Effects of a Multi-Session Cognitive Training Combined With Brain Stimulation (TrainStim-Cog) on Age-Associated Cognitive Decline – Study Protocol for a Randomized Controlled Phase IIb (Monocenter) Trial

Abstract

Background: With increasing aging populations worldwide, developing interventions against age-associated cognitive decline is particularly important. Evidence suggests that combination of brain stimulation with cognitive training intervention may enhance training effects in terms of performance gain or transfer to untrained domains. This protocol describes a Phase IIb clinical trial that investigates the intervention effects of training combined with brain stimulation in older adults. Methods: The TrainStim-Cog study is a monocentric, randomized, single-blind, placebo-controlled intervention. The study will investigate cognitive training with concurrent anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (target intervention) compared to cognitive training with sham stimulation (control intervention) over nine sessions in 3 weeks, consisting of a letter updating task, and a three-stage Markov decision-making task. Fifty-six older adults will be recruited from the general population. Baseline assessment will be performed including neuropsychological screening and performance on training tasks. Participants will be allocated to one of the two study arms using block-wise randomization stratified by age and baseline performance with a 1:1 allocation ratio. Primary outcome is performance in the letter updating task after training under anodal tDCS compared to sham stimulation. Secondary outcomes include performance changes in the decisionmaking task and transfer tasks, as well as brain structure and functional networks assessed by structural, and functional magnetic resonance imaging (MRI) that are acquired pre-and post-intervention.

Functional Effects of Bilateral Dorsolateral Prefrontal Cortex Modulation During Sequential Decision-Making: A Functional Near-Infrared Spectroscopy Study With Offline Transcranial Direct Current Stimulation

“…This finding is especially important in the light of the growing interest for repetitive cognitive trainings (with or without tDCS) aimed to counteract deficits in and enhance different cognitive functions (Park et al, 2014 ; Katz et al, 2017 ; Martin et al, 2017 ; Lawrence et al, 2018 ; Nissim et al, 2019 ), in particular sequential decision-making (Antonenko et al, 2019 ; Thams et al, 2020b ) in patients and older populations. fNIRS may allow cost- and time-effective monitoring of hemodynamic correlates of such interventions, aiming to improve their efficiency through repeated investigation and analysis of individual neural responsiveness.…”

“…Taken together, the current proof-of-concept results provide empirical evidence that fNIRS is a suitable cost-effective and non-invasive method to measure condition-dependent hemodynamic correlates (i.e., O 2 Hb, HHb, and tHb concentration changes) of sequential decision-making during a three-state Markov decision task irrespective of tDCS application. This finding is especially important in the light of the growing interest for repetitive cognitive trainings (with or without tDCS) aimed to counteract deficits in and enhance different cognitive functions (Park et al, 2014;Katz et al, 2017;Martin et al, 2017;Lawrence et al, 2018;Nissim et al, 2019), in particular sequential decision-making (Antonenko et al, 2019;Thams et al, 2020b) in patients and older populations. fNIRS may allow cost-and time-effective monitoring of hemodynamic correlates of such interventions, aiming to improve their efficiency through repeated investigation and analysis of individual neural responsiveness.…”

No Effect of Anodal tDCS on Verbal Episodic Memory Performance and Neurotransmitter Levels in Young and Elderly Participants

“…However, to ensure that the applied electric current arrives at the identified target region, older participants may require different electrode arrangements to compensate for altered current density distributions owing to brain atrophy accumulated during ageing [ 89 , 94 ]. Even more promising than adjustments of electrodes might be the repeated application of tDCS within a single session [ 95 ] or over several days [ 96 ]. Apart from enhancing the immediate effect of the stimulation due to the consolidation of changes in neuroplasticity, this procedure is also known to produce longer-lasting cognitive gains up to several months [ 97 ], which in turn increases the value of the treatment in a clinical setting.…”

Intensity dependent effect of cognitive training on motor cortical plasticity and cognitive performance in humans

“…While this intensity-dependent effect of cognitive training on PAS-induced plasticity is of importance with regard to clinical application of cognitive training interventions, e.g. against age-related cognitive decline or in neurorehabilitation (Antonenko et al 2018 ; Antonenko et al 2019 ; Bherer 2015 ), it is at the same time not straight-forward to interpret and necessitates further investigations.…”