Department of Neuroscience, University of Catania, Catania, Italy.
J Neural Transm (Vienna). 2011 Apr;118(4):587-98. doi: 10.1007/s00702-010-0554-9. Epub 2011 Jan 5.
Recently, neuropathological studies have shown an important motor cortex involvement in Alzheimer's disease (AD), even in its early stages, despite the lack of clinically evident motor deficit. Transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD patients. This cortical hyperexcitability is believed to be a compensatory mechanism to execute voluntary movements, despite the progressive impairment of associative cortical areas. At present, it is not clear if these motor cortex excitability changes might be the expression of an involvement of intracortical excitatory glutamatergic circuits or an impairment of inhibitory cholinergic and, to a lesser extent, gabaergic activity. Although the main hypothesis for the pathogenesis of AD remains the degeneration of the basal forebrain cholinergic neurons, the development of specific TMS protocols, such as the paired-pulse TMS and the study of the short-latency afferent inhibition, points out the role of other neurotransmitters, such as gamma-amino-butyric acid, glutamate and dopamine. The potential therapeutic effect of repetitive TMS in restoring or compensating damaged cognitive functions, might become a possible rehabilitation tool in AD patients. Based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological brain aging, mild cognitive impairment, AD and other dementing disorders. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodelling of neuronal networks in the pathogenesis of AD.
最近，神经病理学研究表明，即使在阿尔茨海默病（AD）的早期阶段，大脑运动皮层也有重要的参与，尽管临床上没有明显的运动缺陷。经颅磁刺激（TMS）研究表明，AD 患者的皮质兴奋性增强。这种皮质兴奋性增高被认为是执行自主运动的代偿机制，尽管与运动相关的皮质区域逐渐受损。目前尚不清楚这些运动皮层兴奋性变化是否可能是皮质内兴奋性谷氨酸能回路参与的表现，或者是抑制性胆碱能和（在较小程度上）γ-氨基丁酸能活动受损的表现。尽管 AD 发病机制的主要假说仍然是基底前脑胆碱能神经元的退化，但特定 TMS 方案的发展，如成对脉冲 TMS 和短潜伏期传入抑制的研究，指出了其他神经递质（如γ-氨基丁酸、谷氨酸和多巴胺）的作用。重复 TMS 恢复或补偿受损认知功能的潜在治疗效果，可能成为 AD 患者康复的一种手段。基于皮质兴奋性的不同模式，TMS 可能有助于区分生理性脑老化、轻度认知障碍、AD 和其他痴呆症。本综述通过进一步了解不同神经递质通路在 AD 发病机制中的作用以及神经元网络的可塑性重塑，提供了对这些 TMS 技术的展望。
