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

doi:10.3389/fnagi.2020.00200

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

Front Aging Neurosci. 2020 Jul 8:12:200. doi: 10.3389/fnagi.2020.00200. eCollection 2020.

Authors

Anna-Katharine Brem^{1

2}, Riccardo Di Iorio³, Peter J Fried¹, Albino J Oliveira-Maia^{4

5

6}, Camillo Marra³, Paolo Profice³, Davide Quaranta³, Lukas Schilberg^{1

7}, Natasha J Atkinson¹, Erica E Seligson¹, Paolo Maria Rossini⁸, Alvaro Pascual-Leone^{9

10

11}

Affiliations

¹ Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
² Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
³ Department of Geriatrics, Neurosciences and Orthopaedics, Polyclinic A. Gemelli Foundation-IRCCS, Rome, Italy.
⁴ Champalimaud Research and Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal.
⁵ Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.
⁶ NOVA Medical School - Faculdade de Ciências Médicas de Lisboa, Universidade Nova de Lisboa, Lisbon, Portugal.
⁷ Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.
⁸ Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele, Rome, Italy.
⁹ Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston, MA, United States.
¹⁰ Department of Neurology, Harvard Medical School, Boston, MA, United States.
¹¹ Guttmann Brain Health Institut, Institut Guttmann, Universitat Autonoma Barcelona, Barcelona, Spain.

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.

Keywords: Alzheimer’s disease; clinical trial; cognitive training; combinatory intervention; plasticity; randomized controlled; transcranial magnetic stimulation.

Associated data

ClinicalTrials.gov/NCT01504958

Abstract

Associated data

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