Paalanen N, Roytman S, Emde Boas M van, Biddix A, Luker A, Michalakis F, Carli G, Kanel P, Pongmala C, Koeppe R, Chahine L M, Rosano C, Bohnen N I
Department of Neurology, University of Michigan, Ann Arbor, MI 48105-9755, USA.
Department of Radiology, University of Michigan, Ann Arbor, MI 48105-9755, USA.
Clin Park Relat Disord. 2025 May 31;12:100353. doi: 10.1016/j.prdoa.2025.100353. eCollection 2025.
Slow walking in healthy older adults may result from multifactorial deficits involving the muscular, peripheral, and central nervous systems. While mobility depends on these systems, the brain's neuromodulatory capacity may offer insights for interventions. This open-label imaging study tested whether the dopaminergic system serves as a resilience mechanism for gait in the elderly. Using [C]PE2I dopamine transporter (DAT) PET, we assessed whether baseline dopaminergic innervation modulates the response to a one-week carbidopa-levodopa regimen in slow-walking older adults without Parkinson's disease (PD).
Slow walking older adults without clinical evidence of PD (n = 9) were pre-treated with carbidopa 25 mg one tablet TID for three days, followed by carbidopa-levodopa 25/100 mg starting at one tablet TID for three days and then increased to 1.5 tablets of carbidopa-levodopa 25/100 mg TID daily for four days, as tolerated. [C]PE2I DAT PET imaging was completed at baseline. Spatiotemporal gait parameters were evaluated at pre-intervention, following carbidopa pre-treatment, and post-intervention.
Levodopa treatment resulted in improved gait speed ( = 0.69 [0.07, 1.30], = 0.031), double-support time ( = -0.26 [-0.51, -0.01], = 0.041), and cadence ( = 0.54 [0.18, 0.89], = 0.005), but not in turn duration ( = 0.41 [-0.33, 1.14], = 0.264). These changes were strongly predicted by pre-treatment limbic, subcortical, and neocortical DAT PET uptake, with greater improvements in gait pace observed among individuals with lower DAT availability.
These preliminary findings suggest that the mesocorticolimbic dopaminergic system may be the substrate of a resilience mechanism that can be targeted to manage gait impairments in older adults.
健康老年人行走缓慢可能是由涉及肌肉、外周和中枢神经系统的多因素缺陷导致的。虽然行动能力取决于这些系统，但大脑的神经调节能力可能为干预措施提供思路。这项开放标签成像研究测试了多巴胺能系统是否作为老年人步态的恢复机制。使用[C]PE2I多巴胺转运体（DAT）PET，我们评估了基线多巴胺能神经支配是否调节无帕金森病（PD）的行走缓慢老年人对为期一周的卡比多巴-左旋多巴治疗方案的反应。
无PD临床证据的行走缓慢老年人（n = 9）先服用卡比多巴25毫克，每日三次，每次一片，共三天，然后服用卡比多巴-左旋多巴25/100毫克，开始时每日三次，每次一片，共三天，然后根据耐受情况增加至每日三次，每次1.5片卡比多巴-左旋多巴25/100毫克，共四天。在基线时完成[C]PE2I DAT PET成像。在干预前、卡比多巴预处理后和干预后评估时空步态参数。
左旋多巴治疗导致步态速度改善（= 0.69 [0.07, 1.30]，= 0.031）、双支撑时间改善（= -0.26 [-0.51, -0.01]，= 0.041）和步频改善（= 0.54 [0.18, 0.89]，= 0.005），但周转时间无改善（= 0.41 [-0.33, 1.14]，= 0.264）。这些变化可通过治疗前边缘系统、皮层下和新皮层DAT PET摄取强烈预测，在DAT可用性较低的个体中观察到步态速度有更大改善。
这些初步发现表明，中脑皮质边缘多巴胺能系统可能是一种恢复机制的基础，可针对该机制来管理老年人的步态障碍。
