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Research paper
Transcranial magnetic stimulation predicts cognitive decline in patients with Alzheimer’s disease
  1. Caterina Motta1,2,
  2. Francesco Di Lorenzo1,2,
  3. Viviana Ponzo1,
  4. Maria Concetta Pellicciari1,
  5. Sonia Bonnì1,
  6. Silvia Picazio1,
  7. Nicola Biagio Mercuri2,
  8. Carlo Caltagirone1,2,
  9. Alessandro Martorana1,2,
  10. Giacomo Koch1,3
  1. 1 Non Invasive Brain Stimulation Unit, Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy
  2. 2 Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
  3. 3 Stroke Unit, Tor Vergata Policlinic, Rome, Italy
  1. Correspondence to Dr Giacomo Koch, Non Invasive Brain Stimulation Unit, Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Fondazione S. Lucia, Rome 00179, Italy; g.koch{at}


Objective To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in patients with Alzheimer’s disease (AD) and predicting cognitive decline since the early phases of the disease.

Methods We used TMS-based parameters to evaluate long-term potentiation (LTP)-like cortical plasticity and cholinergic activity as measured by short afferent inhibition (SAI) in 60 newly diagnosed patients with AD and 30 healthy age-matched subjects (HS). Receiver operating characteristic (ROC) curves were used to assess TMS ability in discriminating patients with AD from HS. Regression analyses examined the association between TMS-based parameters and cognitive decline. Multivariable regression model revealed the best parameters able to predict disease progression.

Results Area under the ROC curve was 0.90 for LTP-like cortical plasticity, indicating an excellent accuracy of this parameter in detecting AD pathology. In contrast, area under the curve was only 0.64 for SAI, indicating a poor diagnostic accuracy. Notably, LTP-like cortical plasticity was a significant predictor of disease progression (p=0.02), while no other neurophysiological, neuropsychological and demographic parameters were associated with cognitive decline. Multivariable analysis then promoted LTP-like cortical plasticity as the best significant predictor of cognitive decline (p=0.01). Finally, LTP-like cortical plasticity was found to be strongly associated with the probability of rapid cognitive decline (delta Mini-Mental State Examination score ≤−4 points at 18 months) (p=0.04); patients with AD with lower LTP-like cortical plasticity values showed faster disease progression.

Conclusions TMS-based assessment of LTP-like cortical plasticity could be a viable biomarker to assess synaptic impairment and predict subsequent cognitive decline progression in patients with ADs.

  • TMS
  • clinical progression
  • AD
  • plasticity

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  • CM and FDL contributed equally.

  • Contributors Study concept and design: FDL, GK. Acquisition, analysis or interpretation of data: CM, FDL, VP, SB, MCP. Drafting of the manuscript: CM, FDL, AM, GK. Manuscript revision: CM, FDL, NBM, CC, AM, GK. Statistical analysis: CM, FDL. Study supervision: CC, AM, GK. 

  • Funding This study was funded by the Italian Ministry of Health (grant no. RF-2010-2311484).

  • Competing interests None declared.

  • Patient consent Parental/guardian consent obtained. 

  • Ethics approval Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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