ORCID ID

0000-0001-9107-4993

Graduation Date

Spring 5-8-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Neuroscience

First Advisor

Tony W. Wilson

Abstract

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed participants with HIV infection and 133 uninfected controls age 22-72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of participants to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age, and then used individual estimations of epigenetic age to understand the relationship between age advancement and brain structure. Finally, we studied the effects of HIV-associated neurocognitive disorder.

In brain structure, HIV-infection was related to grey matter reductions, independent of age. Using epigenetic age as a biomarker for age advancement, individual HIV-related age advancement was associated with reductions in total grey matter. HIV-associated neurocognitive disorder was associated with decreases in thalamic and hippocampal grey matter. Examining functional resting state networks, HIV-infection and age were independently associated with broad increases in between-network connectivity. In contrast to the structural results however, changes in resting state functional connectivity were not significantly associated with epigenetic age advancement. With respect to HAND, increases in functional connectivity with the ventral attention network appeared to be driven by PWH with HAND. Finally, in resting state oscillatory activity, while independent age related changes were identified in delta power, beta power, and alpha peak frequency, no effects of HIV were identified. Exploring these null results, post-hoc Bayesian analyses showed evidence that many oscillatory metrics were equivalent between PWH and uninfected controls. In conclusion, despite viral suppression, accentuated grey matter loss and resting state functional network reorganization is evident with HIV-infection, while resting oscillatory activity is largely preserved. Greater biological age advancement appears to specifically relate to grey matter loss. These findings are a critical step towards understanding and treating the aging brain of PWH.

Available for download on Wednesday, March 08, 2023

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