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左侧顶叶重复经颅磁刺激改善阿尔茨海默病患者的认知功能,并调节静息态脑连接:BDNF 和氧化应激的可能作用。

Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer's disease: Possible role of BDNF and oxidative stress.

机构信息

Istanbul Medipol University, Health Sciences and Technology Research Institute (SABITA), Regenerative and Restorative Medicine Research Center (REMER), functional Imaging and Cognitive-Affective Neuroscience Lab (fINCAN), Istanbul, Turkey.

Istanbul Medipol University, Health Sciences and Technology Research Institute (SABITA), Regenerative and Restorative Medicine Research Center (REMER), functional Imaging and Cognitive-Affective Neuroscience Lab (fINCAN), Istanbul, Turkey; Istanbul Medipol University School of Medicine, Department of Neurology, Istanbul, Turkey.

出版信息

Neurobiol Learn Mem. 2021 Apr;180:107410. doi: 10.1016/j.nlm.2021.107410. Epub 2021 Feb 18.

Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer's Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

摘要

重复经颅磁刺激(rTMS)是一种非侵入性的神经调节技术,越来越多地用于治疗阿尔茨海默病(AD)患者的认知障碍。尽管 rTMS 已被证明可以改变脑源性神经营养因子(BDNF)和许多神经和精神疾病中的氧化应激水平,但仍没有研究评估 rTMS 后 AD 患者的记忆表现、BDNF、氧化应激和静息大脑连接之间的关系。此外,越来越多的临床数据表明,刺激战略大脑区域可能会导致记忆功能的改善比常规 rTMS 更显著。在这项研究中,我们旨在评估 rTMS 对与海马体连接最高的 AD 患者外侧顶叶皮层的可能疾病修饰作用。为了填补上述研究空白,我们评估了静息态功能磁共振成像(fMRI)、认知评分、外周血 BDNF 水平和总氧化/抗氧化状态之间的关系,以解释 rTMS 的治疗和潜在疾病修饰作用,rTMS 已应用于 20Hz 频率两周。我们的研究结果表明,视觉识别记忆功能和时钟绘制测试评分显著提高,与外周 BDNF 水平升高和氧化应激状态降低有关,在左侧顶叶 TMS 刺激两周后。临床上,我们的研究结果表明,针对左侧顶叶区域的 rTMS 应用导致与左侧顶叶区域和海马体之间的网络连接相关的熟悉认知显著改善。

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