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Randomized Controlled Trial
. 2025 Sep 26;22(1):195.
doi: 10.1186/s12984-025-01738-1.

Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial

Cheng-Chang Yang #  1   2 , Ko-Yen Huang #  3 , Jung-Lung Hsu  4   5 , Chaur-Jong Hu  1   6   7   8 , Yueh-Hsun Lu  7   9   10 , Yi-Chun Kuan  11   12   13   14   15
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Randomized Controlled Trial

Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial

"V体育安卓版" Cheng-Chang Yang et al. J Neuroeng Rehabil. .

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in alleviating cognitive symptoms in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Although animal studies suggest rTMS may enhance glymphatic system efficiency and reduce amyloid deposits, its impact on human glymphatic activity remains uncertain. VSports手机版.

Methods: This double-blind, randomized, sham-controlled trial investigated the effects of intermittent theta-burst stimulation (iTBS), a novel rTMS technique, on cognitive function and glymphatic system activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) in 52 participants with amnestic MCI or very mild AD. Participants underwent 10 sessions of iTBS targeting the left dorsolateral prefrontal cortex over two weeks. Cognitive and glymphatic assessments were conducted at baseline, week 2, and week 6 V体育安卓版. Of the 52 participants, 28 received active iTBS, while 24 received sham stimulation. After the first two weeks, the sham group transitioned to active iTBS. .

Results: Significant cognitive improvements were observed at week 6 in the iTBS group, indicating delayed cognitive enhancement, though no immediate changes in cognition or glymphatic system activity (measured by the ALPS index) were observed. No adverse events were reported V体育ios版. .

Conclusions: These findings suggest that iTBS can produce delayed cognitive enhancement in individuals with amnestic MCI and very mild AD, while the impact on the glymphatic system remains uncertain and requires further investigation. VSports最新版本.

Trial registration: Clinicaltrials. gov (NCT04555941). V体育平台登录.

Keywords: Alzheimer’s disease; Diffusion tensor image analysis along the perivascular space (DTI-ALPS); Glymphatic system; Intermittent theta burst stimulation; Mild cognitive impairment; Transcranial magnetic stimulation VSports注册入口. .

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Conflict of interest statement

Declarations V体育官网入口. Ethics approval and consent to participate: Ethical approval for our trial was obtained from the Taipei Medical University-Shuang Ho Hospital (TMU-JIRB No. N202003022). The study was conducted in accordance with the Declaration of Helsinki and its subsequent revisions. Consent was obtained from all participants before enrollment in the trial. Consent for publication: Consent for publication was obtained from participants prior to enrollment in the study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of participant enrollment, group allocation, and the timeline for pre-iTBS and post-iTBS evaluations
Fig. 2
Fig. 2
Comparison of baseline MMSE scores (A) and ALPS indices (B) between the experimental and control groups
Fig. 3
Fig. 3
Comparison of MMSE score changes (A) and ALPS index changes (B) at week 2 between the experimental and control groups
Fig. 4
Fig. 4
MMSE scores (A) and ALPS indices (B) before and after 2 weeks of active iTBS in the experimental group
Fig. 5
Fig. 5
(A) Significant increase in MMSE scores at week 6 compared to baseline in the experimental group. (B) No significant difference in ALPS indices between week 6 and baseline in the experimental group
See this image and copyright information in PMC

"V体育ios版" References

    1. Knopman DS, Amieva H, Petersen RC, Chetelat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33. - PMC - PubMed
    1. Griffith HR, Netson KL, Harrell LE, Zamrini EY, Brockington JC, Marson DC. Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction over a two-year time period. J Int Neuropsychol Soc. 2006;12(2):166–75. - PubMed
    1. Michaud TL, Su D, Siahpush M, Murman DL. The risk of incident mild cognitive impairment and progression to dementia considering mild cognitive impairment subtypes. Dement Geriatr Cogn Disord Extra. 2017;7(1):15–29. - PMC - PubMed
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    1. World Health Organization. Dementia 2023 [updated 15 March 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia

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