Malondialdehyde in cognitive impairment: A systematic review and meta-analysis

Malondialdehyde (MDA) is a marker of lipid peroxidation and oxidative stress, processes involved in neurodegeneration and cognitive decline. This systematic review and meta-analysis evaluated circulating MDA concentrations in individuals with Alzheimer's disease (AD) or mild cognitive impairment (MCI) compared to cognitively healthy controls. A systematic search of PubMed, Scopus, and Web of Science up to 18 July 2025 identified 36 studies (48 group comparators) including 2132 patients and 2169 controls. Pooled analysis revealed significantly higher MDA concentrations in cognitively impaired individuals (SMD = 1.46, 95 % CI 1.10-1.83; p < 0.001), with consistent increases in both AD (SMD = 0.82) and MCI (SMD = 1.24). Subgroup analyses showed comparable results across serum and plasma samples and across different geographical regions, while the analytical method influenced the effect size. Trim-and-fill analysis confirmed the robustness of findings despite publication bias. Circulating MDA is elevated in cognitive impairment, supporting its potential as a biomarker of early neurodegeneration and oxidative stress. Future studies should standardize measurement approaches and assess the utility of MDA for prognosis and treatment response.