Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial

• Published in: Alzheimer's research & therapy 2024-01, Vol.16 (1), p.6-6, Article 6
• Main Authors: Antonenko, Daria, Fromm, Anna Elisabeth, Thams, Friederike, Kuzmina, Anna, Backhaus, Malte, Knochenhauer, Elena, Li, Shu-Chen, Grittner, Ulrike, Flöel, Agnes
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Brain; Clinical trials; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - therapy; Cognitive Training; Decision making; Dementia; Double-Blind Method; Electric field simulation; Electric fields; Humans; Intervention; Medical research; Memory; Memory, Short-Term - physiology; Mild cognitive impairment; Older people; Prefrontal Cortex; Resting-state functional connectivity; Subjective cognitive decline; Transcranial direct current stimulation; Transcranial Direct Current Stimulation - methods
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-024-01381-3

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 (p