Evaluating Neurotrophins and Irisin in a Lifestyle Intervention Study for Dementia Risk Reduction

Background: The rising prevalence of Alzheimer's disease (AD) and related neurodegenerative disorders highlights the need for non-pharmacological strategies to preserve cognitive health. Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and irisin are biomarkers associated with cognitive resilience and metabolic health. Objective: To assess the impact of a multimodal lifestyle intervention on serum BDNF, VEGF, and irisin levels in an aging population, aiming to explore how modifiable lifestyle factors influence biomarkers linked to neurodegeneration risk. Methods: In a randomised controlled trial, participants were assigned to a 12-week lifestyle intervention group (n=42, 32 female; mean age 67.1±7.6 years) or a control group (n=41, 34 female; mean age 62.7±8.6 years). The intervention included structured physical exercise, dietary modifications, sleep hygiene, and mindfulness practices. Serum BDNF, VEGF, and irisin levels were measured at baseline (T1), post-intervention (T2), and six months post-intervention (T3). Linear mixed models assessed biomarker changes over time and between groups. Results: Irisin levels increased significantly post-intervention (T2) in the intervention group (p < 0.001) in comparison to the control group and were maintained at T3 (p = 0.003). The intervention group also exhibited a significant attenuation of BDNF decline at T3 compared to the control group (p = 0.007). VEGF levels remained stable across all time points (p > 0.05). Collectively, these changes suggest that the intervention resulted in positive metabolic and neuroprotective effects. Conclusion: A structured lifestyle intervention can significantly elevate BDNF and irisin levels, supporting non-pharmacological strategies to enhance brain health and potentially reduce neurodegeneration risk in older adults.