Epigenetic aging is associated with aberrant neural oscillatory dynamics serving visuospatial processing in people with HIV

Background: Despite effective antiretroviral therapy, cognitive impairment and other aging-related comorbidities are more prevalent in people with HIV (PWH) than in the general population. Previous research examining DNA methylation has shown PWH exhibit accelerated biological aging. However, it is unclear how accelerated biological aging may affect neural oscillatory activity in virally suppressed PWH, and more broadly how such aberrant neural activity may impact neuropsychological performance. Methods: In the present study, participants (n = 134) between the ages of 23 – 72 years underwent a neuropsychological assessment, a blood draw to determine biological age via DNA methylation, and a visuospatial processing task during magnetoencephalography (MEG). Our analyses focused on the relationship between biological age and oscillatory theta (4-8 Hz) and alpha (10 - 16 Hz) activity among PWH (n=65) and seronegative controls (n = 69). Results: PWH had significantly elevated biological age when controlling for chronological age relative to controls. Biological age was differentially associated with theta oscillations in the left posterior cingulate cortex (PCC) and with alpha oscillations in the right medial prefrontal cortex (mPFC) among PWH and seronegative controls. Stronger alpha oscillations in the mPFC were associated with lower CD4 nadir and lower current CD4 counts, suggesting such responses were compensatory. Participants who were on combination antiretroviral therapy for longer had weaker theta oscillations in the PCC. Conclusions: These findings support the concept of interactions between biological aging and HIV status on the neural oscillatory dynamics serving visuospatial processing. Future work should elucidate the long-term trajectory and impact of accelerated aging on neural oscillatory dynamics in PWH.