AbstractBackgroundExercise improves physical fitness, cognitive functions & metabolism in the elderly. Evidence from animal models suggests the role for mediators from muscle or adipose tissue in the exercise‐induced brain plasticity (1). Knowledge on the regulation of these potentially neuroprotective molecules by exercise in humans is limited (2,3). We investigated effects of 3‐month supervised aerobic‐strength training on serum & cerebrospinal fluid/CSF adiponectin in the elderly, in association with cognitive functions & brain volumetry.MethodThe population consisted of sedentary elderly (n = 38, 10M/28F; 66.1±5.9yrs; BMI 26.3±3.7kg/m2). Body composition (MRI), physical fitness (Rockport test), muscle strength (dynamometry), motor tests (walking speed & chair stand tests), resting energy expenditure & substrate preference (REE, RQ, indirect calorimetry), insulin sensitivity & metabolic flexibility (euglycemic hyperinsulinemic clamp/EHC), cognitive functions (cognitive tests), brain volumetry (MRI), serum glucose & insulin were assessed.ResultTraining reduced BMI, blood pressure and insulinemia, while improving insulin sensitivity & metabolic flexibility (EHC), maximal aerobic capacity (VO2max), motor performance, and memory (ACE‐R). Improvements in cognitive functions were more pronounced in patients with MCI (p<0.05). Training led to a small but consistent increase of CSF adiponectin in cognitively healthy seniors (p<0.05), while no change was observed in MCI (p>0.1). CSF adiponectin was positively associated with psychomotor attention score (CogState), and it strongly correlated with the volume of corpus callosum normalized to intracranial volume. Training did not regulate serum adiponectin.ConclusionRelatively short‐term aerobic‐strength training can improve cognitive functions together with a spectrum of anthropometric, metabolic and fitness parameters, which may slow down the ageing‐related cognitive decline. Exercise modulated levels of adiponectin in CSF which correlated with cognitive functions and volume of specific brain areas. This might indirectly indicate the role for adiponectin in the exercise‐related brain plasticity in the elderly. Funding: APVV 20‐0466, VEGA‐2/0076/22, COST DePASS, APVV 15‐0253