汗率的变化小于百分之一， 与AB对照相比的热敏感性等级。 我们建议的研究将证实我们在Tcore低于正常的SCI患者中的初步观察结果 以更明确的方式证明认知功能将通过将Tcore升高至正常而得到改善。 通过将Tcore升高约0.5°C至1.5 °C， 我们会期望更大的功能能力和独立性， 社会的发展和生活质量的提高，尽管这些终点超出了目前提案的范围。