Cognitive performance is enhanced by aerobic-strength training, and related to physical fitness and reduced platinum levels in testicular germ cell cancer survivors

Platinum-based chemotherapy can accelerate cognitive and metabolic decline in cancer survivors. Physical exercise has a potential to reduce chemotherapy-related toxicity. Our aim was to assess the effects of aerobic-strength training on cognitive functions, physical fitness and metabolism in testicular germ cell tumour (TGCT) survivors, treated with platinum-based chemotherapy. TGCT survivors were enrolled in a 6-month intervention (supervised aerobic-strength training / controls n=20 / 8, age 42.1±7.6 yrs, BMI:27.7±3.8 kg/m², VO2max:29.2±6.7 mlO2/kg/min, 1-20 years post-treatment). Abdominal adiposity (MRI), cardiorespiratory fitness (VO2max, spiroergometry), muscle strength (dynamometry), energy metabolism (indirect calorimetry), cognitive functions (FACT-Cog, Memtrax, CogState, Auditory Verbal Learning Test/AVLT), serum glycemia, insulinemia, lipid profile, plasma adiponectin (ELISA), platinum and zinc (Mass Spectrometry) were assessed before and after intervention. Exercise training improved delayed and short-term memory recall (AVLT), reduced visceral adiposity (MRI, p<0.01), increased circulating HDL-cholesterol (p<0.01), cardiorespiratory fitness (VO2max) and muscle strength (p=0.01) compared to non-active controls. Training-induced changes in delayed memory recall positively correlated with improvements in VO2max, supporting a link between cognition and cardiorespiratory fitness. Training intervention normalized residual plasma platinum and increased zinc levels (both p<0.01). Platinum levels (p<0.001) and number of chemotherapy cycles (p=0.06) were the best predictors of memory function. Aerobic-strength training may improve memory in parallel with increasing physical fitness and reducing circulating platinum levels in TGCT survivors. Exercise represents an effective tool in the long-term management of cancer survivors, with a potential to reduce residual chemotherapy burden and increase physical fitness, which are linked to enhanced cognitive performance. Funding:APVV19-0411,VEGA2/0161/24,VEGA 2/0144/23,FWF KLI1122