Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Alzheimer's Disease

Not Applicable

Recruiting

• Conditions: Alzheimer Disease
• Interventions: Device: Sham repetitive transcranial magnetic stimulation; Device: Real repetitive transcranial magnetic stimulation

• Registration Number: NCT06385106
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive function in Alzheimer's disease (AD), but studies on the improvement of sleep disorders in AD are limited. The aim of this study was to evaluate the effects of rTMS on sleep and cognition in patients with mild-to-moderate Alzheimer's disease (AD).

Detailed Description

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Some studies have showed that its positive effects in patients with Alzheimer's disease. The aim of this study was to evaluate the effect of rTMS on sleep and cognitive function in patients with mild to moderate AD, and to evaluate the glymphatic system function's mediating role between sleep and cognitive function. The study involves participants receiving 10 sessions of high frequency rTMS treatment applied to the dorsolateral prefrontal cortex over a 5 days period or sham rTMS. Neuropsychological testing and polysomnography will be used as the primary outcome measures. In addition, magnetic resonance imaging will be used to explore the effect of rTMS on the glymphatic system function in patients with Alzheimer's disease. Follow-up assessments of the patients' status will be conducted at one and three-month intervals.

Study Timeline

• Study Start: 2024-03-16
• Study First Submitted: 2024-04-08
• Study First Submitted QC: 2024-04-23
• Study First Posted: 2024-04-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Primary Completion: 2025-12
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Participant meets 2014 IWG-2 criteria for hippocampal amnestic syndrome, typical of AD, with progressive episodic memory impairment confirmed by neuropsychology. Cerebrospinal fluid markers (Aβ40, Aβ42, T-tau, p-tau) consistent with AD, or AV-45 PET imaging showing significant cortical tracer retention, in line with AD pathophysiology.
2. Age range: 55-80 years.
3. No visual or hearing impairment.
4. Right-handed.
5. Han nationality.
6. Signed informed consent.
7. Reliable caregivers as information providers.
8. MMSE score: 10-27; CDR: 0.5-2 points.
9. If receiving approved AD treatment (e.g., acetylcholinesterase inhibitor or memantine), dose must be stable for ≥3 months prior to screening and unchanged unless medically necessary.

Exclusion Criteria

1. History of seizures or epilepsy diagnosis;
2. Stroke history;
3. Nervous system diseases causing brain dysfunction (schizophrenia, severe anxiety/depression, dementia, Huntington's, brain tumors, Parkinson's, metabolic encephalopathy, encephalitis, MS, epilepsy, brain trauma, hydrocephalus);
4. Severe liver/kidney/lung dysfunction, anemia, gastrointestinal disease, arrhythmia, recent MI;
5. Barbiturate/benzodiazepine use within 2 weeks;
6. MRI/TMS contraindications (metallic implants);
7. Systemic diseases causing cognitive impairment (hypothyroidism, folate/B12 deficiency, infections, alcohol/drug abuse);
8. Aphasia, consciousness disturbance, inability to cooperate;
9. TMS/tDCS/DBS has been processed;
10. Underlying pathology other than AD;
11. Focal brain lesions on T1/T2 images;
12. Refusal to sign informed consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham repetitive transcranial magnetic stimulation	Sham repetitive transcranial magnetic stimulation	participants will receive10 sessions of high frequency rTMS treatment applied to the dorsolateral prefrontal cortex over a 5 days sham rTMS
Repetitive transcranial magnetic stimulation	Real repetitive transcranial magnetic stimulation	participants will receive10 sessions of high frequency rTMS treatment applied to the dorsolateral prefrontal cortex over a 5 days real rTMS

Primary Outcome Measures

Name	Time	Method
Cognitive funtion	at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later	Multidimensional neuropsychological assessment is mainly used to assess the cognitive function of patients. Global cognitive assessment included mini-mental state examination (MMSE) and Montreal Cognitive assessment scale (MoCA). MMSE is widely used in cognitive dysfunction which consists of the following ten parts: orientation, memory, attention and numeracy, ability to recall, language skills, including naming ability, retelling ability, three-step command, reading ability, writing ability. The values range from 0 to 30, with higher score indicating better outcome. MoCA is also an assessment tool for rapid screening of cognitive dysfunction, including 8 cognitive domains such as visual structure skills, executive function, memory, language, attention and concentration, calculation, abstract thinking and orientation. The values range from 0 to 30, with higher score indicating better outcome.
Sleep parameters	at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later	Changes in in sleep/wake architecture assessed by polysomnography. Electrodes attached to the scalp near the frontal, central (top) and occipital (back) portions of the brain and provide a readout of different stages of sleep (N1, N2, N3, REM, and Wakefulness). Total sleep time (TST), sleep efficiency (SE), the percentage of rapid eye movement (REM) sleep time in total sleep time, and the percentage of non-rapid eye movement sleep time in total sleep time were mainly analyzed.

Secondary Outcome Measures

Name	Time	Method
glymphatic system	at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later	ALPS-index is a non-invasive diffusion tensor image-based method to measure diffusivity along the perivascular space (ALPS), which measures diffusivity in the direction of the perivascular space in the periventricular white matter. It has been proposed to be an indirect indicator of the state of glymphatic function. ALPS-index = mean(Dxxproj; Dxxasso)/mean(Dyyproj; Dzzasso) Dxxproj means diffusivity along the x-axis in the projection fiber. Dxxassoci means diffusivity along the x-axis in the association fiber. Dyyproj means diffusivity along the y-axis in the projection fiber, Dzzassoci means diffusivity along the z-axis in the association fiber. The values was greater than 0 with lower score indicating more damaged.

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China