Bagenda, Charles NkubiMudondo, HopeSsemwanga, ElastusNzaramba, DanielSsedyabane, FrankOjuko, SamuelMusinguzi, BensonAkiteng, WinnieAgaba, Bosco BekiitaOsuwat, Lawrence ObadoMaling, SamuelRugera, Simon PeterTusubira, Deusdedit2025-09-152025-09-152025-08-11Bagenda CN, Mudondo H, Ssemwanga E, et al. (2025). Association of high serum aspartate transaminase to high density lipoprotein-cholesterol ratio with probable dementia among people living with HIV on antiretroviral therapy in Southwestern Uganda. SAGE Open Medicine, 13. doi:10.1177/205031212513743912050-3121https://dir.muni.ac.ug/handle/20.500.12260/772Objectives: Previous studies present conflicting evidence on the relationship between hepatocellular damage biomarkers and dementia risk. While elevated serum transaminases have been associated with mild cognitive impairment, other studies link lower transaminase levels and reduced high-density lipoprotein-cholesterol levels to increased risk of cognitive decline. This study investigated the association between serum transaminase-to-high-density lipoprotein-cholesterol ratios and probable dementia among people living with HIV on antiretroviral therapy. Methods: We conducted a secondary data analysis using a dataset from a cross-sectional study conducted among 377 people living with HIV on dolutegravir-based antiretroviral therapy in southwestern Uganda. Probable dementia was screened using the brief Community Screening Instrument for Dementia and defined as a Community Screening Instrument for Dementia cognitive score ⩽4. Serum alanine aminotransferase/high-density lipoprotein-cholesterol and aspartate aminotransferase/high-density lipoprotein-cholesterol ratios were calculated from the respective serum transaminases and high-density lipoprotein-cholesterol divided into tertiles. We used logistic regression to assess the association between the independent variables and probable dementia. Results: The median age of the study participants was 44 years (interquartile range: 30–59), with 56.2% being female. The median total cholesterol/high-density lipoprotein-cholesterol levels were significantly higher in participants with probable dementia compared to those without (3.86 versus 3.22, p = 0.03). Aspartate aminotransferase/high-density lipoprotein-cholesterol and alanine aminotransferase/high-density lipoprotein-cholesterol levels were also higher among participants with probable dementia compared to those without, although the differences did not reach statistical significance. In the fully adjusted model, compared to participants in the first tertile of aspartate aminotransferase/high-density lipoprotein-cholesterol ratio, the odds of probable dementia were higher in the second tertile (adjusted odds ratio: 1.71; 95% confidence interval: 0.62–4.74; p = 0.301) and significantly elevated in the third tertile (adjusted odds ratio: 4.48; 95% confidence interval: 1.15–17.46; p = 0.031). Conclusions: The findings suggest that an elevated aspartate aminotransferase/high-density lipoprotein-cholesterol ratio is significantly associated with probable dementia among people living with HIV on dolutegravir-based antiretroviral therapy. A high aspartate aminotransferase/high-density lipoprotein-cholesterol ratio is potentially associated with cognitive decline in this population.enAST/HDL-C ratioDementiaArticle