Longitudinal Cognitive Evolution in Alcohol Use Disorder Patients: Role of Inflammation, Time of Abstinence and Apolipoprotein Profile

Alcohol use disorder (AUD) is linked to cognitive deficits that can persist even after prolonged abstinence. Research highlighted associations between plasma apolipoproteins and cognition in AUD. This study examines the longitudinal evolution of plasma apolipoproteins and inflammation in AUD patients during early and prolonged abstinence and their association with cognitive recovery. Thirty-three AUD patients from an outpatient hospital alcoholism programme were evaluated at baseline (t = 0), 6 months (t = 1) and 12 months (t = 2), along with 34 healthy controls. Cognitive performance was assessed using the TEDCA test, which measures general cognitive function (GCF). Biological assessments included plasma pro-inflammatory biomarkers (LPS and LBP) and several apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ and APOM). AUD patients showed elevated plasma LPS, APOAI, APOE, APOJ and downregulated APOM, which all normalized at t = 1, whereas cognitive improvement was significant at t = 2 compared to controls. Mixed-effects models including all covariates and within-between person decomposition, followed by correlation matrix and reduced mixed models sensitivity analysis support robust associations between better GCF and (1) the duration of abstinence and (2) within-person reductions in LPS, although apolipoprotein changes should be considered exploratory at this level. Prolonged abstinence in AUD patients normalizes plasma peripheral inflammation and apolipoprotein levels and improves cognition. Although APOAI and APOM showed opposite trajectories, as opposite biomarkers in AUD diagnosis reported previously, only the duration of abstinence and normalization of within-person blood LPS levels over time emerged as predictors of cognitive recovery.