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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00200

DOI=10.3389/fnagi.2020.00200

ISSN=1663-4365

ABSTRACT=<sec><title>Objective</title><p>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.</p></sec><sec><title>Methods</title><p>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 (<italic>n</italic> = 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 (<italic>n</italic> = 18) received sham rTMS combined with either real (sham/real group, <italic>n</italic> = 10) or sham (sham/sham group, <italic>n</italic> = 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).</p></sec><sec><title>Results</title><p>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.</p></sec><sec><title>Interpretation</title><p>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.</p></sec><sec><title>Clinical Trial Registration</title><p><ext-link ext-link-type="uri" xlink:href="http://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</ext-link>, identifier NCT01504958.</p></sec>