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

Neurobiol Aging. 2021 Dec;108:24-33. doi: 10.1016/j.neurobiolaging.2021.06.007. Epub 2021 Jun 24.


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. The objective of this study was to investigate the association between a transcranial magnetic stimulation (TMS) measure of motor cortical excitability and measures of cognition in AD. A retrospective cross-sectional analysis tested 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-AD cohort (n=22, β=-.70, p<0.001) but not in the control cohort (n=26, β=-0.13, p=0.513). This relationship was confirmed in the validation-AD cohort (n=129, β=-.35, p<0.001). 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.

Keywords: Alzheimer's Disease Assessment Scale – Cognitive Subscale; Cognitive dysfunction; Cortical excitability; Dementia; Hyperexcitability; Neurophysiological marker; Resting motor threshold; Transcranial magnetic stimulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology*
  • Cognition*
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / physiopathology*
  • Cognitive Dysfunction / psychology
  • Cortical Excitability*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology*
  • Neuropsychological Tests
  • Retrospective Studies
  • Transcranial Magnetic Stimulation