Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy; Stroke Unit, Tor Vergata Policlinic, Viale Oxford 81, 00133, Rome, Italy.
Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy.
Neuroimage. 2018 Apr 1;169:302-311. doi: 10.1016/j.neuroimage.2017.12.048. Epub 2017 Dec 19.
Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN. Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.
记忆丧失是典型阿尔茨海默病（AD）的首发症状之一，但目前尚无有效的治疗方法。最近人们强调，顶内小（PC）是 AD 早期观察到的记忆障碍的关键区域，这可能是由于默认模式网络（DMN）等大规模网络内的断开机制所致。我们采用多模态方法，在一项为期两周、随机、假对照、双盲试验中，研究了高频重复经颅磁刺激（rTMS）对 14 名早期 AD 患者（7 名女性）认知的影响，认知由阿尔茨海默病合作研究临床前阿尔茨海默认知综合指标测量。TMS 结合脑电图（TMS-EEG）用于检测脑连接变化。我们发现，PC 的 rTMS 可选择性改善情景记忆，但对其他认知领域没有影响。TMS-EEG 信号分析显示，患者 PC 中的神经活动增加，β波段的脑振荡增强，PC 与 DMN 内内侧额区之间的功能连接发生改变。我们的研究结果表明，PC 的高频 rTMS 是一种有前途的、非侵入性治疗早期 AD 患者记忆功能障碍的方法。这种临床改善伴随着脑连接的调节，与 AD 中脑连接中断的病理生理模型一致。
