Oxidative stress and antioxidant defenses in mild cognitive impairment: A systematic review and meta-analysis

This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)= 0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NSassociated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95% CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.

Automated summary

This study systematically reviewed and meta-analyzed the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of individuals with mild cognitive impairment (MCI). The results showed that MCI individuals have higher O&NS/ANTIOX ratio, increased lipid peroxidation and O&NS-associated toxicity, and reduced glutathione defenses compared to healthy controls. MCI is also associated with increased homocysteine and decreased non-vitamin and vitamin antioxidant defenses. The findings suggest that MCI is partly attributed to neuro-oxidative toxicity and highlight the potential of lipid peroxidation and the glutathione system as targets for MCI treatment or prevention.