Improving Neurological Health in Aging Via Neuroplasticity-Based Computerized Exercise: Protocol for a Randomized Controlled Trial (Preprint)

Abstract

BACKGROUND Our mechanistic understanding of how computerized brain training drives cognitive and functional benefit is 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 two computerized programs change acetylcholine expression, cognitive performance, and behavior 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 older adults aged 65+ are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control of computer games designed for entertainment (e.g., Solitaire). Each intervention includes 30-minutes of training per session with 7 sessions per week over a 10-week intervention period (35 total hours) completed remotely at home on either a loaned or personal device. The primary outcome is the change in FEOBV binding assessed at baseline and post-test. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine status are measured pre, post, and at a 3-month no-contact follow-up to evaluate maintenance of observed effects. RESULTS The study was approved by the Western IRB and REB of McGill University Health Centre. The trial is currently ongoing. The first participant was enrolled July 2021, recruitment completed in December 2023, and the trial will conclude in May 2024. CONCLUSIONS There is an unmet need to identify efficacious, inexpensive, and scalable non-pharmaceutical interventions to enhance cognition in older adults across the lifespan. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit. CLINICALTRIAL ClinicalTrials.gov NCT04149457 (registered on Nov 4 2019); https://clinicaltrials.gov/ct2/show/NCT04149457