Higher motor cortical excitability linked to greater cognitive dysfunction in Alzheimer's disease: results from two independent cohorts

Abstract

Prior studies have reported increased cortical excitability in people with Alzheimer's disease (AD), but findings have been inconsistent, and how excitability relates to dementia severity remains incompletely understood. We tested the association between transcranial magnetic stimulation (TMS) measure of motor cortical excitability and cognition in AD. A retrospective cross-sectional analysis investigated the relationship between resting motor threshold (RMT) and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) across two independent samples of AD participants (a discovery cohort, n=22 and a larger validation cohort, n=129) and a control cohort of cognitively normal adults (n=26). RMT was correlated with ADAS-Cog in the discovery cohort (n=22, β=-.70, p<.001) but not in the control cohort (n=26, β=-0.13, p=.513). This relationship was confirmed in the validation cohort (n=129, β=-.35, p<.001). RMT can be a useful neurophysiological marker of progressive global cognitive dysfunction in AD. Future translational research should focus on the potential of RMT to predict and track individual pathophysiological trajectories of aging.