Background: Type 2 diabetes (T2DM) affects brain structure and function, and is associated with an increased risk of dementia and mild cognitive impairment. It is known that exercise training has a beneficial effect on cognition and the brain, at least in healthy people, but the impact of exercise training on cognition and the brain remains to be fully elucidated in patients with T2DM. Methods: This paper systematically reviews studies that evaluate the effect of exercise training on cognition in T2DM, and aims to indicate the most beneficial exercise modality for improving or preserving cognition in this patient group. In addition, the possible physiological mediators and targets involved in these improvements are narratively described in the second part of this review. Papers published up until October 2023 were searched by means of the electronic database PubMed. Studies directly investigating the effect of any kind of exercise training on the brain or cognition in patients with T2DM, or animal models thereof, were included, with the exception of human studies assessing cognition only at one time point, and studies combining exercise training with other interventions (e.g. dietary changes, cognitive training, etc.). Results: For the systematic part of the review, 24 papers were found to be eligible. 20 out of 24 papers (83.3%) showed a significant positive effect of exercise training on cognition in T2DM, of which four studies only showed a moderate significant effect. Four papers (16.7%) did not show a significant effect of exercise on cognition in T2DM, but two of them did show a positive trend. Similar effects were found for resistance and endurance exercise, with both possibly requiring a minimal intensity to reach cognitive improvement. In addition, BDNF, lactate, leptin, adiponectin, GSK3β, GLP-1, the AMPK/SIRT1 pathway, and the PI3K/Akt pathway were identified as plausible mediators directly from studies investigating the effect of exercise training on the brain in T2DM. Conclusion: Overall, exercise training beneficially affects cognition and the brain in T2DM, with resistance and endurance exercise having similar effects. However, additional studies comparing the effect of different exercise intensities are needed to determine the optimal exercise intensity for cognitive improvement. Furthermore, we were able to define several mediators involved in the effect of exercise training on cognition in T2DM, but further research is necessary to unravel the entire process.
