Randomized trial of cognitive training and brain stimulation in non‐demented older adults

Abstract

Introduction Given rapid global population aging, developing interventions against age‐associated cognitive decline is an important medical and societal goal. We evaluated a cognitive training protocol combined with transcranial direct current stimulation (tDCS) on trained and non‐trained functions in non‐demented older adults. Methods Fifty‐six older adults (65–80 years) were randomly assigned to one of two interventional groups, using age and baseline performance as strata. Both groups performed a nine‐session cognitive training over 3 weeks with either concurrent anodal tDCS (atDCS, 1 mA, 20 minutes) over the left dorsolateral prefrontal cortex (target intervention) or sham stimulation (control intervention). Primary outcome was performance on the trained letter updating task immediately after training. Secondary outcomes included performance on other executive and memory (near and far transfer) tasks. All tasks were administered at baseline, post‐intervention, and at 1‐ and 7‐month follow‐up assessments. Prespecified analyses to investigate treatment effects were conducted using mixed‐model analyses. Results No between‐group differences emerged in the trained letter updating and Markov decision‐making tasks at post‐intervention and at follow‐up timepoints. Secondary analyses revealed group differences in one near‐transfer task: Superior n‐back task performance was observed in the tDCS group at post‐intervention and at follow‐up. No such effects were observed for the other transfer tasks. Improvements in working memory were associated with individually induced electric field strengths. Discussion Cognitive training with atDCS did not lead to superior improvement in trained task performance compared to cognitive training with sham stimulation. Thus, our results do not support the immediate benefit of tDCS‐assisted multi‐session cognitive training on the trained function. As the intervention enhanced performance in a near‐transfer working memory task, we provide exploratory evidence for effects on non‐trained working memory functions in non‐demented older adults that persist over a period of 1 month.

Microstructural and functional plasticity following repeated brain stimulation during cognitive training in non-demented older adults

“…Corroborating and extending these and previous ndings, we here showed that the functional coupling between bilateral prefrontal regions -part of the frontoparietal network -was increased through tDCS, suggesting that enhanced temporal coherence of BOLD activity is one of the mechanisms underlying tDCS effects. By enabling more coordinated/synchronized activity between network hubs, tDCS combined with repeated sessions may produce (potentially longer-term) transfer effects 2,15,25,50 . In our data, we did not observe an association between FC changes and behavioral performance gains, pointing to a rather complex relationship which may also be masked by the impact of baseline FC on behavioral modulation 51,52 .…”

“…All participants were right-handed, native German speakers, had no history of neurological or severe psychiatric diseases, did not take any central nervous system active medication, and performed within age-and education-adjusted normative range in the neuropsychological screening (Consortium to Establish a Registry for Alzheimer's Disease, CERAD-Plus Test Battery, https://www.memoryclinic.ch). All participants completed the TrainStim-Cog clinical study where they received anodal or sham transcranial direct current stimulation over the left prefrontal cortex during three weeks (totaling up to nine sessions) of a training of two executive functions tasks (a letter updating task and a value-based Markov decision making task 25,26 , NCT03838211, https://clinicaltrials.gov/show/NCT03838211). All behavioral data is reported in 25 .…”

“…All participants completed the TrainStim-Cog clinical study where they received anodal or sham transcranial direct current stimulation over the left prefrontal cortex during three weeks (totaling up to nine sessions) of a training of two executive functions tasks (a letter updating task and a value-based Markov decision making task 25,26 , NCT03838211, https://clinicaltrials.gov/show/NCT03838211). All behavioral data is reported in 25 . In the present study, we analysed the magnetic resonance (MR) imaging data acquired in 48 participants -including resting-state functional MR imaging, structural T1 imaging, and diffusion tensor imaging (DTI) -before and immediately after the three-week intervention.…”

Review of individualized current flow modeling studies for transcranial electrical stimulation

“…A cognitive training study with a group of elderly participants did not show an expected effect of tDCS on task performance when applying a protocol with 1 mA current intensity, derived from studies with young participants (Antonenko et al, 2022). The authors indicate signs of atrophy in their retrospectively analyzed head models for current flow modeling and indicated the missing correction for effective electric field strength as a compromising factor on the stimulation results.…”

Facilitatory stimulation of the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity

“…Similar to the use of NIBS to boost neuropsychological rehabilitation after disruption of function due to stroke, these techniques might have the potential to support preservation of cognitive functions in pathological but also healthy aging through modulation of cortical excitability and the enhancement of neuroplasticity (Hartwigsen, 2018, 2015; Siebner et al, 2009). While there are some first promising results from different cognitive domains (for reviews, see Booth et al, 2022; Goldthorpe et al, 2020; Hsu et al, 2015), particularly when NIBS is coupled with training interventions, variability remains high and some studies find no beneficial effect of stimulation (e.g., Antonenko et al, 2022). Further insight into the potential of NIBS in aging can be gained by investigating the effect of stimulation on neural activity and functional connectivity.…”