Dalrymple W Alex, Huss Diane S, Blair Jamie, Flanigan Joseph L, Patrie James, Sperling Scott A, Shah Binit B, Harrison Madaline B, Druzgal T Jason, Barrett Matthew J
Department of Neurology, University of Virginia, 1221 Lee St 4th Floor, Charlottesville, VA, 22908, USA.
Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA.
J Neurol. 2021 Jan;268(1):95-101. doi: 10.1007/s00415-020-10111-2. Epub 2020 Jul 28.
There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed.
The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients.
We investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex.
Reduced Ch4 GMD was associated with reduced Fast Walking Speed in the "on" medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the "on" medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021).
Reduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD.
有证据表明，皮质胆碱能去神经支配导致帕金森病（PD）患者出现步态和平衡障碍，尤其是步态速度降低。
本研究旨在确定PD患者胆碱能基底前脑灰质密度（GMD）与步态之间的关系。
我们调查了66例接受神经外科手术术前评估以治疗PD运动症状的患者。作为该评估的一部分，患者接受了脑部MRI检查和正式的步态评估。通过将胆碱能基底前脑的概率图谱应用于脑部MRI的基于体素的形态测量，我们计算了胆碱能核4（Ch4）、胆碱能核1、2和3（Ch123）以及整个皮质的灰质密度（GMD）。
Ch4 GMD降低与“开”药状态下的快步行走速度降低相关（FWSON，p = 0.004）。双侧皮质GMD也与FWSON相关（p = 0.009），但Ch123 GMD与FWSON无关（p = 0.1）。在调整Ch4 GMD后，双侧皮质GMD与FWSON无关（p = 0.44）。虽然Ch4 GMD与“开”药状态下的计时起立行走测试（TUG）或认知TUG的改善无关，但Ch4 GMD降低与基于双重任务的更大恶化百分比相关（p = 0.021）。
Ch4 GMD降低与PD患者的步态速度减慢以及PD患者在双重任务期间TUG的更大恶化百分比相关。这些发现对未来研究胆碱能疗法以改善PD患者步态障碍的临床试验规划具有启示意义。
