TY - JOUR
T1 - Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease
AU - Brem, Anna Katharine
AU - Di Iorio, Riccardo
AU - Fried, Peter J.
AU - Oliveira-Maia, Albino J.
AU - Marra, Camillo
AU - Profice, Paolo
AU - Quaranta, Davide
AU - Schilberg, Lukas
AU - Atkinson, Natasha J.
AU - Seligson, Erica E.
AU - Rossini, Paolo Maria
AU - Pascual-Leone, Alvaro
PY - 2020/7/8
Y1 - 2020/7/8
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.
KW - Alzheimer’s disease
KW - clinical trial
KW - cognitive training
KW - combinatory intervention
KW - plasticity
KW - randomized controlled
KW - transcranial magnetic stimulation
UR - http://www.scopus.com/inward/record.url?scp=85088423622&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2020.00200
DO - 10.3389/fnagi.2020.00200
M3 - Article
C2 - 32733232
AN - SCOPUS:85088423622
VL - 12
JO - FRONTIERS IN AGING NEUROSCIENCE
JF - FRONTIERS IN AGING NEUROSCIENCE
SN - 1663-4365
M1 - 200
ER -