TY - JOUR
T1 - Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease
AU - Brem, A.-K.
AU - Di Iorio, R.
AU - Fried, P.J.
AU - Oliveira-Maia, A.J.
AU - Marra, C.
AU - Profice, P.
AU - Quaranta, D.
AU - Schilberg, L.
AU - Atkinson, N.J.
AU - Seligson, E.E.
AU - Rossini, P.M.
AU - Pascual-Leone, A.
N1 - Export Date: 29 January 2021
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.3389/fnagi.2020.00200
DO - 10.3389/fnagi.2020.00200
M3 - Article
VL - 12
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
ER -