The Effects of Appropriate Perioperative Exercise on Perioperative Neurocognitive Disorders: a Narrative Review

Abstract

Perioperative neurocognitive disorders (PNDs) are now considered the most common neurological complication in older adult patients undergoing surgical procedures. A significant increase exists in the incidence of post-operative disability and mortality in patients with PNDs. However, no specific treatment is still available for PNDs. Recent studies have shown that exercise may improve cognitive dysfunction-related disorders, including PNDs. Neuroinflammation is a key mechanism underlying exercise-induced neuroprotection in PNDs; others include the regulation of gut microbiota and mitochondrial and synaptic function. Maintaining optimal skeletal muscle mass through preoperative exercise is important to prevent the occurrence of PNDs. This review summarizes current clinical and preclinical evidence and proposes potential molecular mechanisms by which perioperative exercise improves PNDs, providing a new direction for exploring exercise-mediated neuroprotective effects on PNDs. In addition, it intends to provide new strategies for the prevention and treatment of PNDs.

Keywords: Exercise; Gut microbiota; Mitochondria; Neuroinflammation; Perioperative neurocognitive disorders; Postoperative cognitive dysfunction; Postoperative delirium.

Fig. 1

Molecular mechanisms through which exercise may affect cognitive function. Surgical procedures can activate damage-associated molecular patterns (DAMPs), further activating macrophages. Activated macrophages can secrete cytokines through the damaged BBB, further leading to microglia activation in the hippocampus. After being activated, microglia can be divided into M1 and M2 phenotypes. M1-type microglia produce pro-inflammatory cytokines to damage neurons. M2-type microglia secrete anti-inflammatory cytokines participating in tissue repair and extracellular matrix reconstruction. Surgical trauma makes microglia develop M1 polarization, leading to a vicious circle of neuroinflammation progression. Exercise can promote microglia development in M2 polarization and inhibit the level of pro-inflammatory cytokines to promote neuronal recovery. Exercise can inhibit the production of valeric acid by altering the diversity of gut microbiota. Valeric acid produced by gut microbiota inhibited neurogenesis, reduced the dendritic branches and spine density, and increased the production of pro-inflammatory cytokines in the hippocampus. At the same time, exercise can also increase skeletal muscle mass, secrete the muscle factor irisin, and release it into the peripheral blood. Irisin crosses the BBB to promote the production of BDNF and thus induce neurogenesis. Furthermore, exercise regulates mitochondrial dynamics in the hippocampus, thus ensuring mitochondrial quality and reducing mitochondrial abnormalities. Finally, exercise modulates synaptic plasticity by acting on NMDA receptors at the synapse

Fig. 2

Impact of different types of exercise on the brain. In animal studies, swimming and running have been shown to reduce pro-inflammatory cytokines and regulate gut microbiota, thereby improving post-operative cognitive function. In human studies, walking, multicomponent exercise, and resistance exercise can prevent cognitive decline. Rehabilitation exercise has a protective effect on post-operative cognitive function in elderly patients