Divergent roles of APOAI and APOM in the identification of alcohol use disorder and their association with inflammation and cognitive decline: A pilot study

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2024

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Oxford University Press
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Escudero, B., López-Valencia, L., Arias Horcajadas, F., & Orio, L. (2024). Divergent Roles of APOAI and APOM in the Identification of Alcohol Use Disorder and Their Association With Inflammation and Cognitive Decline: A Pilot Study. The international journal of neuropsychopharmacology, 27(7), pyae029. https://doi.org/10.1093/ijnp/pyae029

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Background: Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition. Methods: A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n = 33; 72.7% men) and healthy controls (n = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated. Results: Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample. Conclusions: The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.

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Significance Statement Cognitive impairment is a common feature among alcohol use disorder (AUD)-diagnosed individuals, ranging from absent to severe cognitive deterioration. Early identification of vulnerable patients with cognitive impairment attending an alcohol detoxification program would help the clinicians to provide them with proper assistance, since the diagnostic procedures for cognitive impairment rely on resource-intensive neuropsychological evaluations, often leading to delays in patient categorization and intervention. Our pilot study investigates peripheral biomarkers associated with diagnosis and associated cognitive impairment by understanding the relationship between plasma apolipoproteins, inflammation and cognitive decline in AUD. We showed elevated APOAI and decreased APOM plasma levels associated with inflammation and cognitive deterioration in patients, helping to identify the presence/absence of the disorder and cognitive status. Our study offers a preliminary quantifiable biological approach to support neuropsychological assessment and diagnostic procedures, since we identified plasma APOAI and APOM as potential biomarkers for AUD and related cognitive decline.

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