Exploring Salivary Brain-Derived Neurotrophic Factor (BDNF) as a Potential Biomarker of Neuroplasticity in Older Adults Through Exergaming

Background Dementia and late-life depression (LLD) are common among older adults and are often associated with cognitive decline. Exergaming, which integrates physical and cognitive stimulation, may promote neuroplasticity in this population. Noninvasive biomarkers, such as salivary brain-derived neurotrophic factor (BDNF) methylation, provide a novel approach for monitoring intervention-related neuroplastic changes. Objective This pilot study examined the feasibility of a four-week exergaming intervention aimed at promoting both cognitive and physical engagement in older adults with dementia or LLD. The study also assessed changes in salivary BDNF DNA methylation, a biomarker of neuroplasticity, using noninvasive collection and droplet digital PCR (ddPCR) analysis. Results Participants engaged meaningfully in the exergame, and cognitive metrics showed improved performance across sessions. BDNF methylation was detectable in saliva samples, confirming feasibility; however, the small sample size and limited statistical power precluded significant findings. No causal conclusions can be drawn. Conclusions This study demonstrates that exergaming, combined with saliva collection and ddPCR, is both feasible and acceptable for older adults with cognitive impairment or depression. The intervention design was informed by theoretical frameworks of neuroplasticity, motor learning, and task-specific training. Larger controlled studies are warranted to evaluate clinical efficacy, expand BDNF analyses, and further investigate underlying neuroplastic mechanisms.