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

• Published in: Neurobiology of aging Vol. 108; pp. 24 - 33
• Main Authors: Zadey, Siddhesh, Buss, Stephanie S., McDonald, Katherine, Press, Daniel Z., Pascual-Leone, Alvaro, Fried, Peter J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2021
• Subjects: Aged; Alzheimer Disease - complications; Alzheimer Disease - diagnosis; Alzheimer Disease - physiopathology; Alzheimer Disease - psychology; Alzheimer's Disease Assessment Scale – Cognitive Subscale; Cognition; Cognitive dysfunction; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cognitive Dysfunction - psychology; Cortical Excitability; Cross-Sectional Studies; Dementia; Female; Humans; Hyperexcitability; Male; Middle Aged; Motor Cortex - physiopathology; Neurophysiological marker; Neuropsychological Tests; Resting motor threshold; Retrospective Studies; Transcranial Magnetic Stimulation; Transcranial magnetic stimulation; AD; ADAS-Cog; Cortical excitability; CMS; Neurophysiological marker; CN; CSTS; Resting motor threshold; SCD; MMSE; Hyperexcitability; RMT; Alzheimer's Disease Assessment Scale – Cognitive Subscale; TMS; Cognitive dysfunction; Dementia
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.06.007

•We tested association of TMS-RMT (motor cortical excitability) with cognition in two AD cohorts.•Lower RMT was correlated with greater cognitive dysfunction in mild-to-moderate AD.•RMT was associated with memory function in AD and control groups.•RMT can be a useful noninvasive neurophysiological marker of AD cognitive dysfunction. 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.