Towards a neurophysiological diagnostic marker of Alzheimer's disease using transcranial magnetic stimulation combined with electroencephalography

Ben-Hayun R, Zifman N, Hadad R, Fogel H, Levy-Lamdan O, Verhovski N, Yarovinsky N, Ayoub-Agbaria R, Tanne D

Key finding

P30 amplitude after left motor cortex stimulation was higher in biomarker-confirmed Alzheimer's disease than in controls and in other causes of cognitive impairment.

Study design

Clinical study, TMS-EEG with Delphi-MD™

Participants

90 participants: 22 biomarker-confirmed AD, 27 other cognitive impairment, 41 controls

Summary

A scalable, objective measure of cortical function that separates Alzheimer's disease (AD) from other causes of cognitive impairment is still lacking. This study tested whether the P30 amplitude, recorded with TMS-EEG after stimulation of the left primary motor cortex (M1L), reflects AD-related changes in cortical excitability.

Study design

Participants: 90 in total, all assessed with M1L TMS-EEG using Delphi-MD™.
Groups: biomarker-confirmed AD (22), other cognitive impairment (27: vascular or mixed 12, frontotemporal dementia 4, unknown etiology 11) and cognitively normal controls (41).

Key findings

P30 amplitude differed across the three groups (p = 0.009).
P30 was higher in biomarker-confirmed AD than in other cognitive impairment (p = 0.037, d = 0.61) and than in controls (p = 0.002, d = 0.80).
Among 27 clinically suspected AD patients tested for biomarkers, P30 was higher in biomarker-positive (22) than biomarker-negative (5) patients (p = 0.035, d = 0.98), with an ROC of 0.853 (95% CI 0.627–1.000).
P30 was not associated with cerebrovascular changes (p = 0.455).

Authors' conclusions

The authors report that P30 amplitude is elevated in biomarker-confirmed AD, in line with amyloid-associated cortical hyperexcitability, and present it as a promising non-invasive physiological biomarker that may aid differential diagnosis and, potentially, disease monitoring in AD.

Read the full article

Ben-Hayun R, Zifman N, Hadad R, Fogel H, Levy-Lamdan O, Verhovski N, Yarovinsky N, Ayoub-Agbaria R, Tanne D. Towards a neurophysiological diagnostic marker of Alzheimer's disease using transcranial magnetic stimulation combined with electroencephalography. Journal of Alzheimer's Disease. 2026;112:1895–1903. doi:10.1177/13872877261463653

Summary prepared by QuantalX from the published abstract. All results are as reported by the authors. The full text is available from the publisher.

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