Epigenetic Age Acceleration, Neurocognition and Oral Health in Nigerian Adolescents With and Without HIV

BACKGROUND: People living with HIV on antiretroviral therapy (ART) experience neurocognitive impairments, oral disease and epigenetic age acceleration (EAA) at higher rates than the general population. The objective of this study was to examine the associations between EAA and measures of neurocognition and oral health among adolescents living with HIV (ALHIV) and matched controls. METHODS: The Uncovering the Biological Link Between Oral and Mental Health in Adolescents Living With HIV study enrolled 116 adolescents (10-13 years old) at the University of Benin Teaching Hospital in Nigeria. Fifty-eight ALHIV and 58 age- and sex-matched HIV-unexposed-uninfected participants were included in this cross sectional analysis. Participants completed two neurocognitive tests, NeuroScreen and NIH Toolbox Cognition Battery, and clinical oral exams. Peripheral blood DNA underwent methylation profiling, and epigenetic age and EAA were calculated with six validated algorithms (Horvath1, Horvath2, Hannum, PhenoAge, GrimAge and PedBE). RESULTS: In adjusted models among all participants and ALHIV, EAA was associated with poorer verbal learning/encoding scores. Among ALHIV, EAA (GrimAge) was inversely associated with processing speed [number speed; ß, -2.58 (95% confidence interval: -4.22 to -0.94)]. Inverse and positive associations between EAA and neurocognition assessed by the NIH Toolbox were detected. Higher EAA was not significantly associated with poorer oral health in this population. CONCLUSIONS: EAA may be linked to diminished processing speed and verbal learning in ALHIV on antiretroviral therapy. Oral disease was not strongly linked to EAA in this study. These findings indicate the need for longitudinal studies of EAA and neurocognitive and oral health outcomes in this population.