Adjunctive treatment with high frequency repetitive transcranial magnetic stimulation for the behavioral and psychological symptoms of patients with Alzheimer's disease: a randomized, double-blind, sham-controlled study

Shanghai Arch Psychiatry. 2015 Oct;27(5):280-8. doi: 10.11919/j.issn.1002-0829.215107.


Background: Behavioral and psychological symptoms of dementia (BPSD) occur in 70-90% of patients at different stages of Alzheimer's Disease (AD), but the available methods for managing these problems are of limited effectiveness.

Aim: Assess the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS), applied over the left dorsolateral prefrontal cortex (DLPFC), on BPSD and cognitive function in persons with AD.

Methods: Fifty-four patients with AD and accompanying BPSD were randomly divided into an intervention group (n=27) and a control group (n=27). In addition to standard antipsychotic treatment, the intervention group was treated with 20Hz rTMS five days a week for four weeks, while the control group was treated with sham rTMS.The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), and the Treatment Emergent Symptom Scale (TESS) were administered by raters who were blind to the group assignment of patients before and after four weeks of treatment.

Results: Twenty-six subjects from each group completed the study. After four weeks of antipsychotic treatment with adjunctive real or sham rTMS treatment, the mean (sd) total BEHAVE-AD scores and mean total ADAS-Cog scores of both groups significantly decreased from baseline. After adjusting for baseline values, the intervention group had significantly lower scores (i.e., greater improvement) than the control group on the BEHAVE-AD total score, on five of the seven BEHAVE-AD factor scores (activity disturbances, diurnal rhythm, aggressiveness, affective disturbances, anxieties and phobias), on the ADAS-Cog total score, and on all four ADAS-Cog factor scores (memory, language, constructional praxis, and attention). The proportion of individuals whose behavioral symptoms met a predetermined level of improvement (i.e., a drop in BEHAVE-AD total score of > 30% from baseline) in the intervention group was greater than that in the control group (73.1% vs.42.3%, X (2)=5.04, p=0.025).

Conclusion: Compared to treatment of AD with low-dose antipsychotic medications alone, the combination of low-dose antipsychotic medication with adjunctive treatment with high frequency rTMS can significantly improve both cognitive functioning and the behavioral and psychological symptoms that often accompany AD.

背景: :70-90%的阿尔茨海默氏病(Alzheimer's Disease, AD)患者在不同阶段都伴有痴呆的精神与行为症状(behavioral and psychological symptoms of dementia, BPSD), 但现有的针对这些问题的方法疗效十分有限。.

目的: 评估对AD患者的左背外侧前额叶皮层(left dorsolateral prefrontal cortex, DLPFC)进行高频重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)对其BPSD和认知功能的疗效。.

方法: 将54例伴有BPSD的AD患者随机分为干预组(n=27)和对照组(n=27)。在常规抗精神病药物治疗的基础上, 干预组采用20 Hz的rTMS治疗, 每周五天, 共四周;而对照组采用伪磁刺激治疗。评估者采用阿尔茨海默病行为病理学评定量表(Behavioral Pathology in Alzheimer's Disease Rating Scale, BEHAVE-AD)、阿尔茨海默氏病评估量表-认知分量表(Alzheimer's Disease Assessment Scale-Cognitive, ADAS-Cog)和副反应量表(Treatment Emergent Symptom Scale, TESS)对患者分别在4周治疗期前后进行盲法评估。.

结果: 每组都有26例患者完成了研究。抗精神病药治疗辅以磁刺激或伪磁刺激治疗4周后, 两组BEHAVEAD总分的均值(标准差)和ADAS-Cog总分的均值与基线相比均显著降低。校正基线值后, 干预组的BEHAVE-AD总分、BEHAVE-AD的7个因子分中5个(活动障碍、昼夜节律、攻击性、情感障碍、焦虑和恐惧)、ADAS总分以及ADAS量表4个因子分(记忆、语言、结构性练习、注意力)均显著低于对照组(即改善更明显)。事先将BEHAVE-AD总分比基线下降大于等于30%定义为症状改善, 干预组中行为症状改善的患者比例显著高于对照组(73.1% vs.42.3%, X2=5.04, p=0.025)。.

结论: 相较于单纯低剂量抗精神病药物治疗, 高频rTMS辅助低剂量抗精神病药物治疗能显著改善AD患者的认知功能和精神行为症状。.

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Keywords: Alzheimer’s disease; China; behavioral and psychological symptoms; cognitive function; transcranial magnetic stimulation.

Grants and funding

This study was supported by the Wuxi Science and Technology Development Project (CSE31N1323).