Neural and Energetic Drivers of Performance and Perceived Fatigability in Older Adults

老年人表现和感知疲劳的神经和精力驱动因素

• 批准号: 10518828
• 负责人: Caterina Rosano
• 金额: $ 67.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518828
• 关键词: Accounting; Address; Adult; Affect; Age; Aging; Arthritis; Attention; Behavior Therapy; Biopsy; Blood flow; Body mass index; Brain; Cardiopulmonary; Cerebrum; Communities; Complex; Corpus striatum structure; Data; Dementia; Deterioration; Disease; Dopamine; Elderly; Energy Metabolism; Equipment; Exercise Test; Exertion; Fatigue; Feeling; Funding; Gait speed; Heart Rate; Image; Impairment; Individual; Intervention; Knowledge; Lactic acid; Magnetic Resonance Imaging; Measures; Metabolism; Modeling; Motivation; Muscle; Muscle Fatigue; Muscle Mitochondria; Myalgia; Neuraxis; Neurologic; Outcome; Oxygen; Pain; Participant; Patients; Performance; Pharmacology; Physical Performance; Physical activity; Physiological; Population; Positron-Emission Tomography; Prefrontal Cortex; Process; Protocols documentation; Psyche structure; Rehabilitation therapy; Research; Rest; Role; Shortness of Breath; Signal Transduction; Skeletal Muscle; Sleep; Spectrum Analysis; Standardization; System; Testing; Translating; Urine; Variant; Visit; Walking; Weight-Bearing state; Work; age related; base; behavioral pharmacology; brain magnetic resonance imaging; cardiopulmonary system; clinically relevant; comorbidity; cost; cost effective; executive function; fitness; frailty; functional near infrared spectroscopy; improved; innovation; metabolic rate; mortality; multidisciplinary; muscle form; muscle strength; muscular system; neural network; neuroimaging; neurotransmission; novel; relating to nervous system; strength training; symposium; treadmill; young adult

ABSTRACT Higher fatigability, the degree to which someone is physically or mentally limited due to fatigue, is common and disabling in community-dwelling older adults. While fatigue associated with a disease can be ameliorated by targeting the underlying condition, the causes and definitions of fatigability in older age are not well understood and treatments are not available. Studies in older adults show associations with lower muscle mitochondrial function and cardiopulmonary fitness; fitness and strength training can improve fatigability, but benefits are often limited by poor motivation, reduced effort, and impaired locomotor factors (weight bearing pain, arthritis). Fatigability appears influenced by neuro-energetic processes, and specifically striatal dopamine (DA) signaling and cerebral metabolic rate of oxygen. Emerging pharmacologic and behavioral interventions promoting these neuro-energetic processes also appear to reduce fatigability in young healthy adults. However, these findings cannot be translated to older adults because the neuro-energetic contributions to fatigability have not been studied. We propose to address this gap in knowledge and examine the multi-systemic contribution (brain, muscle, cardiopulmonary) to physical performance fatigability (PPF), defined as performance decline during a standardized physical task. Our overarching hypothesis is that higher striatal DA, related networks’ activity, and brain energy metabolism predict lower PPF in older adults; we also propose that these neural markers, individually and in combination explain PPF beyond what is predicted by muscle energetic and cardiopulmonary function. Our recently optimized neuro-energetic imaging protocol uses a state-of-the-art MRI-PET scanner to simultaneously measure striatal DA (PET), cerebral metabolic rate of O2 non-invasively (total brain MRI-based O2 extraction fraction, blood flow), resting state activity of striatal networks; and task-related activation (functional near- infrared spectroscopy of prefrontal cortex during dual tasks). We are currently collecting this protocol at baseline in 150 participants of SOMMA (Study of Muscle, Mobility and Aging),a 3 year longitudinal ongoing study. We propose to relate these neuroimaging measures with objective PPF (slowing down during the fast paced 400m walk), cross- sectionally and longitudinally over 3 years. We leverage the measures that SOMMA is already obtaining: a) perceived fatigability (rating of perceived exertion at end of 5-min treadmill walk; Pittsburgh Fatigability Scale); b) muscle mitochondrial function (biopsy, P31magnetic resonance spectroscopy) and mass; c) cardiopulmonary function (VO2 peak, cardio-pulmonary exercise test); d) locomotor factors (sleep, pain, arthritis, BMI, comorbidities). This innovative research has high potential impact, because it will quantify energetic and metabolic processes in brain, muscle, and cardiopulmonary systems, separately and in combination, in relation to fatigability. This study offers an unprecedented opportunity for a cost-effective, longitudinal, multi-system assessment of determinants of physical performance fatigability.

抽象的 较高的疲劳性，某人因疲劳而在身体或精神上限制的程度很常见，并且 在社区居住的老年人中禁用。虽然与疾病相关的疲劳可以通过 针对潜在条件，年龄较大的疲劳性原因和定义尚不清楚 和治疗不可用。对老年人的研究表明，肌肉线粒体的关联 功能和心肺健康；健身和力量训练可以改善疲劳性，但利益通常是 受动机不良，努力减少和运动因素受损（负重疼痛，关节炎）的限制。 疲劳性似乎受神经能源过程的影响，特别是纹状体多巴胺（DA）信号传导 和氧的大脑代谢率。促进这些的新兴药物和行为干预措施 神经能源过程似乎也可以减少年轻健康成年人的疲劳性。但是，这些发现 不能翻译成老年人，因为尚未研究神经能量的疲劳性贡献。 我们建议在知识方面解决这一差距，并检查多系统的贡献（大脑，肌肉， 心肺对身体性能疲劳（PPF），定义为在 标准化的物理​​任务。我们的总体假设是，较高的纹状体DA，相关网络的活动以及 大脑能量代谢预测老年人的PPF较低。我们还建议这些神经标记，单独 并结合结合解释了PPF超出肌肉能量和心肺功能所预测的。 我们最近优化的神经能量成像协议使用最先进的MRI-PET扫描仪 简单测量纹状体DA（PET），非侵入性O2的脑代谢率（总脑MRI基于O2 提取部分，血流），纹状体网络的静止状态活性；和与任务相关的激活（功能近接近 双重任务期间前额叶皮层的红外光谱）。我们目前正在基线收集此协议 150名Somma的参与者（对肌肉，流动性和衰老研究），一项为期3年的纵向研究。我们建议 为了将这些神经影像措施与客观PPF（快速步行400m步行速度放慢），交叉 分段和纵向超过3年。我们利用Somma已经获得的措施：A） 可感知的疲劳性（在5分钟跑步机步行末的感知劳累的评级；匹兹堡疲劳性量表）； b） 肌肉线粒体功能（活检，p31磁共振光谱）和质量； c）心肺 功能（VO2峰，心肺运动测试）； D）运动因素（睡眠，疼痛，关节炎，BMI，合并症）。 这项创新的研究具有很高的潜在影响，因为它将量化能量和代谢过程 大脑，肌肉和心肺系统，与疲劳性有关。这项研究 为确定的成本效益，纵向多系统评估提供了前所未有的机会 身体绩效疲劳。