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Neuronavigated Magnetic Stimulation combined with cognitive training for Alzheimer’s patients: an EEG graph study

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly subjects. Recent studies verified the effects of cognitive training combined with repetitive transcranial magnetic stimulation (rTMS-COG) in AD patients. Here, we analyzed neuropsychological and neurophysiological data, derived from electroencephalography (EEG), to evaluate the effects of a 6-week protocol of rTMS-COG in 72 AD. We designed a randomized, double-blind, sham-controlled trial to evaluate efficacy of rTMS on 6 brain regions obtained by an individual MRI combined with COG related to brain areas to stimulate (i.e., syntax and grammar tasks, comprehension of lexical meaning and categorization tasks, action naming, object naming, spatial memory, spatial attention). Patients underwent neuropsychological and EEG examination before (T0), after treatment (T1), and after 40 weeks (T2), to evaluate the effects of rehabilitation therapy. “Small World” (SW) graph approach was introduced allowing us to model the architecture of brain connectivity in order to correlate it with cognitive improvements. We found that following 6 weeks of intensive daily treatment the immediate results showed an improvement in cognitive scales among AD patients. SW present no differences before and after the treatment, whereas a crucial SW modulation emerges at 40-week follow-up, emphasizing the importance of rTMS-COG rehabilitation treatment for AD. Additional results demonstrated that the delta and alpha1 SW seem to be diagnostic biomarkers of AD, whereas alpha2 SW might represent a prognostic biomarker of cognitive recovery. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression, and rTMS-COG can be regarded as a potentially useful treatment for AD.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

This work was partially supported by the Italian Ministry of Health for Institutional Research (Ricerca corrente) and for the project “NEUROMASTER: NEUROnavigated MAgnetic STimulation in patients with mild-moderate Alzheimer disease combined with Effective cognitive Rehabilitation” (GR-2013- 510 02358430) and by Toto Holding. The authors are also grateful to the Merck Sharp & Dohme (MSD) for the sponsorship.

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Authors and Affiliations

  1. Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele Roma, Via Val Cannuta, 247, 00166, Rome, Italy

    Fabrizio Vecchio, Francesca Miraglia, Chiara Pappalettera & Paolo Maria Rossini

  2. Department of Theoretical and Applied Sciences, eCampus University, Novedrate, Como, Italy

    Fabrizio Vecchio, Francesca Miraglia & Chiara Pappalettera

  3. Neurology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Rome, Italy

    Davide Quaranta, Riccardo Di Iorio, Federica L’Abbate & Camillo Marra

  4. Neuropsychology Unit, IRCCS Istituto Centro San Giovanni Di DioFatebenefratelli, Brescia, Italy

    Maria Cotelli

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  1. Fabrizio Vecchio
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  2. Davide Quaranta
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  3. Francesca Miraglia
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  4. Chiara Pappalettera
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  6. Federica L’Abbate
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  7. Maria Cotelli
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  8. Camillo Marra
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  9. Paolo Maria Rossini
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Contributions

FV contributed to conceptualization, methodology, writing—original draft preparation; DQ and FM helped in supervision, writing—reviewing and editing; CP, RD, FL, MC, and CM were involved in methodology data curation, writing—reviewing and editing; PMR wrote and edited the review.

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Correspondence to Fabrizio Vecchio.

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Vecchio, F., Quaranta, D., Miraglia, F. et al. Neuronavigated Magnetic Stimulation combined with cognitive training for Alzheimer’s patients: an EEG graph study. GeroScience 44, 159–172 (2022). https://doi.org/10.1007/s11357-021-00508-w

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  • DOI: https://doi.org/10.1007/s11357-021-00508-w

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