Physical exercise improves memory in sedentary middle-aged adults: Are these exercise-induced benefits associated with S-Klotho and 1,25-dihydroxivitamin D? The FIT-AGEING randomized controlled trial.

We aimed to investigate the effect of three types of exercise interventions on memory (i.e., immediate memory (IM), long-term memory (LTM), and recognition). We also investigated whether exercise-induced changes in circulating S-Klotho and 1,25-dihydroxivitamin D (1,25(OH) D) levels were related to those observed in memory in healthy middle-aged sedentary adults. A 12-week randomized controlled trial was performed with a parallel-group design. Seventy-four participants (45-65 years old: 53% women) were randomly assigned to (1) no exercise (control) group, (2) concurrent training based on the international physical activity recommendations (PAR) group, (3) high-intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT-EMS) group. Memory outcomes were assessed using the Wechsler Memory Scale-third edition. S-Klotho plasma levels were determined according to a solid-phase sandwich enzyme-linked immunosorbent assay kit while 1,25(OH) D plasma levels were measured using a DiaSorin-Liaison immunochemiluminometric analyzer. IM-Verbal Paired Associates (IM-VPA) and IM-Logical Memory (IM-LM) were improved in both the HIIT and HIIT-EMS groups compared with the control group (all p ≤ 0.045). Exercise-induced changes in S-Klotho plasma levels were positively associated with those observed in IM, LTM, and recognition (all p ≤ 0.007), whereas exercise-induced changes in 1,25(OH) D plasma levels were directly related to changes in IM and LTM (all p ≤ 0.048). In conclusion, a 12-week HIIT intervention with or without WB-EMS seems to be the most effective exercise program to improve IM. The significant and positive associations between exercise-induced changes in S-Klotho and 1,25(OH) D levels with those observed in memory outcomes suggest that these factors may be potentially related to exercise-induced improvements of memory in middle-aged adults.