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阿尔茨海默病患者γ tACS 暴露:一项随机、双盲、假刺激对照、交叉、初步研究。

Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study.

机构信息

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

出版信息

Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.

Abstract

OBJECTIVE

To assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer's disease (MCI-AD).

METHODS

In this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to γ-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-γ-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-γ-tACS or sham tACS were evaluated.

RESULTS

Twenty MCI-AD participants completed the study. No tACS-related side effects were observed, and the intervention was well tolerated in all participants. We observed a significant improvement at the Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 to 7.4], p < 0.001) and long delayed recall scores (1.3 [95% CI, 0.4 to 2.1], p = 0.007) after γ-tACS but not after sham tACS. Face-name associations scores improved during γ-tACS (4.3 [95% CI, 2.8 to 5.8], p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission evaluated with TMS, increased only after γ-tACS (0.31 [95% CI, 0.24 to 0.38], p < 0.001) but not after sham tACS.

CONCLUSIONS

exposure to γ-tACS over Pz showed a significant improvement of memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, compared to sham tACS.

摘要

目的

评估经颅交流电刺激(transcranial alternating current stimulation,tACS)γ 频段(γ-tACS)刺激 Pz(覆盖内侧顶叶皮层和楔前叶的区域)是否可改善阿尔茨海默病相关轻度认知障碍(Alzheimer's disease,MCI-AD)患者的记忆,并调节胆碱能传递。

方法

在这项随机、双盲、假刺激对照、交叉先导研究中,参与者被分配至单次 60 分钟 Pz 区γ-tACS 或假 tACS 暴露治疗。所有受试者均接受临床评估,包括γ-tACS 或假刺激前后的情景记忆评估。γ-tACS 或假 tACS 前后采用经颅磁刺激(transcranial magnetic stimulation,TMS)评估间接的胆碱能传递测量。

结果

20 名 MCI-AD 参与者完成了这项研究。未观察到 tACS 相关的不良反应,所有参与者均能很好地耐受干预。我们观察到,与假 tACS 相比,γ-tACS 后 Rey 听觉言语学习测试(Rey auditory verbal learning test,RAVL)总回忆(5.7[95%置信区间,4.0 至 7.4],p<0.001)和长延迟回忆评分(1.3[95%置信区间,0.4 至 2.1],p=0.007)显著改善。γ-tACS 后面孔-名字关联测试(face-name associations test)评分改善(4.3[95%置信区间,2.8 至 5.8],p<0.001),但假 tACS 后无改善。用 TMS 评估的胆碱能传递的短潜伏期传入抑制,一种间接的测量指标,仅在γ-tACS 后增加(0.31[95%置信区间,0.24 至 0.38],p<0.001),但假 tACS 后无增加。

结论

与假 tACS 相比,γ-tACS 刺激 Pz 可显著改善记忆表现,并恢复胆碱能神经传递的皮质内连接测量。

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