Effects of accelerated DLPFC-rTMS on cognition, EEG activity, and blood biomarkers in Alzheimer’s disease

Repetitive transcranial magnetic stimulation (rTMS) may offer a noninvasive intervention for Alzheimer’s disease (AD), but optimal protocols and mechanisms remain uncertain. We assessed clinical outcomes, resting-state electroencephalography (EEG), and blood biomarkers after a brief accelerated-rTMS application targeting bilateral dorsolateral prefrontal cortex (DLPFC). Thirty-three patients with mild–moderate AD were randomized to accelerated rTMS ( n = 19) or non-stimulated control ( n = 14). The rTMS group received 20-Hz stimulation to each DLPFC twice daily for five days (10 sessions). At baseline and four weeks later, participants completed cognitive testing, neuropsychiatric evaluation, resting EEG, and blood assays of oxidative stress, inflammatory, and neurotrophic markers. Compared with controls, rTMS produced greater improvement in activities of daily living and neuropsychiatric symptoms, with global cognition remaining stable over post‑treatment assessment. Exploratory EEG analyses indicated increased parietal beta-band power following rTMS, although between-group EEG effects did not remain significant after correction for multiple comparisons. Blood measures shifted toward a more neuroprotective profile, including higher neurotrophic signaling and more favorable oxidative and inflammatory indices. No serious adverse events were reported. A one-week accelerated rTMS protocol was feasible and well tolerated in AD, showing aligned improvements in function, EEG, and blood biomarkers, supporting accelerated-rTMS as a feasible and biologically promising intervention that warrants confirmation in sham-controlled trials.