Brain connectivity correlates of the impact of a digital intervention for individuals with subjective cognitive decline on depression and IL-18

Late-life depression represents a significant health concern, linked to disruptions in brain connectivity and immune functioning, mood regulation, and cognitive function. This pilot study explores a digital intervention targeting mental health, brain health, and immune functioning in individuals aged 55-60 with subjective cognitive decline, elevated stress and depressive symptoms. Seventeen participants engaged in a two-week intervention comprising spatial cognition, psychological techniques based on mindfulness, attention-training exercises, and cognitive behavioral therapy. Pre-and post-intervention changes in resting-state functional connectivity, inflammation, and psychological health were evaluated. Key findings include: (1) Reduced self-reported depression with a large effect size, (2) Decreased connectivity within the default mode network (DMN), (3) Enhanced anticorrelation between the DMN-Salience networks that was associated with improved depression scores (4) Reduced salivary IL-18 concentration with a medium effect size, correlated with decreased DMN-amygdala connectivity. There was a trend towards reduced anxiety, with no significant changes in quality of life. To our knowledge, this is the first study to investigate the effect of digital intervention on immune markers, clinical behavioral outcomes, and brain function, demonstrating positive synergistic potential across all three levels. These preliminary findings, which need replication in larger, controlled studies, have important implications for basic science and scalable digital interventions.