Department of Rehabilitation, Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Department of Radiology, Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
J Neural Transm (Vienna). 2019 Aug;126(8):1081-1094. doi: 10.1007/s00702-019-02022-y. Epub 2019 Jul 10.
Various studies report discordant results regarding the efficacy, parameters, and underlying mechanisms of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (CT) on Alzheimer's disease (AD). The objective of the study was to assess the effect of rTMS-CT on cognition, the activities of daily life, neuropsychiatric behavioral symptoms, and metabolite levels beneath the stimulated areas of the brain in patients with AD and to investigate the correlation of metabolic changes (measured with proton magnetic resonance spectroscopy [H-MRS]) with clinical outcomes after treatment. Thirty consecutive patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS with CT (i.e., real group) and (2) sham rTMS with CT (i.e., sham group). 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then to stimulate the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks. Each patient underwent neuropsychological assessment at baseline (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). The ratios of N-acetylaspartate/creatine (NAA/Cr), myoinositol/creatine (mI/Cr), and choline/creatine (Cho/Cr) in the stimulated cortex were measured using H-MRS at T0 and T1. Twenty-eight patients were treated with rTMS-CT for 4 weeks. Two patients in the sham group withdrew after being treated several times. Compared with the sham group, the cognitive function and behavior in the real rTMS group improved significantly at T1 and T2. In the real group, compared with the sham group, the NAA/Cr ratio in the left DLPFC was significantly elevated (p = 0.045); however, in the left LTL, it only showed a tendency toward increase (p = 0.162). The change in the NAA/Cr ratio in the left DLPFC was negatively correlated with the change in the cognitive scales of the Alzheimer's Disease Assessment Scale (ADAS-cog). This study indicated a possible modest effect of rTMS-CT on preventing clinical and neuronal functional deterioration in the left DLPFC of patients with AD. The left DLPFC is a better candidate area than the left LTL.
各种研究报告表明，重复经颅磁刺激（rTMS）联合认知训练（CT）对阿尔茨海默病（AD）的疗效、参数和潜在机制存在不一致的结果。本研究的目的是评估 rTMS-CT 对 AD 患者认知、日常生活活动、神经精神行为症状以及刺激脑区下方代谢物水平的影响，并探讨治疗后代谢变化（用质子磁共振波谱 [H-MRS] 测量）与临床结果的相关性。连续纳入 30 例轻度或中度 AD 患者，并随机分为两组干预措施之一：（1）真 rTMS 联合 CT（即真组）和（2）假 rTMS 联合 CT（即假组）。使用 10 Hz rTMS 每天刺激左背外侧前额叶皮质（DLPFC）20 分钟，然后每天刺激左外侧颞叶（LTL）20 分钟，持续 4 周。每位患者在基线（T0）、治疗后即刻（T1）和治疗后 4 周（T2）进行神经心理学评估。在 T0 和 T1 时使用 H-MRS 测量刺激皮质的 N-乙酰天冬氨酸/肌酸（NAA/Cr）、肌醇/肌酸（mI/Cr）和胆碱/肌酸（Cho/Cr）的比值。28 例患者接受 rTMS-CT 治疗 4 周。假组中有 2 例患者在接受几次治疗后退出。与假组相比，真 rTMS 组在 T1 和 T2 时认知功能和行为明显改善。在真组中，与假组相比，左 DLPFC 的 NAA/Cr 比值显著升高（p=0.045）；然而，在左 LTL 中，仅显示出增加的趋势（p=0.162）。左 DLPFC 的 NAA/Cr 比值变化与阿尔茨海默病评估量表（ADAS-cog）认知量表的变化呈负相关。这项研究表明，rTMS-CT 可能对预防 AD 患者左 DLPFC 的临床和神经元功能恶化有一定作用。左 DLPFC 是比左 LTL 更好的候选区域。
