Klotho and neurotrophic factors (NGF, BDNF, GDNF) in alcohol use disorder: Clinical and cognitive associations

AIM: Alcohol use disorder (AUD) is a chronic brain disease that disrupts neuroplasticity and cognition. We examined whether serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line–derived neurotrophic factor (GDNF), and Klotho are associated with cognitive performance, psychiatric symptoms, and clinical variables in AUD. MATERIALS AND METHODS: This cross-sectional study included 40 male AUD patients and 40 healthy controls recruited from the Sakarya University Training and Research Hospital. Participants completed a sociodemographic form and the Hamilton Anxiety (HAM-A), Hamilton Depression (HDRS), and Montreal Cognitive Assessment (MOCA). The Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-AR) and the Michigan Alcoholism Screening Test (MAST) were administered only to patients. Serum BDNF, GDNF, NGF, and Klotho were measured by ELISA. Data were analyzed in SPSS 28 RESULTS: Cognitive performance (MoCA total) was lower in AUD than controls (p<0,001). NGF was higher in controls (p<0,001), whereas between-group differences for BDNF and GDNF were not significant (p=0,062 and p=0,102, respectively). Klotho showed a trend toward higher levels in controls but did not reach significance (p=0,051). In patients, Klotho and NGF correlated positively (rs=0,752; p=0,001). MOCA correlated negatively with cumulative and monthly alcohol load (e.g., cumulative r=-0,582; p<0,001). In multiple regression, monthly alcohol load (β=-0,500; p<0,001), income (β=0,357; p=0,004), and education (β=0,234; p=0,045) predicted MoCA; NGF and Klotho were not significant predictors. CONCLUSION: In AUD, cognitive impairment relates strongly to alcohol load, and lower NGF may be linked to worse cognition. Although the group difference in Klotho was not significant, its strong correlation with NGF suggests biological relatedness. Neurotrophic factors and Klotho warrant further investigation as candidate biomarkers for the neurobiology of AUD and cognition. Keywords: AUD, BDNF, GDNF, klotho, NGF