Enhanced episodic memory and LTP-like plasticity in subjective cognitive decline following 10-Hz repetitive transcranial magnetic stimulation

Abstract

Background: Subjective cognitive decline (SCD) is a self-perceived cognitive complaint in the absence of objective impairment, representing an at-risk state along the continuum of cognitive aging. High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) has shown cognitive benefits in Alzheimer’s disease (AD), yet its effects on cognitive functions in SCD remain largely unexplored. Objective: To evaluate the effects of 10-Hz rTMS over the L-DLPFC in individuals with SCD on cognitive functions and long-term potentiation (LTP)-like plasticity, indexed by changes in motor evoked potential (MEP) following intermittent theta burst stimulation, and examine the relationship between brain plasticity and cognitive outcomes. Methods: In this randomized, sham-controlled trial, 42 individuals with SCD received 20 sessions of either active or sham 10-Hz rTMS (n = 21 per group) over four weeks. The primary outcome was delayed episodic memory, evaluated using the Auditory Verbal Learning Test-Huashan version (AVLT-H). Secondary outcomes included additional cognitive measures and MEP amplitudes at baseline and at 5 (T5), 10 (T10), and 30 (T30) minutes post-intervention. Results: The rTMS group exhibited significant improvements in both delayed episodic memory (AVLT-N5) and MEP amplitudes at T5 and T10 following the intervention, whereas such changes were not observed in the sham group. Moreover, increased MEP amplitude at T10 was positively correlated with improved AVLT-N5 performance. Conclusions: These findings provide the first evidence for enhanced delayed episodic memory and LTP-like plasticity in individuals with SCD following 10-Hz rTMS over the L-DLPFC, suggesting a potential role of LTP-like plasticity in elucidating the neurophysiological correlates of cognitive improvements for SCD. Trial registration: The study design and analysis plan were preregistered on September 7th, 2023 at Chinese Clinical Trial Registry (No. ChiCTR2300075517).