UC San Diego

Deficit models that predominate neuroHIV research describe adverse, synergistic effects of HIV and older age on neurocognitive impairment, yet many older persons with HIV (PWH) exhibit unimpaired neurocognition. HIV-seronegative studies have identified a subgroup of elders with youthful neurocognition, termed SuperAgers (SA). SA demonstrate stable neurocognitive trajectories and robust neurobiological integrity, consistent with models of cognitive and physiological reserve (CR and PR). However, the construct validity of SuperAging in HIV, including its prevalence, trajectory, and biopsychosocial correlates, is unknown. This three-paper dissertation: 1) established classification criteria for SuperAging in PWH; 2) examined the joint influence of CR and PR on SuperAging; and 3) characterized longitudinal trajectories of SuperAging. All three studies used archival data from older PWH (age range: 50-69) enrolled in studies coordinated by the HIV Neurobehavioral Research Program. Study 1 (N=724, Saloner et al., 2018). Individuals with intact global neurocognition based on normative standards for healthy 25 year-olds were classified as SA (n=124 [17.1%]). SA had similar HIV disease severity but better real-world outcomes (e.g., functional independence) than cognitively normal but non-super (CN) and cognitively impaired (CI) individuals. Study 2 (N=394, Saloner et al., 2022). CR was operationalized as estimated premorbid verbal intelligence (i.e., WRAT4 Reading subtest) and PR was operationalized with a validated disease burden index composed of 39 health variables. Higher PR predicted linear increases in odds of SA (vs. CN and CI) and higher CR predicted a quadratic ‘J-shaped’ change in odds of SA compared to CN (i.e., odds of SA>CN only above 35th percentile of CR). Study 3 (N=184, Saloner et al., 2021). Growth mixture modeling identified a 3-class solution that included Class 1Stable Elite (n=31 [16.8%], a latent class defined by stable and elite global neurocognition across a 5-year longitudinal period. Higher CR, PR, and SA status at baseline increased odds of Class 1Stable Elite membership. Findings support SuperAging in HIV as a construct reflecting neurocognitive resilience that converges with markers of robust biopsychosocial health. Replication of methodology in even older PWH (i.e., 70+ years) may improve characterization of cognitive risk and resilience, particularly among PWH without overt neurocognitive impairment.