Alzheimer’s disease and the therapeutic potential of theta burst stimulation: A systematic review of preclinical and clinical studies
Bibliographic record
Abstract
Abstract Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral impairment. Despite growing research efforts, effective disease-modifying interventions remain elusive. Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), has shown promise in modulating cortical excitability, synaptic plasticity, and neuroprotective mechanisms. This systematic review aimed to evaluate the efficacy and safety of TBS in AD by synthesizing findings from preclinical and clinical studies. Methods A systematic search of PubMed, Scopus, Embase, Web of Science, and the Cochrane Library was conducted up to January 2025. Studies investigating TBS, including intermittent TBS [iTBS] and continuous TBS [cTBS], in human patients with AD or in animal models of AD were included. Primary outcomes included cognitive function and neuropsychiatric symptoms. Secondary outcomes included biomarkers of neuroplasticity and neurodegeneration. The risk of bias was assessed using the Joanna Briggs Institute (JBI) and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tools. Results Twenty studies met the inclusion criteria, comprising six preclinical and 14 clinical studies. Preclinical evidence suggests that TBS reduces amyloid-beta deposition, enhances synaptic plasticity, mitigates neuroinflammation and oxidative stress, and improves cognitive performance in animal models of AD. iTBS targeting the dorsolateral prefrontal cortex (DLPFC) improved cognitive function, depression, anxiety, and activities of daily living, with some studies reporting non-significant findings in specific neuropsychological assessments. Neuroplasticity changes were observed in motor-evoked potentials and resting motor thresholds, with lower responses in patients with AD and variable reproducibility over time. Additionally, structural and functional brain changes, including preserved hippocampal volume and enhanced frontal beta activity, were associated with cognitive improvements. Adverse events were mild and well-tolerated. Conclusion Preclinical studies robustly support the neuroprotective and neuropsychiatric effects of TBS in AD models. Clinical findings suggest possible benefits of TBS, particularly iTBS over the DLPFC; however, clinical results are inconsistent and limited by small sample sizes and protocol variability. These findings highlight the challenges of translating animal data to humans and underscore the need for larger, controlled randomized clinical trials to confirm safety and efficacy and optimize treatment parameters.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.031 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.009 |
| Bibliometrics | 0.010 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".