Augmenting cognitive training in older adults (The ACT Study): Design and Methods of a Phase III tDCS and cognitive training trial

Abstract

Background: Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT).

Methods: ACT will enroll 360 participants aged 65 to 89 with age-related cognitive decline, but not dementia. Participants will undergo cognitive training intervention or education training-control combined with tDCS or sham tDCS control. Cognitive training employs a suite of eight adaptive training tasks focused on attention/speed of processing and working memory from Posit Science BrainHQ. Training control involves exposure to educational nature/history videos and related content questions of the same interval/duration as the cognitive training. Participants are assessed at baseline, after training (12weeks), and 12-month follow-up on our primary outcome measure, NIH Toolbox Fluid Cognition Composite Score, as well as a comprehensive neurocognitive, functional, clinical and multimodal neuroimaging battery.

Significance: The findings from this study have the potential to significantly enhance efforts to ameliorate cognitive aging and slow dementia.

Keywords: Adaptive randomized clinical trial design; Aging; Cognitive training; Phase III; Transcranial direct current stimulation; tDCS.

Figure 1

ACT Conceptual Model. Cognitive training holds promise for reducing the adverse effects of cognitive aging, enhancing neuroplasticity, cognitive efficiency, functional capacity, and quality of life. In theory, coupling cognitive training with an intervention that increases neuroplasticity (e.g., tDCS) could augment training outcomes. We hypothesize that CT leads to improvements in neuroplasticity (GABA MRS) and functional brain response (FMRI). In turn this can lead to improved cerebral metabolic health and structural brain preservation. Coupling cognitive training with tDCS will increase neuroplasticity in brain areas important for working memory, focused attention/executive attention, and processing speed, improve effectiveness of cognitive training, and ultimately cognitive health and functional abilities.

Figure 2

ACT Cell Design. A) Phase 1 four-cell design (n=80). B) Phase 2 two-cell design (n=280). CT = cognitive training, TC = education training control, tDCS = transcranial direct current stimulation, Sham = sham tDCS.

Figure 3

ACT Study Design. Figure depicts time points of contact, randomization, intervention, and assessment for ACT participants.

Figure 4

The Education Training Control video menu. Participants randomized to the education training condition use this menu to select their daily videos during the intervention phase of the trial.

Figure 5

N-Back fMRI Task. An example of N-Back working memory stimuli presented to participants in scanner. Participants are presented with a fixation crosshair followed by a consonant on the screen and required to determine whether the letter was either an ‘X’ in the 0-Back paradigm or the same as the letter presented “2-back” in the 2-Back paradigm.

Figure 6

Useful-Field-of-View (UFOV)/Double Decision fMRI Task. An example of a single trial of the UFOV/Double Decision fMRI task. Participants are presented with a fixation crosshair followed by stimulus display where they are required to remember the central presented car or truck and the location of a peripherally presented car amongst a varied level of distractors in the shape of a yield sign. Participants then view a visual mask image to interfere with retinal images created by the prior stimulus and finally response screen that depicts a car or truck in the center box and a car in a location on the periphery. Participants respond yes/no indicating if the response screen matches the stimulus screen.