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

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.

Inclusion criteria

• 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.
• Age range: 55-80 years.
• No visual or hearing impairment.
• Right-handed.
• Han nationality.
• Signed informed consent.
• Reliable caregivers as information providers.
• MMSE score: 10-27; CDR: 0.5-2 points.
• 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

• History of seizures or epilepsy diagnosis;
• Stroke history;
• 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);
• Severe liver/kidney/lung dysfunction, anemia, gastrointestinal disease, arrhythmia, recent MI;
• Barbiturate/benzodiazepine use within 2 weeks;
• MRI/TMS contraindications (metallic implants);
• Systemic diseases causing cognitive impairment (hypothyroidism, folate/B12 deficiency, infections, alcohol/drug abuse);
• Aphasia, consciousness disturbance, inability to cooperate;
• TMS/tDCS/DBS has been processed;
• Underlying pathology other than AD;
• Focal brain lesions on T1/T2 images;
• Refusal to sign informed consent.