Background: Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling. Objective: INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET). Methods: In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects. Results: The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024. Conclusions: There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit.
Background: Executive function encompasses a set of higher-order cognitive processes, including planning, cognitive flexibility, and inhibitory control, that are essential for goal-directed behavior. These abilities are adversely affected by age with executive dysfunction ultimately impairing performance on activities of daily living. Objective: This study aimed to assess the validity of a computerized cognitive assessment in predicting executive function performance in healthy older adults. Methods: This retrospective analysis utilized baseline data from the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial. The study provides normative data for cognitively healthy older adults (aged 65 years and above) and evaluates the usability and validity of Freeze Frame, a cognitive assessment available on the BrainHQ platform. Performance on Freeze Frame was analyzed in relation to self-reported demographic variables and neuropsychological function, using a standardized measure of executive function, the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH EXAMINER). Results: The intent-to-treat analysis included 92 cognitively healthy older adults (mean age = 71.9 years, SD = 4.86, range: 65–83), of whom 66% were female (61/92), with a mean education level of 16.45 years (SD = 3.40, range: 9–27). Performance on Freeze Frame was modestly associated with executive function scores on NIH EXAMINER (P = .019), accounting for 6.8% of the variance. The assessment showed a small but statistically significant relationship to age (ρ = -0.22, P = .046) and gender, with no significant influence of education. Psychometric evaluation supported its usability, with an average completion time of 4 minutes (SD = 0.16). Conclusions: Freeze Frame is a brief, scalable, and accessible computerized cognitive assessment with demonstrated concurrent validity for executive function. Its efficiency and ease of administration across internet-connected devices suggests potential applications for cognitive screening. Future research should explore its utility in detecting executive dysfunction in clinical populations and its potential role in predicting functional performance across activities of daily living. Clinical Trial: The study was registered on November 4, 2019 before participant enrollment under the name “Improving Neurological Health in Aging Via Neuroplasticity-based Computerized Exercise (INHANCE)” with identification number NCT04149457. See https://clinicaltrials.gov/study/NCT04149457 for details.