Biopsychosocial Phenotypes and Potential Mechanisms in CHARTER

项目总结

PROJECT SUMMARY People with HIV (PWH) experience a diverse set of CNS complications including cognitive and mood disorders. CNS complications may occur even in individuals taking antiretroviral therapy (ART) to suppress HIV RNA, moreover, recent studies suggest HIV infection may accelerate aging among PWH. However, accelerated aging has not been carefully examined in the context of brain structure and may be complicated by the diversity in CNS complications among PWH. Studies based on magnetic resonance imaging (MRI) show a relationship between accelerated biological aging and accelerated brain atrophy. The proposed study aims to calculate “brain age”, which is a marker of biological aging estimated from structural neuroimaging variables, including cortical thickness and subcortical volume. Estimated brain age found to be greater than an individual’s chronological age is thought to reflect an accumulation of age-related changes to the brain. To better characterize the mechanisms of central nervous system (CNS) biotypes in people with HIV (PWH), the proposed supplement aims to extract cortical thickness and subcortical volume measures derived from MRI scans to compare estimated brain age to chronological age, telomere length and mitochondrial DNA copy numbers (biological markers of aging). The project is leveraged through the parent proposal (R01MH12520- 02), which will use clustering methods to assess CNS biotypes in PWH. Supplement Specific Aim 1 is to estimate brain age in the cohort using a composite measure of cortical thickness and subcortical volume to compare it to chronological age and biomarkers of biological aging. We propose to use a Least Absolute Shrinkage and Selection Operator (LASSO) regression to derive brain age, a method that works well with limited sample sizes. We hypothesize that cortices will be thinner (consistent with older brain age) among PWH who have adverse CNS biotypes when compared to the reference group of PWH who perform as expected on assessments of cognition, mood, and daily functioning. Supplement Specific Aim 2 is to determine how brain age relates to different CNS biotypes identified by machine learning in the parent project and how brain age relates to historical HIV-Associated Neurocognitive Disorders diagnosis. We will include health-related variables as covariates in the model, since they are associated with cognitive decline and older brain age. For example, cardiovascular risk factors, high levels of alcohol intake, and stroke risk score are associated with brain aging. We also hypothesize that estimated brain age will be accelerated among PWH with adverse CNS biotypes compared to the reference group of PWH. Disentangling the cognitive and biological effects of HIV in older adults and their relation to mental health will advance the HIV field through informing our understanding of mental health conditions among people with HIV. This proposed diversity supplement will provide the applicant with critical training in neuroimaging, machine learning, telomere and mitochondrial DNA count research, which will broaden her research skillset and understanding of neurobiological mechanisms.