Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease

Anna Katharine Brem, Riccardo Di Iorio, Peter J. Fried, Albino J. Oliveira-Maia, Camillo Marra, Paolo Profice, Davide Quaranta, Lukas Schilberg, Natasha J. Atkinson, Erica E. Seligson, Paolo Maria Rossini, Alvaro Pascual-Leone

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Abstract

Objective: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer’s disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment. Methods: In this randomized, sham-controlled, multicenter clinical trial, 34 patients with AD were assigned to three experimental groups receiving 30 daily sessions of combinatory intervention. Participants in the real/real group (n = 16) received 10 Hz repetitive transcranial magnetic stimulation (rTMS) delivered separately to each of six cortical regions, interleaved with computerized cognitive training. Participants in the sham rTMS group (n = 18) received sham rTMS combined with either real (sham/real group, n = 10) or sham (sham/sham group, n = 8) cognitive training. Effects of treatment on neuropsychological (primary outcome) and neurophysiological function were compared between the 3 treatment groups. These, as well as imaging measures of brain atrophy, were compared at baseline to 14 healthy controls (HC). Results: At baseline, patients with AD had worse cognition, cerebral atrophy, and TMS measures of cortico-motor reactivity, excitability, and plasticity than HC. The real/real group showed significant cognitive improvement compared to the sham/sham, but not the real/sham group. TMS-induced plasticity at baseline was predictive of post-intervention changes in cognition, and was modified across treatment, in association with changes of cognition. Interpretation: Combined rTMS and cognitive training may improve the cognitive status of AD patients, with TMS-induced cortical plasticity at baseline serving as predictor of therapeutic outcome for this intervention, and potential mechanism of action. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01504958.

Original languageEnglish
Article number200
JournalFRONTIERS IN AGING NEUROSCIENCE
Volume12
DOIs
Publication statusPublished - 8 Jul 2020

Keywords

  • Alzheimer’s disease
  • clinical trial
  • cognitive training
  • combinatory intervention
  • plasticity
  • randomized controlled
  • transcranial magnetic stimulation

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