Augmenting cognitive training in older adults with transcranial direct current stimulation: Initial results from the Phase III ACT trial and new directions

Background: Effective non-pharmacological interventions to remediate age-related cognitive decline and alter trajectories toward dementia are limited. The Augmenting Cognitive Training in Older Adults trial (ACT) was the first phase III randomized clinical trial initiated for transcranial direct current stimulation. Method: This NIA funded trial sought to evaluate whether 3 months of cognitive training paired with bilateral 2mA tDCS to the frontal lobes could produce clinically meaningful improvement in a composite measure of cognitive function in healthy older adults: the NIH Toolbox Fluid Cognition Composite score. The ACT trial will be unblinded April 30, 2022. Further still, over the past 5 years, it has become increasingly evident that fixed dosing approaches to tDCS, like those used in the ACT and every other trial to date, are insufficient for addressing individual differences and maximizing clinical outcomes. Results: We will present, for the first time, the primary outcome results from the ACT trial. In addition, we will present initial findings from related secondary neuroimaging and cognitive indices. In this talk, we will also present preliminary findings from our ongoing work to refine dosing technology for tDCS in older adults using computational modeling, artificial intelligence and multimodal imaging, paired with tDCS outcomes from the ACT trial. Conclusion: We will present new analyses, available only upon unblinding of ACT. These data use person-specific computational models of tDCS current flow paired with machine learning and clinical outcomes to identify critical characteristics of tDCS current in the brain (e.g., intensity, direction of current flow) most strongly associated with response vs. non-response. These data will provide initial insight into which regions of the brain and what characteristics of current were strongly associated with treatment response in the ACT trial. In addition, these data also provide critical insight into how stimulation dosing (electrode positioning, stimulation intensity) can be modified at a person-specific level to potentially enhance clinical outcomes. Thus, the proposed talk will provide state of the art trial findings from the first completed tDCS Phase III clinical trial paired with next generation approaches to remediated age-related cognitive decline using tDCS technology.