Pre-Injury Adversity, Functional Recovery, and Salivary microRNA Changes After a Dual-Task Exercise in Asians and...

Background: Mild traumatic brain injury (mTBI) is frequently associated with persistent cognitive and psychosocial symptoms, yet biological correlates of recovery remain poorly understood, particularly among Asian and Pacific Islander (API) populations. Pre-injury psychosocial adversity may further shape post-injury recovery trajectories. This pilot study examined associations between participation in a 2-week, home-based, dual-task cognitive-walking intervention (Daily Brain Exercise; DBE) and changes in cognitive, psychological, and salivary microRNA (miRNAs) measures among APIs with and without a self-reported history of mTBI. Methods: API participants completed remote cognitive testing (CNS Vital Signs), psychosocial assessments (Neuro-QoL), and saliva collection before and after DBE participation. Salivary RNA was purified, and miRNA expression was profiled using nCounter^® Human v3 miRNA Expression Panels (NanoString). Differential expression analyses were conducted using ROSALIND^® platform (OnRamp Bioinformatics, San Diego, CA, USA), a cloud-based bioinformatics analysis system, to calculate fold changes and p-values. Pre-injury psychosocial adversity was assessed via the Trauma History Screen and examined descriptively as a contextual modifier of functional outcomes. Results: Twenty-one APIs (mean age 22.9 years; 76.7% female) were enrolled, including 14 individuals with a self-reported history of mTBI (mean 4.64 years post-injury; 50% with multiple injuries). Following DBE participation, increases in cognitive flexibility and executive function scores were observed in both mTBI and control groups. Additional increases in psychomotor speed, processing speed, sleep disturbance, and depressive symptoms were observed descriptively within the mTBI group. Subgroup analyses suggested variability in pre-post patterns across combinations of mTBI history and pre-injury psychosocial adversity. Exploratory miRNA analyses identified seven miRNAs that were differentially expressed in the mTBI group following DBE (unadjusted p < 0.005), including hsa-miR-7-5p, previously reported in association with neurodevelopmental and neurological pathways. Conclusions: In this pilot, feasibility-focused study, participation in a brief, home-based, dual-task intervention was associated with descriptive changes in selected cognitive and psychosocial measures among APIs, particularly those with a history of mTBI and pre-injury adversity. The observed subgroup patterns warrant confirmation in adequately powered, controlled studies. Exploratory changes in salivary miRNAs co-occurred with functional improvements, thus generating a hypothesis for a future investigation.