Exercise-associated changes in leptin and irisin relate to cognitive function in older adults stratified by cognitive impairment.

Age-related cognitive decline and cognitive impairment are associated with metabolic dysfunction, oxidative stress, inflammation, and disrupted neurotrophic signaling; however, the mechanisms linking exercise-induced molecular changes to cognitive improvement remain incompletely understood. This study investigated whether a 12-week moderate-intensity aerobic exercise program modulates circulating irisin, leptin, and brain-derived neurotrophic factor (BDNF) and their associations with cognitive performance in older adults stratified by cognitive status. Sixty participants were classified into normal cognitive function (NCF), mild cognitive impairment (MCI), and moderate cognitive impairment (MoCI) groups according to Montreal Cognitive Assessment (MoCA) scores and completed supervised aerobic training for 12 weeks. Anthropometric and metabolic parameters together with oxidative stress markers (malondialdehyde, total antioxidant status, and superoxide dismutase), inflammatory cytokines (IL-6 and TNF-α), and circulating irisin, leptin, and BDNF were evaluated before and after intervention. Exercise significantly improved metabolic indices, antioxidant capacity, and inflammatory profiles across all groups (p < 0.05 to p < 0.001). Circulating irisin and BDNF increased, whereas leptin levels decreased following training. Improvements were also observed in global cognitive performance and specific domains including executive function, attention, and memory, with greater responses in participants with MCI and MoCI. Changes in irisin and BDNF showed positive associations with MoCA domains, whereas leptin demonstrated inverse relationships. These findings suggest that aerobic exercise improves cognitive function through coordinated regulation of myokine and neurotrophic signaling pathways alongside reductions in oxidative stress and inflammation, particularly in older adults with cognitive impairment. These findings also, support further controlled studies to clarify causal relationships and underlying mechanisms.