Cappon Davide, Fox Rachel, den Boer Tim, Yu Wanting, LaGanke Nicole, Cattaneo Gabriele, Perellón-Alfonso Ruben, Bartrés-Faz David, Manor Brad, Pascual-Leone Alvaro
Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, Boston, MA, United States.
Deanna and Sidney Wolk Center for Memory Health at Hebrew SeniorLife, Boston, MA, United States.
Front Hum Neurosci. 2023 Jun 2;17:1168673. doi: 10.3389/fnhum.2023.1168673. eCollection 2023.
Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS).
Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD.
All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus -0.64 ± 3.28 and Taper -2.56 ± 5.03 Phases.
This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350.
https://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350.
目前全球有超过5500万人被诊断患有阿尔茨海默病（AD），并伴有使人衰弱的情景记忆缺陷。目前的药物治疗效果有限。最近，经颅交流电刺激（tACS）通过使高频神经元活动正常化，已显示出对AD患者记忆的改善作用。在此，我们研究一种创新方案的可行性、安全性及其对情景记忆的初步影响，该方案是在研究伙伴的帮助下，在患有AD的老年人家中进行tACS治疗（HB-tACS）。
八名被诊断患有AD的参与者连续接受多次针对左侧角回（AG）的高清HB-tACS治疗（40赫兹，20分钟），AG是记忆网络的关键节点。急性期包括14周的HB-tACS治疗，每周至少进行五次。三名参与者在14周急性期前后接受静息态脑电图（EEG）检查。随后，参与者进入为期2至3个月的间歇期，在此期间不接受HB-tACS治疗。最后，在减量期，参与者在3个月内每周接受2至3次治疗。主要结局指标为安全性（通过副作用和不良事件报告确定）和可行性（通过对研究方案的依从性和遵守情况确定）。主要临床结局指标为记忆和整体认知，分别通过记忆指数评分（MIS）和蒙特利尔认知评估（MoCA）进行测量。次要结局指标为EEG的θ/γ比值。结果以平均值±标准差报告。
所有参与者均完成了研究，每位参与者平均完成97次HB-tACS治疗；25%的治疗过程报告有轻微副作用，5%为中度，1%为重度。急性期的依从率为98±6.8%，减量期为125±22.3%（超过100%的比率表明参与者完成的治疗次数超过每周最少2次的要求）。急性期后，所有参与者的记忆均有改善，MIS为7.25±3.77，与基线相比，在间歇期（7.00±4.90）和减量期（4.63±2.39）持续保持。对于接受EEG检查的三名参与者，观察到AG区的θ/γ比值降低。相反，参与者在MoCA测试中没有改善，急性期后为1.13±3.80，在间歇期（-0.64±3.28）和减量期（-2.56±5.03）有适度下降。
这项初步研究表明，针对患有AD的老年人的基于家庭、远程监督、由研究伙伴实施的多通道tACS方案是可行且安全的。此外，针对左侧AG区，该样本的记忆得到了改善。这些是初步结果，需要进行更大规模、更明确的试验，以进一步阐明HB-tACS干预的耐受性和疗效。NCT04783350。
https://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1，标识符NCT04783350
