Gamma‐band transcranial alternating current stimulation in amnestic mild cognitive impairment: A pilot study

Abstract

AbstractBackgroundAmnestic mild cognitive impairment (aMCI) is a pre‐dementia stage of Alzheimer’s disease (AD) associated with dysfunctional episodic memory and limited treatment options. Recent findings from animal models of AD show that 40 Hz (gamma) stimulation (e.g., through light, sound, magnetic, or electrical stimulation sources) can improve episodic memory and learning, can facilitate neurogenesis, and can also reduce biomarkers associated with AD pathology including beta‐amyloid (Aβ) and tau. Although preliminary studies regarding the efficacy of gamma stimulation in humans has been promising, evidence is limited, neuroplastic changes are unclear, and the feasibility of electrical‐based gamma stimulation is still under investigation. Here, we aimed to characterize feasibility and neuroplastic changes associated with possible improvements in episodic memory following electrical non‐invasive neurostimulation.Method13 individuals with aMCI received eight 60‐minute sessions of 40‐Hz (gamma) transcranial alternating current stimulation (tACS), in a single‐arm design. Primary outcomes assessed side‐effects and drop‐out as indicators of feasibility. Secondary outcomes included episodic memory, plasma‐based Aβ and tau. Exploratory measures included neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and white matter fractional anisotropy. Additionally, neuroplastic changes were characterized by resting state functional connectivity (RSFC) within an episodic memory network and neuronal excitatory/inhibitory (Glx/GABA) balance via magnetic resonance spectroscopy.ResultResults revealed that gamma tACS was feasible (minimal side effects and no drop‐outs due to tACS). Moreover, aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in Aβ, tau, NfL, or GFAP. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS‐induced electric fields and exhibited the greatest changes in RSFC – all within an episodic memory network. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity across numerous tracts.ConclusionThis study highlights the potential of gamma tACS to improve episodic memory in an aMCI population by modulating functional connectivity and excitability within an episodic memory network.