HIV-associated neurocognitive disorders (HAND) are common among adults infected with HIV, causing a variety of possible symptoms including deficits in memory and cognition; behavioral changes; motor difficulties; and in severe cases, dementia. In adults, HAND has been shown independently to worsen medication adherence and predict non-central nervous system morbidity and overall HIV mortality.
Around half of HIV-infected adults show some level of neurocognitive impairment; however, to date there has been little study of how HIV impacts the unique chemical environment of the developing adolescent brain. To bridge that adult-pediatric divide, CHOP neurologist Jennifer McGuire, MD, MSCE, is conducting a pilot study to understand the neurocognitive effects of HIV in adolescents and young adults with acquired infection.
“The adolescent brain is still actively developing into a person’s mid- to late-20s, refining all of its pathways and connections” says McGuire. “We suspect that when HIV infects an adolescent or young adult, it not only instigates the neuropathogenesis we see in adults, but may also disrupt normal brain maturation that typically goes on during this period. This disruption would result in unique patterns of cognitive impairment in youth compared to adults, which may have specific clinical implications in their lives as they grow to become adults.”
These differences are important to understand because a quarter of the 50,000 new infections in the United States annually are among youth 13 to 24 years old. With systemic HIV therapy having become so effective, these youth stand to live a long time with chronic neurologic deficits.
While the brain reaches its maximum physical size in the early teenage years, the microstructure continues to prune and myelinate into young adulthood, reinforcing learning, memory, and complex processing. Areas that control logic, abstract thought, and planning (prefrontal cortex) also are late to mature.
McGuire’s study will gather 3 separate data sets for each adolescent: a neurocognitive and psychiatric assessment, plasma biomarkers, and MRI imaging of the brain. For the first, McGuire will identify cognitive, psychiatric, and functional impairments by testing factors such as speed of processing, executive function, motor skills, attention shifting, verbal memory, and mood. She will then correlate these findings with inflammatory and neurodegenerative biomarkers from the blood as well as MRI measurements of brain volume and structures. Her goal is not only to understand HAND in adolescents, but also to uncover biomarkers that can identify and characterize the disease.
McGuire suspects that this HAND phenotype, as well as its severity, will prove unique to the adolescent and young adult population. Her findings also could have major implications on the lives of a population that is in school and entering the work force. A better understanding of how HIV is affecting their brains could help improve educational plans and guide young adults to jobs better suited to them.
“If there really is a unique neuropathophysiology of HIV in these youth compared to adults, that might also warrant specific targeted therapies in the future,” adds McGuire. “But before we can even think about tailoring therapies, we first have to understand what is happening on a neurobiological basis.”