Plasma myeloperoxidase predicts cognitive decline in mild cognitive impairment: a multicenter longitudinal cohort study.

Abstract

Mild cognitive impairment (MCI) is a key stage for early intervention in dementia, and its inflammatory mechanisms remain unclear. Myeloperoxidase (MPO), a key enzyme involved in inflammation and immune regulation, has not been fully studied in MCI. This multicenter longitudinal cohort study prospectively followed 133 patients with MCI for 12 months. Plasma MPO, Alzheimer's disease (AD)-related biomarkers (p-Tau181, p-Tau217, glial fibrillary acidic protein , neurofilament light chain, and Aβ42/40), inflammatory cytokines (IL-1β, IL-6, and TNF-α), neuropsychological performance, and APOE genotype were assessed at baseline and follow-up. During follow-up, 58 patients showed cognitive deterioration and 75 remained non-deteriorated. At both baseline and the 12-month follow-up, the cognitive deterioration group showed higher MPO, IL-1β, and IL-6 levels than the non-deterioration group. Within-group longitudinal changes from baseline to follow-up were modest and were not statistically significant. Cross-sectional analyses showed that MPO was associated with IL-1β, IL-6, Aβ42/40, Mini-Mental State Examination (MMSE), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) at different assessment time points. Longitudinal delta analyses showed that changes in MPO were significantly correlated with changes in MMSE, IL-1β, and IL-6, but not with changes in ADAS-Cog or Aβ42/40. After adjustment for potential confounders, MPO remained an independent predictor of cognitive deterioration in MCI (OR = 1.018, 95% CI, 1.00-1.03, p = .015). Nomogram analysis showed that MPO was the most prominent predictor in the model. These findings suggest that elevated plasma MPO may serve as a clinically accessible prognostic biomarker for risk stratification in patients with MCI.