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

Official title

Effects of Repetitive Transcranial Magnetic Stimulation on Sleep and Cognitive Function in Patients With Alzheimer's Disease: a Randomized, Double-blind, Controlled Study

Overview

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.

Interventions

• Device Real repetitive transcranial magnetic stimulation
  The target brain region for stimulation was the left dorsolateral prefrontal lobe. The intensity of the stimulation was 80% of the resting motor threshold (MT) of each subject. In the target brain region, we applied 40 stimuli at a frequency of 20 Hz and the MT for 1600 pulses per session.
• Device Sham repetitive transcranial magnetic stimulation
  The target brain region for stimulation was the left dorsolateral prefrontal lobe. The intensity of the stimulation was 80% of the resting motor threshold (MT) of each subject. In the target brain region, we applied 40 stimuli at a frequency of 20 Hz and the MT for 1600 pulses per session. The patients were applied with the coil angled away from the head to reproduce the noise of the stimulation as well as some local sensation

Primary outcome measures

• Cognitive funtion [Time frame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later]
• Sleep parameters [Time frame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later]

Secondary outcome measures (1)

• glymphatic system [Time frame: at baseline (T0), immediately after the end of the treatment (T1), 1month later (T2),3months later]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Zhejiang University — Hangzhou

Publications

• You S, Lv T, Qin R, Hu Z, Ke Z, Yao W, Zhao H, Bai F. Neuro-Navigated rTMS Improves Sleep and Cognitive Impairment via Regulating Sleep-Related Networks' Spontaneous Activity in AD Spectrum Patients. Clin Interv Aging. 2023 Aug 15;18:1333-1349. doi: 10.2147/CIA.S416992. eCollection 2023. PMID 37601952
• Siow TY, Toh CH, Hsu JL, Liu GH, Lee SH, Chen NH, Fu CJ, Castillo M, Fang JT. Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults. Neurology. 2022 Feb 22;98(8):e829-e838. doi: 10.1212/WNL.0000000000013215. Epub 2021 Dec 14. PMID 34906982
• Herring WJ, Ceesay P, Snyder E, Bliwise D, Budd K, Hutzelmann J, Stevens J, Lines C, Michelson D. Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimers Dement. 2020 Mar;16(3):541-551. doi: 10.1002/alz.12035. Epub 2020 Jan 15. PMID 31944580

Identifiers

NCT: NCT06385106 · rTMS in AD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗