Brain and cognitive changes in memory systems vulnerable to Alzheimer’s disease following targeted multiday repetitive transcranial magnetic stimulation applied to healthy young adults

Abstract Background Aging processes — healthy and pathological — contribute to age‐related memory decline, and current treatments offer limited remediation. Targeted non‐invasive brain stimulation (NBS) of memory networks vulnerable to Alzheimer’s disease is a novel approach which can enhance memory in healthy young adults by 20% (Wang et al., 2014). To test generalizability of this finding, we are administering a clinical trial (ClinicalTrials.gov #alz045244) applying targeted NBS to healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (aMCI). Here, we report preliminary findings from the trial arm studying healthy young adults. Method Our approach replicates methods from Wang et al. (2014). Healthy young adults (N = 16) completed two interventions which combined pre/post‐stimulation brain and cognitive measurement with NBS (treatment or sham for five consecutive days) in the form of repetitive transcranial magnetic stimulation (rTMS). The two interventions were identical except for rTMS parameters. Pre‐/post‐stimulation, brain measures included structural and resting‐state functional MRI data; cognitive measures included cognitive abilities (e.g., hippocampal‐dependent memory). Intervention formats applied rTMS using β‐frequency pulse sequences which alternated 2‐sec. 20 Hz stimulation with 28‐sec. rest for 20 min; the stimulation location was constant (left lateral parietal cortex coactive with a hippocampus‐centered network). Stimulation intensity was tailored to participants’ resting motor threshold (RMT) and varied by condition: treatment, 100% RMT; sham, 10% RMT. Participants completed both conditions in a counterbalanced order. Result We successfully mapped hippocampus‐centered functional networks in each participant and localized left lateral parietal targets for rTMS. Furthermore, we observed changes in brain and cognitive measures related to the stimulation condition. Brain measures including resting‐state functional connectivity (RSFC) revealed changes in patterns of RSFC between several areas of the hippocampus‐centered network targeted with rTMS in the treatment condition. Conclusion Our ongoing clinical trial measures changes in brain and cognitive variables associated with NBS of a functional brain network supporting memory. The current trial arm focused on healthy young adults, and we found evidence consistent with plasticity in the intrinsic brain network supporting memory. Findings from the remaining arms (older adults, healthy or aMCI) will inform the generalizability of our observations to populations vulnerable to Alzheimer’s disease.