SuperAging in HIV-infected Adults: Biopsychosocial Predictors of Neurocognitive Aging Trajectories

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PROJECT SUMMARY/ABSTRACT The life expectancy of people living with HIV (PLWH) receiving antiretroviral therapy (ART) has steadily increased, with an estimated 50% of PLWH in the U.S. aged 50 years and older. Despite increased longevity in the ART-era, older PLWH are at enhanced risk for premature and accelerated development of geriatric syndromes, including neurocognitive impairment (NCI), frailty, and daily functioning dependence. NeuroHIV research preferentially studies adverse outcomes stemming from the combined neurobiological burdens of HIV and aging; however, one to two-thirds of older PLWH do not meet criteria for NCI. Despite the neurocognitive heterogeneity among neurocognitively `unimpaired' older PLWH, inter-individual differences in neurocognitive aging trajectories are poorly understood. We have recently characterized a subgroup of older PLWH with youthful neurocognition akin to that of a healthy 25 year-old, an age at which most neurocognitive capacities peak. These neurocognitively elite individuals, termed SuperAgers (SA), display comparable profiles of HIV disease severity as compared to their cognitively normal non-super and cognitively impaired counterparts, yet have better daily functioning, mental and physical health-related quality of life, fewer comorbidities, and higher premorbid IQ. These findings align with a model of cognitive and physiological reserve, suggesting that robust maintenance of cognitive and physiological resources enables SA to effectively combat the neural and physical stressors of aging with HIV. Nevertheless, these cross-sectional data do not address whether SA maintain maximal neurocognition over time, and whether such neurocognitive resilience converges with holistic indicators of biopsychosocial reserve. Assessing the validity of SA as a construct reflecting resilience against neurocognitive decline is critical toward identifying neuroprotective factors among the vulnerable population of older PLWH. Accordingly, the proposed F31 project aims to 1) characterize neurocognitive aging trajectories and determine their relation to SA in older PLWH; 2) determine biopsychosocial predictors of neurocognitive trajectories; and 3) examine potential effects of demographic, neuropsychiatric, substance use, and daily functioning factors on neurocognitive trajectories. The proposed research will employ latent growth mixture modeling using longitudinal, archival data of older PLWH from the CNS HIV Antiretroviral Therapy Effects Research program. The opportunities afforded via this F31 mechanism will facilitate the applicant's professional development toward becoming an independent academic neuropsychologist dedicated to promoting neurocognitive resilience among older PLWH.