Brain Longevity: Extending cognitive life through integrated Neurofeedback Plus therapy and vagal stimulation. Randomized, controlled and multicenter clinical trial

This randomized, controlled, longitudinal, and multicenter clinical trial investigated the effectiveness of an integrated neurotechnology intervention – Neurofeedback Plus – in supporting cognitive longevity in clinically healthy older adults (60–70 years) by optimizing the functioning of the central and autonomic nervous system. Two hundred participants were randomly assigned to two groups: experimental (n = 100), which received 90 multimodal intervention sessions (EEG neurofeedback, gamma brain photobiomodulation, HRV biofeedback, non-invasive vagal stimulation) conducted in three therapeutic cycles for 12 months; and control group (n = 100), passively monitored. Assessments were performed at four time points (T0, T1, T2, T3), using validated markers: qEEG (global coherence, regional activation), HRV (RMSSD, SDNN, LF/HF), GP-8 (physiological stress) score, and heart-brain coherence biofeedback. Compared to the control group, the experimental group had statistically and clinically significant changes between T0 and T3: RMSSD (+12.8 vs. +2.1), SDNN (+9.2 vs. +1.5), LF/HF (–1.4 vs. –0.2), GP-8 score (-17.6 vs. – 2.8), EEG coherence (+15.2% vs. +3.1%). The interaction effect (Time x Group) was confirmed by the two-way ANOVA (p<0.01) Effect size (Cohen's d > 1.6) and multiple regression analyses indicated belonging to the experimental group as the strongest predictor. Post-hoc statistical power was 1.0 in all cases. The intervention of Neurofeedback Plus produces robust, multisystemic, and lasting effects on brain activity, autonomic regulation, and physiological stress, supporting the strengthening of neuroplasticity and cognitive resilience. The protocol is standardizable, clinically applicable and scalable in the context of public health, providing an innovative preventive solution for maintaining cognitive performance in old age.