左前额叶高频重复经颅磁刺激改善阿尔茨海默病精神行为症状的随机双盲对照研究

A randomized,double-blind controlled study on high-frequency repetitive transcranial magnetic stimulation in the left prefrontal lobe to improve psychological and behavioral symptoms in patients with Alzheimer s disease

目的通过随机双盲对照研究,探索左前额叶高频重复经颅磁刺激(repetitivetranscranial magnetic stimulation,rTMS)对阿尔茨海默病(Alzheimer s disease,AD)的精神行为症状(behavioral and psychological symptoms of dementia,BPSD)的疗效及安全性。方法筛选2020年4月至2022年1月在上海市精神卫生中心老年科住院的AD患者45例,年龄6085岁,符合简明精神状况量表(MMSE):224分;临床痴呆评定量表(CDR):13分;Hachinski缺血指数量表(HIS)≤4分;痴呆病理行为评定量表(BEHAVE-AD)≥8分。采用随机、双盲、伪刺激对照的临床实验设计,将患者分为rTMS干预真刺激组和伪刺激组,每天治疗1次,持续约22 min左右,每周5次,4周,共20次,最终完成实验的患者28例(真刺激组13例,伪刺激组15例)。2组均给予常规药物治疗,在基线期和4周干预结束后,分别进行疗效和安全性评估。结果干预后,真刺激组的神经精神症状量表(NPI)、AD病理行为评分表(BEHAVE-AD)及柯恩-曼斯菲尔德激越情绪行为量表(CMAI)的减分高于伪刺激组,分别为(28.85±8.23)vs(8.20±6.79)、(12.85±7.76)vs(7.07±4.57)、(16.31±6.68)vs(9.47±6.86),差异均存在统计学意义(p<0.05);真刺激组的NPI量表妄想、激越、情绪不稳和异常行为4个因子减分高于伪刺激组,差异存在统计学意义(p<0.05);真刺激组抗精神病药物日剂量增量低于伪刺激组(9 vs 50),差异存在统计学意义(p<0.05);真刺激组不良反应为短暂的头皮发紧2例和轻度头痛1例,伪刺激组为短暂的头皮发紧1例和面部肌肉收缩感1例,2组患者均能耐受,发生率无统计学差异,均无严重不良事件。结论左前额叶高频rTMS可能可以改善阿尔茨海默病患者精神行为症状,是一种安全有效的治疗方法。

Objective To explore the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation(rTMS)in the left prefrontal lobe on the psychological and behavioral symptoms(BPSD)of patients with Alzheimer s disease(AD)through a randomized double-blind controlled study.Methods 45 AD patients,aged 60 to 85 years old,who were hospitalized in Department of Geriatric Psychiatry,Mental Health Center of Shanghai City from April 2020 to January 2022,were selected.Their Concise Mental State Scale(MMSE)scores were 2-24,Clinical Dementia Rating Scale(CDR)scores were 1-3,Hachinski Ischemia Index Scale(HIS)scores were≤4,and Dementia Pathological Behavior Rating Scale(Behave-AD)scores were≥8.A randomized,double-blind,pseudo-stimulus-controlled clinical trial design was used to divide the patients into rTMS true stimulation group and pseudo-stimulation group.Patients were treated once a day for about 22 minutes,5 times a week,for a total of 4 weeks and 20 times.Finally,28 patients completed the experiment(13 in the true stimulation group and 15 in the pseudo-stimulation group).Both groups were given conventional drug treatment,and the efficacy and safety were evaluated at baseline and after 4 weeks of intervention.Results After intervention,the reduction scores of Neuropsychiatric Symptom Inventory(NPI),Behavior-AD and Cohn Mansfield Agitated Emotional Behavior Scale(CMAI)in the true stimulation group was higher than that in the pseudo-stimulation group.They were 28.85±8.23 vs 8.20±6.79,12.85±7.76 vs 7.07±4.57,16.31±6.68 vs 9.47±6.86,respectively,with statistical significance(P<0.05).The reduced scores of delusion,agitation,emotional instability,and abnormal behavior in the NPI scale of the true stimulation group were higher than those of the pseudo-stimulation group and the differences were statistically significant(P<0.05).The daily dose increment of antipsychotic drugs in the true stimulation group was significantly lower than that in the pseudo-stimulation group(9 vs 50),and the difference was statistically significant(P<0.05).In the true stimulation group,the adverse reactions were transient scalp tightness in 2 cases and mild headache in 1 case;in the pseudo-stimulation group,the adverse reactions were transient scalp tightness in 1 case and facial muscle contraction in 1 case.Both groups of patients were able to tolerate adverse reactions,and there was no significant difference in incidence.There were no serious adverse events in both groups.Conclusion High frequency rTMS in the left prefrontal lobe may improve the psychological and behavioral symptoms of AD patients,which is a safe and effective treatment method.