The goal of this clinical trial is to learn if repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, can improve short-term memory in people with early Alzheimer's disease (AD). The study will also evaluate the safety of this approach.
The main questions it aims to answer are:
* Does rTMS applied to the cerebellum improve short-term memory in people with early AD? * How does this stimulation affect brain activity and connectivity measured by MRI?
Researchers will compare active rTMS to sham rTMS (a look-alike procedure that does not deliver brain stimulation) to see if rTMS works to improve memory.
Participants will:
* Complete a screening visit with medical and memory assessments * Be randomly assigned to receive either active rTMS or sham rTMS (neither participants nor researchers will know the assignment during treatment) * Receive 20 rTMS sessions over 4 weeks (about 20 to 30 minutes per session) * Undergo two MRI scans, one before and one after treatment * Complete memory and thinking tests and questionnaires at baseline, immediately after treatment, and at 3- and 6-month follow-up visits
Participation in the study will last about 6 months.
The rTMS is generally well tolerated. The most common side effects include mild headache and scalp discomfort during treatment, which are usually short-lasting. MRI is non-invasive and safe for most people. Study procedures will be reviewed to ensure participant safety.
Participants may or may not benefit directly from this study. People who receive active rTMS may experience improvement in memory. This research may help improve understanding of memory function in AD and support development of new treatments.
A clinical diagnosis of early AD, defined as either mild cognitive impairment (MCI) due to AD or mild dementia due to AD;
Evidence of cognitive impairment, characterized by a MMSE score between 20 and 28 and/or a CDR-Sum of Boxes score between 0.5 and 8, consistent with the contemporary definitions used in early AD in clinical trials; and
Biomarker confirmation of AD pathology, demonstrated by a positive plasma phosphorylated tau-217 (p-tau217) result according to the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic guidelines.
Exclusion criteria include evidence of other neurological, psychiatric, or systemic conditions that could cause cognitive and functional impairments (e.g., substantial concomitant cerebrovascular disease, alcoholism, certain medications that could have a substantial effect on cognition, untreated major depressive disorder, and heart, renal or hepatic failure).
Individuals who have contraindications to receiving rTMS, including a history of seizures or any non-removable metal in their heads or within 12 inches of the TMS coil will be excluded.
Parallel
repetitive transcranial magnetic stimulation (rTMS)
DeviceThis is an early phase study investigating the effects of rTMS on individuals with early AD.
sham repetitive transcranial magnetic stimulation rTMS
Other interventionsham rTMS
MMSE
The Mini-Mental State Examination (MMSE) is a widely used 30-point cognitive assessment tool that helps assess domains such as orientation, memory, attention, language and visuospatial skills. It is often used in neurology, geriatrics and clinical research to screen for cognitive impairment and to monitor changes over time. The maximum score is 30 points. The minimum score is 0. A 27-30 score is considered normal range, though subtle cognitive issues may still exist. A 24-26 score may indicate mild cognitive concerns A 20-23 score may be suggestive of mild cognitive impairment or mild dementia A 10-19 score may be suggestive of moderate cognitive impairment A score of less than 10 may be suggestive of severe cognitive impairment
Clinical Dementia Rating scale (CDR)
The Clinical Dementia Rating (CDR) Scale is a clinician-rated staging instrument that assesses the severity of cognitive impairment based on both patient performance and information from an informant (e.g., caregiver or family member). The maximum score is 18. The minimum score is 0. A score of 16-18 indicates severe dementia A score of 9.5-15.5 indicates moderate dementia A score of 4.5-9.0 indicates mild dementia A score of 0.5-4.0 indicates very mild impairment A score of 0 indicates no impairment
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a measure of cognitive impairment. The maximum score if 70. The minimum score is 0. 0-10 Little or no detectable cognitive impairment 10-20 Mild cognitive impairment or very mild dementia 20-35 Mild to moderate Alzheimer's disease 35-50 Moderate to severe cognitive impairment \>50 Severe cognitive impairment
Verbal learning test
The Verbal Learning Test measure episodic verbal memory-the ability to learn, retain, and retrieve spoken information. The maximum score is 75. The minimum score is 0. Higher scores indicate better memory retention. 60-75 Excellent learning 45-59 Average to mildly reduced 30-44 Mild to moderate impairment 15-29 Moderate impairment 0-14 Severe impairment
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Chi-Ying (Roy) Lin
Lead sponsor
Baylor College of Medicine
Sponsor institution
Texas Alzheimer's Research and Care Consortium
Collaborator
