Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training in Alzheimer's Disease (AD_tACSrehab)
Interventional Study to Evaluate the Effectiveness of Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training on Cognitive Performance in Patients With Alzheimer's Disease
The aim of the study is to evaluate the clinical and biological efficacy, as well as predictors of efficacy, of a home-based intervention combining transcranial alternating current stimulation (tACS) with individualized computerized cognitive training in patients with mild Alzheimer's disease (AD).
In neurodegenerative diseases, including AD, neurodegeneration is accompanied by alterations in brain oscillatory activity. Restoration of these oscillations through neuronal entrainment has shown beneficial effects in animal models, while previous studies in patients with AD have demonstrated that gamma-frequency tACS applied over the precuneus is safe and well tolerated and is associated with improvements in cognitive performance and cholinergic function, as well as modulation of brain oscillatory activity. Cognitive rehabilitation may also improve memory performance in patients with mild AD. Based on this evidence, the present study investigates a multimodal approach combining gamma-tACS with individualized computerized memory training.
The study is a multicenter, randomized, placebo-controlled, double-blind trial involving 30 participants with mild AD. Participants will be randomly assigned to one of two groups: Group 1 will receive real gamma-tACS for 8 weeks (5 sessions/week, 60 minutes/session) combined with cognitive training (2 sessions/week, 30 minutes/session); Group 2 will receive sham tACS according to the same schedule, combined with the same cognitive training. tACS will be applied over the precuneus. Treatment will initially be performed in the hospital and will subsequently be administered at home under remote supervision by the study team.
Assessments will be performed at baseline (T00), after 8 weeks of treatment (T08), and at follow-up visits at 16 weeks (T16) and 24 weeks (T24) from baseline. At each time point, participants will undergo clinical and neuropsychological assessment, blood sampling, and transcranial magnetic stimulation (TMS). The occurrence of adverse events will be monitored throughout the duration of the study.
The main objectives of the study are: 1) to evaluate the short- and long-term effects of the combined intervention on cognitive performance; 2) to investigate intervention-induced changes in biological markers of neurodegeneration, inflammation, and synaptic function; 3) to evaluate the effects of the intervention on cholinergic transmission through the TMS short-latency afferent inhibition (SAI) measure; and 4) to investigate potential predictors of treatment efficacy.
研究概览
地位
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习地点
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Milan、意大利
- 尚未招聘
- IRCCS S. Maria Nascente - Fondazione Don Carlo Gnocchi
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接触：
- Francesca Baglio, MD
- 电话号码：+390240308951
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Brescia
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Brescia、Brescia、意大利、25125
- 招聘中
- IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli
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首席研究员：
- Barbara Borroni, MD
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接触：
- Barbara Borroni, MD
- 电话号码：+39 0303501358
- 邮箱：bborroni@fatebenefratelli.eu
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Patients:
- Male or female participants aged ≥18 years at the time of signing the informed consent form;
- Clinical diagnosis of mild Alzheimer's disease (AD) according to current clinical criteria;
- Availability of a caregiver who can assist the participant and who has successfully completed the required training for the use of the device at home.
Caregivers:
- Male or female caregivers aged ≥18 years;
- Compliance with participation in the in-hospital training;
- Mini-Mental State Examination (MMSE) score >27/30.
Exclusion Criteria:
- Age below that specified in the inclusion criteria;
- Inability to understand;
- Contraindications to tACS and TMS (e.g., presence of a cardiac pacemaker or metallic implants incompatible with electrical or magnetic fields, history of epilepsy, or current pregnancy, as assessed using the safety questionnaire).
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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假比较器：假战术
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Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach. 40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of sham tACS applied over the precuneus for a duration of 60 minutes each. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 5 seconds after the start of stimulation, making it impossible for the participant to distinguish between sham and real stimulation. |
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实验性的：Real tACS
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40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of tACS (real, 40 Hz) applied over the precuneus for a duration of 60 minutes each. Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Mini-Mental State Examination (MMSE)
大体时间：Change from baseline to week 24
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The global cognitive functioning will be assessed by Mini-Mental State Examination (MMSE); MMSE scores range from 0 to 30, with higher scores indicating a more preserved cognition. |
Change from baseline to week 24
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Semantic Fluency Test
大体时间：Change from baseline to week 8, 16, and 24
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Lexical-semantic access and executive functioning will be evaluated by Semantic Fluency Test. Participant is asked to generate as many words as possible from a given category within a limited time (60 seconds); higher scores indicate better performance. |
Change from baseline to week 8, 16, and 24
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Trail Making Test (TMT - A, B)
大体时间：Change from baseline to week 8, 16, and 24
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Executive function will be assessed using the Trail Making Test, including Part A (visual attention and processing speed) and Part B (task switching and cognitive flexibility). Higher completion times reflect poorer performance. |
Change from baseline to week 8, 16, and 24
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Rey Auditory Verbal Learning Test (RAVLT)
大体时间：Change from baseline to week 8, 16 and 24
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Verbal memory will be assessed using the Rey Auditory Verbal Learning Test (RAVLT), including immediate recall (sum of trials), delayed recall after 15 minutes. Scores reflect the number of correctly recalled items. |
Change from baseline to week 8, 16 and 24
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Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13)
大体时间：Change from baseline to week 8, 16 and 24
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The ADAS-Cog-13 consists of 13 tasks assessing cognitive domains including memory, language, praxis, orientation, and attention. Total scores range from 0 to 85, with higher scores indicating greater cognitive impairment. |
Change from baseline to week 8, 16 and 24
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Face-Name Associative Memory Test (FNAT)
大体时间：Change from baseline to week 8, 16 and 24
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The Face-Name Associative Memory Test is used to assess the participant's associative memory and is composed of encoding and retrieval phases, with higher scores indicating better function. |
Change from baseline to week 8, 16 and 24
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Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
大体时间：Change from baseline to week 8, 16 and 24
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ADCS-ADL evaluates activities of daily living. The scores range from 0-78 with lower scores indicating more severe functional impairment. |
Change from baseline to week 8, 16 and 24
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Neuropsychiatric Inventory (NPI)
大体时间：Change from baseline to week 8, 16 and 24
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Neuropsychiatric Inventory (NPI) is designed to be a structured clinical interview about neuropsychiatric and behavioral symptoms; the score ranges from 0 (no symptoms) to 144 (severe symptoms). |
Change from baseline to week 8, 16 and 24
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Clinical Dementia Rating scale - Sum of Boxes (CDR-SoB)
大体时间：Change from baseline to week 8, 16 and 24
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The Clinical Dementia Rating-Sum of Boxes (CDR-SB) assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater cognitive and functional impairment. |
Change from baseline to week 8, 16 and 24
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Clinical Dementia Rating scale - Global Score (CDR-GS)
大体时间：Change from baseline to week 8, 16 and 24
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The Clinical Dementia Rating Global Score (CDR-GS) assesses the overall severity of cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment. |
Change from baseline to week 8, 16 and 24
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Zarit Burden Interview (ZBI)
大体时间：Change from baseline to week 8, 16, and 24
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The Zarit Burden Interview (ZBI) assesses the perceived burden experienced by caregivers of individuals with dementia. It consists of 22 items rated on a 5-point scale. Total scores range from 0 to 88, with higher scores indicating greater caregiver burden. |
Change from baseline to week 8, 16, and 24
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in SAI measurements
大体时间：Change from baseline to week 8, 16, and 24
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By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission. SAI is expressed as percent of the unconditioned motor evoked potential. |
Change from baseline to week 8, 16, and 24
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Change From Baseline in Biological Marker Concentrations
大体时间：Change from baseline to week 8, 16, and 24
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A venous blood draw will be performed at each timepoint. Samples will be processed for serum, plasma, and DNA extraction. Changes from baseline in biological marker concentrations, including plasma p-tau217, will be evaluated over time. |
Change from baseline to week 8, 16, and 24
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Demographic characteristics
大体时间：Baseline
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Demographic characteristics (age, gender, and level of education) will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response. |
Baseline
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Baseline Clinical Dementia Rating-Sum of Boxes (CDR-SB)
大体时间：Baseline
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The Clinical Dementia Rating-Sum of Boxes (CDR-SB) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater disease severity. |
Baseline
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Baseline Clinical Dementia Rating - Global Score (CDR-GS)
大体时间：Baseline
|
The Clinical Dementia Rating - Global Score (CDR-GS) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment. |
Baseline
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Level of Education and Occupational Attainment as Proxies of Cognitive Reserve
大体时间：Baseline
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Level of education and occupational attainment will be assessed at baseline as proxy measures of cognitive reserve and examined for associations with differential treatment response. |
Baseline
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Plasma Biomarker Profile
大体时间：Baseline
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The plasma biomarker profile will be evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. |
Baseline
|
合作者和调查者
出版物和有用的链接
一般刊物
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研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.