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000267053 1001_ $$aAntonenko, Daria$$b0
000267053 245__ $$aCognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial.
000267053 260__ $$aLondon$$bBioMed Central$$c2024
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000267053 520__ $$aRepeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks.In our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60-80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample.For the primary outcome, no difference was observed in the ITT (β = 0.1, 95%-CI [- 1.2, 1.3, p = 0.93] or PP sample (β = - 0.2, 95%-CI [- 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, β = 5.0, 95%-CI [- 0.1, 10.2], p = 0.06, d-prime β = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, β = 3.0, 95%-CI [- 3.9, 9.9], p = 0.39, d-prime β = 0.1, 95%-CI [- 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (pFDR < 0.05). Exploratory analyses showed a correlation between individual memory improvements and higher electric field magnitudes induced by tDCS (ρtDCS = 0.59, p = 0.02). Adverse events did not differ between groups, questionnaires indicated successful blinding (incidence rate ratio, 1.1, 95%-CI [0.5, 2.2]).In sum, cognitive training with concurrent brain stimulation, compared to cognitive training with sham stimulation, did not lead to superior performance enhancements in patients with cognitive impairment. However, we observed transferred working memory benefits in patients who underwent the full 3-week intervention. MRI data pointed toward a potential intervention-induced modulation of neural network dynamics. A link between individual performance gains and electric fields suggested dosage-dependent effects of brain stimulation. Together, our findings do not support the immediate benefit of the combined intervention on the trained function, but provide exploratory evidence for transfer effects on working memory in patients with cognitive impairment. Future research needs to explore whether individualized protocols for both training and stimulation parameters might further enhance treatment gains.The study is registered on ClinicalTrials.gov (NCT04265378). Registered on 7 February 2020. Retrospectively registered.
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000267053 650_7 $$2Other$$aElectric field simulation
000267053 650_7 $$2Other$$aMild cognitive impairment
000267053 650_7 $$2Other$$aResting-state functional connectivity
000267053 650_7 $$2Other$$aSubjective cognitive decline
000267053 650_7 $$2Other$$aTranscranial direct current stimulation
000267053 650_2 $$2MeSH$$aHumans
000267053 650_2 $$2MeSH$$aTranscranial Direct Current Stimulation: methods
000267053 650_2 $$2MeSH$$aCognitive Training
000267053 650_2 $$2MeSH$$aMemory, Short-Term: physiology
000267053 650_2 $$2MeSH$$aCognitive Dysfunction: therapy
000267053 650_2 $$2MeSH$$aDouble-Blind Method
000267053 650_2 $$2MeSH$$aBrain
000267053 650_2 $$2MeSH$$aPrefrontal Cortex
000267053 7001_ $$aFromm, Anna Elisabeth$$b1
000267053 7001_ $$aThams, Friederike$$b2
000267053 7001_ $$aKuzmina, Anna$$b3
000267053 7001_ $$aBackhaus, Malte$$b4
000267053 7001_ $$aKnochenhauer, Elena$$b5
000267053 7001_ $$aLi, Shu-Chen$$b6
000267053 7001_ $$aGrittner, Ulrike$$b7
000267053 7001_ $$0P:(DE-2719)2812683$$aFlöel, Agnes$$b8$$eLast author$$udzne
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