Background Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. Methods In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Results Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Discussion Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.

中文翻译：

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社区老年人较高的纹状体多巴胺与较低的身体表现易疲劳性相关


背景 社区老年人中的疲劳现象非常普遍并导致残疾，但缺乏治疗方法。更强的黑质纹状体多巴胺能信号传导可以改善健康年轻人的表现疲劳性，但其在社区老年人中的作用尚不清楚。我们假设较高的黑质纹状体多巴胺能完整性与较低的运动疲劳性相关，与心肺和肌肉骨骼能量学以及其他健康状况无关。方法 在参与肌肉、活动性和衰老研究的 125 名老年人中，通过快速 400 米步行期间的表现恶化（从第 2 圈到第 9 圈减速的百分比）来测量表现疲劳度。使用 (+)-[11C]二氢丁苯那嗪 (DTBZ) PET 成像测量黑质纹状体 DA 完整性。分别获得调节感觉运动（后壳核）、奖赏（腹侧纹状体）和执行控制过程（背侧纹状体）的亚区域的结合信号。表现疲劳性（因变量）的多变量线性回归模型估计了纹状体分区中多巴胺完整性的系数，并根据人口统计、合并症和认知进行了调整。模型进一步针对骨骼肌能量学（通过活检）和心肺健康（通过心肺运动测试）进行调整。结果 后壳核中较高的 [11C]-DTBZ 结合与较低的疲劳性能显着相关（人口统计学调整的标准化 Beta = -1.08，95% CI：-1.96，-0.20）；结果仍然独立于其他协变量的调整，包括心肺和肌肉骨骼能量学。与其他纹状体亚区域的关联并不显着。 讨论 感觉运动纹状体中的多巴胺能完整性可能会影响没有临床明显疾病的老年人的表现疲劳性，独立于其他衰老系统。