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Targeting Default Mode Network Dysfunction in Persons at Risk of Alzheimer’s Disease with Transcranial Magnetic Stimulation (NEST4AD): Rationale and Study Design
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-08-27 , DOI: 10.3233/jad-210659
Michela Pievani 1 , Anna Mega 1 , Giulia Quattrini 1, 2 , Giacomo Guidali 3 , Clarissa Ferrari 4 , Annamaria Cattaneo 5, 6 , Ilari D'Aprile 5 , Lorella Mascaro 7 , Roberto Gasparotti 8 , Daniele Corbo 8 , Debora Brignani 3, 9 , Marta Bortoletto 3
Affiliation  

Background:Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. Objective:This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. Methods:We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. Results:We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. Conclusion: The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

中文翻译:

使用经颅磁刺激 (NEST4AD) 针对阿尔茨海默病风险人群的默认模式网络功能障碍:基本原理和研究设计

背景:默认模式网络 (DMN) 功能障碍在阿尔茨海默病 (AD) 中得到了很好的证实,并且在临床前阶段和有风险的受试者中都有记录,因此代表了潜在的疾病目标。多次重复经颅磁刺激 (rTMS) 似乎能够调节健康个体和 AD 患者的 DMN 动态和记忆;然而,这种方法在高危受试者中的潜力还有待测试。目的:本研究将测试 rTMS 对携带 AD 最强遗传风险因素——载脂蛋白 E (APOE) ɛ4 等位基因的健康老年人的 DMN 的影响。方法:我们将招募64名没有认知缺陷的老年参与者,32名APOEɛ4等位基因携带者和32名非携带者作为参考组。参与者将接受四次 rTMS 活动(高频)或假 DMN 刺激。多模态成像检查(包括结构、静息和任务功能 MRI 和扩散张量成像)、TMS 与同步脑电图 (TMS-EEG) 和认知评估将在基线和刺激会话后进行。结果:我们将通过静息态功能性 MRI 和 TMS-EEG 评估 DMN 连接的变化,以及 APOE ɛ4 携带者的记忆性能变化。我们还将通过评估与神经元活动、兴奋性和多模态成像结构连通性的测量的相关性来研究 DMN 调制的机制。结论:这项研究的结果将告知有 AD 风险的受试者的 DMN 刺激的生理和认知结果以及可能的机制。这些结果可能会勾勒出未来 AD 非药物预防干预的设计。
更新日期:2021-08-29
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