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 较高的疲劳度是指某人因疲劳而在身体或精神上受到限制的程度，这是很常见的， 社区老年人的残疾可以通过以下方式缓解： 针对潜在的状况，老年疲劳的原因和定义尚不清楚 且尚无针对老年人的研究表明其与较低的肌肉线粒体有关。 功能和心肺健康；健身和力量训练可以改善疲劳，但好处往往是 受到动力不足、努力减少和运动因素受损（负重疼痛、关节炎）的限制。 疲劳似乎受到神经能量过程的影响，特别是纹状体多巴胺 (DA) 信号传导 和脑氧代谢率促进这些。 神经能量过程似乎也可以降低年轻健康成年人的疲劳程度。但是，这些发现。 不能应用于老年人，因为尚未研究神经能量对疲劳的影响。 我们建议解决这一知识差距，并研究多系统的贡献（大脑、肌肉、 心肺）到身体表现疲劳性（PPF），定义为在一段时间内表现下降 我们的首要假设是更高的纹状体 DA、相关网络的活动和 大脑能量代谢预测老年人的 PPF 较低；我们还提出，这些神经标记物分别 并结合起来解释 PPF 超出肌肉能量和心肺功能的预测。 我们最近优化的神经能量成像协议使用最先进的 MRI-PET 扫描仪来 同时无创测量纹状体 DA (PET)、脑 O2 代谢率（基于全脑 MRI 的 O2 提取分数、血流量）、纹状体网络的静息状态活动和任务相关激活（功能性近端激活）； 双重任务期间前额皮质的红外光谱）我们目前正在收集该协议的基线。 SOMMA（肌肉、活动性和衰老研究）的 150 名参与者是一项为期 3 年的纵向持续研究。 将这些神经影像学测量与客观 PPF（在快节奏的 400m 步行过程中放慢速度）联系起来， 我们在 3 年内分段和纵向地利用 SOMMA 已经获得的措施：a) 感知疲劳性（5 分钟跑步机步行结束时的感知疲劳程度；匹兹堡疲劳量表 b）； 肌肉线粒体功能（活检、P31 磁共振波谱）和质量 c) 心肺； 功能（VO2 峰值、心肺运动测试）；d) 运动因素（睡眠、疼痛、关节炎、BMI、合并症）。 这项创新研究具有很高的潜在影响，因为它将量化体内的能量和代谢过程。 这项研究分别和结合了大脑、肌肉和心肺系统与疲劳性的关系。 为对影响因素的决定因素进行具有成本效益的、纵向的、多系统的评估提供了前所未有的机会 身体机能 疲劳程度。