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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Mini-Mental State Examination (MMSE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Real tACS
干预措施: Transcranial Alternating Current Stimulation (Device)
Real tACS
干预措施: Individualized Computerized Memory Training (Behavioral)
Sham tACS
干预措施: Sham Transcranial Alternating Current Stimulation (Device)
Sham tACS
干预措施: Individualized Computerized Memory Training (Behavioral)
结局指标
主要结局
Mini-Mental State Examination (MMSE)
时间窗: Change from baseline to week 24
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.
Semantic Fluency Test
时间窗: Change from baseline to week 8, 16, and 24
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.
Trail Making Test (TMT - A, B)
时间窗: Change from baseline to week 8, 16, and 24
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.
Rey Auditory Verbal Learning Test (RAVLT)
时间窗: Change from baseline to week 8, 16 and 24
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.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13)
时间窗: Change from baseline to week 8, 16 and 24
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.
Face-Name Associative Memory Test (FNAT)
时间窗: Change from baseline to week 8, 16 and 24
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.
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
时间窗: Change from baseline to week 8, 16 and 24
ADCS-ADL evaluates activities of daily living. The scores range from 0-78 with lower scores indicating more severe functional impairment.
Neuropsychiatric Inventory (NPI)
时间窗: Change from baseline to week 8, 16 and 24
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).
Clinical Dementia Rating scale - Sum of Boxes (CDR-SoB)
时间窗: Change from baseline to week 8, 16 and 24
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.
Clinical Dementia Rating scale - Global Score (CDR-GS)
时间窗: Change from baseline to week 8, 16 and 24
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.
Zarit Burden Interview (ZBI)
时间窗: Change from baseline to week 8, 16, and 24
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.
次要结局
- Change in SAI measurements(Change from baseline to week 8, 16, and 24)
- Change From Baseline in Biological Marker Concentrations(Change from baseline to week 8, 16, and 24)
- Demographic characteristics(Baseline)
- Baseline Clinical Dementia Rating-Sum of Boxes (CDR-SB)(Baseline)
- Baseline Clinical Dementia Rating - Global Score (CDR-GS)(Baseline)
- Level of Education and Occupational Attainment as Proxies of Cognitive Reserve(Baseline)
- Plasma Biomarker Profile(Baseline)
研究者
Prof. Barbara Borroni
Professor
IRCCS Centro San Giovanni di Dio Fatebenefratelli