Department of Rheumatology and Geriatrics, The First Hospital of Fuyang Hangzhou, No. 429, Beihuan Road, Hangzhou, 311400, Zhejiang, China.
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 86 Wujin Road, Shanghai, 200080, China.
Adv Ther. 2022 Jan;39(1):286-295. doi: 10.1007/s12325-021-01964-8. Epub 2021 Oct 29.
Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown.
A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55 years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4 weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5 h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5 h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment.
After 2 weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4 weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2 week's treatment and 17.33 ± 3.11 at 4 week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups.
These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.
阿尔茨海默病(AD)通常伴有不同程度的行为和心理症状(BPSD)。经颅磁刺激(TMS)已被应用于 AD 的治疗,作为一种无痛且非侵入性的治疗方法。然而,不同频率的重复经颅磁刺激(rTMS)在 AD 伴 BPSD 中的疗效尚不清楚。
共纳入 32 例有精神行为症状的 AD 患者作为研究对象。其中,高频 TMS 组 16 例,平均病程 6.22±2.55 年;低频 TMS 组性别、年龄匹配,平均病程 7.02±3.33 年。高频 TMS 组以 80% MT 刺激强度,10Hz 频率,每次 0.5h,每天 2 次进行 TMS 治疗,4 周为一疗程;低频 TMS 组以 2Hz 频率,每次 0.5h,每天 1 次进行 TMS 治疗,4 周为一疗程。采用行为病理评定量表(BEHAVE-AD)评分评估神经心理状态;采用日常生活能力量表(ADL)评估行为能力;采用简易精神状态检查量表(MMSE)评估认知功能。采用双抗体夹心酶联免疫吸附法检测血浆中β淀粉样蛋白 40 和 42(Aβ40 和 Aβ42)的水平。所有患者在实验前后均行脑部磁共振成像(MRI)检查。
治疗 2 周后,高频 TMS 组患者的 BEHAVE-AD 和 ADL 评分均显著低于治疗前,且在治疗 4 周后继续下降;低频 TMS 组的 BEHAVE-AD 和 ADL 评分也显著低于治疗前。组间不同时间点比较显示,高频 TMS 组患者的 BEHAVE-AD 和 ADL 评分均显著低于低频 TMS 组。高频 TMS 治疗患者的 MMSE 评分从治疗前的 14.22±3.55 分增加到第 2 周的 14.67±2.22 分和第 4 周的 17.33±3.11 分(p<0.01),而低频 TMS 组分别为 14.19±3.47、14.28±3.41 和 14.49±2.79。第 4 周时,高频 TMS 组治疗前后血浆 Aβ40 无变化。高频与低频 TMS 组之间的血浆 Aβ42 无影响。两组治疗期间不良反应发生率相当。
这些结果表明,高频 TMS 治疗 AD 患者精神行为异常起效快、疗效好、安全性高。此外,本研究提示高频 TMS 干预可进一步改善 AD 患者的认知功能。