Uehara Maria Anabel, Kalia Sumeet, Campuzano Mari Garcia, Jafari-Jozani Mohammad, Lithgow Brian, Moussavi Zahra
Biomedical Engineering, University of Manitoba, Winnipeg, MB R3T 5V6, Canada.
Department of Statistics, University of Manitoba, Winnipeg, MB R3T 5V6, Canada.
Medicina (Kaunas). 2025 Apr 19;61(4):757. doi: 10.3390/medicina61040757.
: Transcranial alternating current stimulation (tACS) at 40 Hz has shown potential to enhance cognitive function. However, research on its combination with cognitive exercises, particularly its long-term effects in a dementia population, remains limited. This study investigated the effects of 40 Hz tACS paired with simultaneous cognitive exercises on cognition, neuropsychiatric symptoms, and the depression status of individuals with dementia in a sham-controlled, double-blind crossover design. : A total of 42 participants with dementia were randomized into two groups: (1) the R1S2 group received 40 Hz real tACS with cognitive exercises, followed by a ≥8-week washout period, and then sham tACS with cognitive exercises; (2) the S1R2 group received the reversed sequence. tACS was applied at 1.5 mA peak-to-peak with electrodes over the left dorsolateral prefrontal cortex and contralateral supraorbital area. Participants received two 30 min stimulation sessions per day, 5 days per week, for 4 consecutive weeks, paired with cognitive exercises using the MindTriggers app (2.9.1). The primary outcome was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the secondary outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). All outcome measures were assessed before and after each treatment block. : Real tACS paired with cognitive exercises significantly improved ADAS-Cog scores post-treatment compared to pre-treatment (-value = 0.019), whereas sham tACS did not. Furthermore, real tACS produced significant long-term improvements approximately 2-3 months post-treatment in ADAS-Cog scores compared to sham (-value = 0.048). Both real (-value = 0.003) and sham (-value = 0.015) tACS significantly reduced NPI-Q scores post-treatment. MADRS scores significantly improved (-value = 0.007) post-treatment for real tACS but not sham. : The 40 Hz tACS paired with cognitive exercises improves cognition, neuropsychiatric symptoms, and depression post-treatment in dementia, with sustained cognitive effects. The findings highlight its potential as a non-invasive therapeutic intervention for dementia.
40赫兹的经颅交流电刺激（tACS）已显示出增强认知功能的潜力。然而，关于其与认知训练相结合的研究，尤其是对痴呆症患者的长期影响，仍然有限。本研究采用假对照、双盲交叉设计，调查了40赫兹tACS与同步认知训练相结合对痴呆症患者认知、神经精神症状和抑郁状态的影响。
共有42名痴呆症患者被随机分为两组：（1）R1S2组先接受40赫兹的真实tACS并进行认知训练，随后有≥8周的洗脱期，然后接受假tACS并进行认知训练；（2）S1R2组接受相反的顺序。tACS以峰峰值1.5毫安施加，电极置于左侧背外侧前额叶皮层和对侧眶上区域。参与者每天接受两次30分钟的刺激，每周5天，连续4周，同时使用MindTriggers应用程序（2.9.1）进行认知训练。主要结局指标是阿尔茨海默病评估量表 - 认知子量表（ADAS - Cog），次要结局指标包括蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）和神经精神科问卷（NPI - Q）。所有结局指标在每个治疗阶段前后进行评估。
与治疗前相比，真实tACS与认知训练相结合在治疗后显著改善了ADAS - Cog评分（P值 = 0.019），而假tACS则没有。此外，与假tACS相比，真实tACS在治疗后约2 - 3个月时使ADAS - Cog评分产生了显著的长期改善（P值 = 0.048）。真实tACS（P值 = 0.003）和假tACS（P值 = 0.015）在治疗后均显著降低了NPI - Q评分。真实tACS治疗后MADRS评分显著改善（P值 = 0.007），而假tACS则没有。
40赫兹tACS与认知训练相结合可改善痴呆症患者治疗后的认知、神经精神症状和抑郁状况，并具有持续的认知效果。这些发现突出了其作为痴呆症非侵入性治疗干预手段的潜力。
