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@ARTICLE{Antonenko:267053,
      author       = {Antonenko, Daria and Fromm, Anna Elisabeth and Thams,
                      Friederike and Kuzmina, Anna and Backhaus, Malte and
                      Knochenhauer, Elena and Li, Shu-Chen and Grittner, Ulrike
                      and Flöel, Agnes},
      title        = {{C}ognitive training and brain stimulation in patients with
                      cognitive impairment: a randomized controlled trial.},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {16},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2024-00062},
      pages        = {6},
      year         = {2024},
      abstract     = {Repeated 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.},
      keywords     = {Humans / Transcranial Direct Current Stimulation: methods /
                      Cognitive Training / Memory, Short-Term: physiology /
                      Cognitive Dysfunction: therapy / Double-Blind Method / Brain
                      / Prefrontal Cortex / Electric field simulation (Other) /
                      Mild cognitive impairment (Other) / Resting-state functional
                      connectivity (Other) / Subjective cognitive decline (Other)
                      / Transcranial direct current stimulation (Other)},
      cin          = {AG Flöel},
      ddc          = {610},
      cid          = {I:(DE-2719)5000081},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10782634},
      pubmed       = {pmid:38212815},
      doi          = {10.1186/s13195-024-01381-3},
      url          = {https://pub.dzne.de/record/267053},
}