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<p>Repetitive transcranial magnetic stimulation (rTMS) improves cognition in Alzheimer’s disease (AD), yet its biomarker and neuroplasticity effects remain unclear. Cognitive scale scores, plasma biomarker levels, and resting-state fMRI brain network in AD patients were analyzed before and after a 14-day 20&#xa0;Hz rTMS intervention. The results demonstrated that rTMS intervention significantly improved cognitive performance (MMSE: <i>Z</i> =  − 2.863, <i>q</i> = 0.017; MoCA: <i>t</i> =  − 6.137, <i>q</i> &lt; 0.001; RAVLT_I: <i>t</i> =  − 3.436, <i>q</i> = 0.011) and reduced neuropsychiatric symptoms (NPI: <i>Z</i> =  − 2.547, <i>q</i> = 0.037; HAMD: <i>Z</i> =  − 3.472, <i>q</i> = 0.009). A 9.4% reduction in neurofilament light chain levels was demonstrated (<i>Z</i> =  − 2.371, <i>P</i> = 0.018), with baseline p-Tau181 levels being inversely correlated to Aβ42 changes (<i>R</i> =  − 0.428, <i>P</i> = 0.033). Enhanced global efficiency (GE:<i> t</i> =  − 1.865, <i>P</i> = 0.081, <i>r</i> = 0.423) and increased connection density (CD: <i>Z</i> =  − 1.823, <i>P</i> = 0.068, <i>r</i> = 0.442) were identified in neural networks. Notably, GE improvements positively correlated with elevated Aβ42/40 (<i>R</i> = 0.596, <i>P</i> = 0.025), while cognitive gains measured by the MoCA were significantly associated with network reorganization metrics (GE: <i>R</i> = 0.486, <i>P</i> = 0.048; CD: <i>R</i> = 0.514, <i>P</i> = 0.035). rTMS demonstrates potential in mitigating neurodegeneration by enhancing brain network integration and modulating Aβ metabolism. This effect was particularly pronounced in early-stage AD patients who exhibit preserved neural integrity. These findings advance therapeutic assessment frameworks and decode TMS neuromodulation mechanisms. The trial was prospectively registered (ChiCTR2400080657, ClinicalTrials.gov; 2024–02-04).</p> Graphical Abstract <p></p>

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rTMS modulates early AD progression via synergistic brain network reorganization and peripheral biomarker dynamics

  • 期刊论文

  • 发表日期：

    2025年9月27日

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  • Tian Wang,
  • Miaomiao Guo,
  • Hao Wu,
  • Shuai Liu,
  • Yong Ji,
  • Pan Wang,
  • Guizhi Xu

摘要

Repetitive transcranial magnetic stimulation (rTMS) improves cognition in Alzheimer’s disease (AD), yet its biomarker and neuroplasticity effects remain unclear. Cognitive scale scores, plasma biomarker levels, and resting-state fMRI brain network in AD patients were analyzed before and after a 14-day 20 Hz rTMS intervention. The results demonstrated that rTMS intervention significantly improved cognitive performance (MMSE: Z =  − 2.863, q = 0.017; MoCA: t =  − 6.137, q < 0.001; RAVLT_I: t =  − 3.436, q = 0.011) and reduced neuropsychiatric symptoms (NPI: Z =  − 2.547, q = 0.037; HAMD: Z =  − 3.472, q = 0.009). A 9.4% reduction in neurofilament light chain levels was demonstrated (Z =  − 2.371, P = 0.018), with baseline p-Tau181 levels being inversely correlated to Aβ42 changes (R =  − 0.428, P = 0.033). Enhanced global efficiency (GE: t =  − 1.865, P = 0.081, r = 0.423) and increased connection density (CD: Z =  − 1.823, P = 0.068, r = 0.442) were identified in neural networks. Notably, GE improvements positively correlated with elevated Aβ42/40 (R = 0.596, P = 0.025), while cognitive gains measured by the MoCA were significantly associated with network reorganization metrics (GE: R = 0.486, P = 0.048; CD: R = 0.514, P = 0.035). rTMS demonstrates potential in mitigating neurodegeneration by enhancing brain network integration and modulating Aβ metabolism. This effect was particularly pronounced in early-stage AD patients who exhibit preserved neural integrity. These findings advance therapeutic assessment frameworks and decode TMS neuromodulation mechanisms. The trial was prospectively registered (ChiCTR2400080657, ClinicalTrials.gov; 2024–02-04).

Graphical Abstract