帕金森病胆碱能神经末梢易损性与平衡自我效能的关系。
Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.
机构信息
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Functional Neuroimaging, Cognitive, and Mobility Laboratory, University of Michigan, Ann Arbor, MI 48106, USA.
出版信息
J Integr Neurosci. 2024 Sep 24;23(9):178. doi: 10.31083/j.jin2309178.
BACKGROUND
Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refers to one's level of confidence in their ability to balance while completing activities of daily living like getting dressed, bathing, and walking. Lower self-efficacy, or greater FoF during these activities is a function of motor, cognitive, and emotional impairments and may impact quality of life in PD. Unlike known cholinergic reduction, especially in the right lateral geniculate and caudate nuclei, little is known about the role of cholinergic transporters in FoF or mobility self-efficacy in PD.
METHODS
[F]fluoroethoxybenzovesamicol ([F]FEOBV) positron emission tomography (PET) studies were conducted to assess vesicular acetylcholine transporter (VAChT) expression in 126 patients with PD (male (m) = 95, female (f) = 31). Participants had a mean age of 67.3 years (standard deviation (SD) = 7.1) and median Hoehn Yahr stage of 2.5. Patients also completed the Short Falls Efficacy Scale (sFES-I) as a survey measure of concerns about falling. [F]FEOBV data were processed in Statistical Parametric Mapping (SPM) using a voxel-wise regression model with sFES-I scores as the outcome measure.
RESULTS
Reduced [F]FEOBV binding in tectum, metathalamic (lateral more than medial geniculate nuclei), thalamus proper, bilateral mesiotemporal (hippocampal, parahippocampal, fusiform gyri and fimbriae), and right cerebellar lobule VI significantly associated with higher sFES-I scores ( < 0.05, family-wise error (FWE) correction after Threshold-Free Cluster Enhancement (TFCE)).
CONCLUSIONS
Unlike the more limited involvement of the brainstem-thalamic complex and caudate nuclei cholinergic topography associated with falls in PD, cholinergic reductions in the extended connectivity between the thalamic complex and the temporal limbic system via the fimbriae associates with FoF. Additional cholinergic changes were seen in the cerebellum. The temporal limbic system plays a role not only in episodic memory but also in spatial navigation, scene and contextual (, emotional) processing. Findings may augur novel therapeutic approaches to treat poor mobility self-efficacy in PD.
CLINICAL TRIAL REGISTRATION
No: NCT02458430. Registered 18 March, 2015, https://www.
CLINICALTRIALS
gov/study/NCT02458430; No: NCT05459753. Registered 01 July, 2022, https://www.
CLINICALTRIALS
gov/study/NCT05459753.
背景
姿势不稳和步态障碍（PIGD）是帕金森病（PD）致残的重要原因。胆碱能系统功能障碍与 PD 中的跌倒有关。跌倒通常会导致跌倒恐惧（FoF），进而导致平衡自我效能感下降。平衡自我效能感是指一个人在完成穿衣、洗澡和行走等日常生活活动时对自己平衡能力的信心程度。在这些活动中，较低的自我效能感或更大的 FoF 是运动、认知和情绪障碍的功能，可能会影响 PD 患者的生活质量。与已知的胆碱能减少（特别是在右侧外侧膝状体和尾状核）不同，关于 FoF 或 PD 中移动性自我效能感的胆碱能转运体的作用知之甚少。
方法
使用[F]氟乙基苯甲氧基苯甲酰胺([F]FEOBV)正电子发射断层扫描(PET)研究评估 126 名 PD 患者（男性(m)=95，女性(f)=31）的囊泡型乙酰胆碱转运体(VAChT)表达。参与者的平均年龄为 67.3 岁（标准差(SD)=7.1），中位 Hoehn Yahr 分期为 2.5。患者还完成了简短跌倒效能量表(sFES-I)作为对跌倒担忧的调查测量。[F]FEOBV 数据使用基于体素的回归模型在统计参数映射(SPM)中进行处理，以 sFES-I 评分作为结果测量。
结果
与 PD 中与跌倒相关的中脑-丘脑复合体和尾状核胆碱能分布的更有限的参与不同，丘脑复合体和通过穹窿与颞叶边缘系统之间的扩展连接中的胆碱能减少与 FoF 显著相关（<0.05，在阈值自由聚类增强（TFCE）后进行的全脑错误率（FWE）校正）。
结论
与 PD 中与跌倒相关的中脑-丘脑复合体和尾状核胆碱能分布的更有限的参与不同，丘脑复合体和通过穹窿与颞叶边缘系统之间的扩展连接中的胆碱能减少与 FoF 相关。在小脑中还观察到了其他的胆碱能变化。颞叶边缘系统不仅在情景记忆中起作用，而且在空间导航、场景和上下文（情绪）处理中也起作用。这些发现可能预示着治疗 PD 中移动性自我效能感差的新的治疗方法。
临床试验注册
否：NCT02458430。注册于 2015 年 3 月 18 日，https://www.。
临床试验
NCT02458430；否：NCT05459753。注册于 2022 年 7 月 1 日，https://www.。
临床试验
NCT05459753。
Zotero 插件