Neuroscientists at Georgetown University Medical Center have found in a small study that although a group of HIV+ older individuals scored “cognitively normal” in standard neuropsychology testing, a scan of their brains tells a different story.
Published Nov. 17 in the journal AIDS Care, functional MRI (fMRI) scans, taken while participants were performing an alternating face-gender/word-semantic task, revealed that HIV+ individuals in the study showed deficits in cognitive functioning, compared to an age matched healthy controls.
Despite advances in treatment, HIV-associated neurocognitive disorder, or HAND, remains one of most common disorders in individuals with HIV infection. Previous studies have suggested about 30 to 60 percent of individuals with HIV-infection are affected, says neuroscientist Xiong Jiang, PhD, the lead author of the new study. This study suggests that cognitive impairments in HIV-infected 50 years or older individuals might be even more prevalent than previously proposed.
“This could be due to the fact that some standard neuropsychology tests might be insensitive to HAND”, says Jiang. The new study used an experimental design that has been validated to study cognitive control (the ability to guide thought and action in accordance with current goals in a given environment) in healthy younger adults.
During the scanning, the participants were cued (unpredictably) to judge the gender of the face (male versus female) or the meaning of the word (e.g., animate for “tiger” and inanimate for “table”) on superimposed face-word images. A switch (after the cue) in task often leads to an increase in reaction time and a decrease in accuracy (known as switching cost).
The HIV+ group was significantly slower in adjusting to change in tasks, which correlates with brain dysfunctions in the dorsal anterior cingulate cortex (dACC), one of the key executive regions. This collar-shaped area is near the front of the brain, and damage to this region has been linked to many cognitive impairments, including executive deficits and apathy.
“Intriguingly, both impairments are highly prevalent in individuals with HIV-infection, suggesting dACC might be one of commonly affected brain regions in HIV and a potential neural target for therapies,” says Jiang.
“These findings, although preliminary, could have a significant implication for public health,” says Jiang, “While there is no proven treatment that can effectively treat HAND other than control HIV replication, it is important for caregivers, families and the individuals themselves to know if they are affected.”
Jiang says he will now study HAND in a larger population — research supported by a $2 million grant from the National Institute of Mental Health (1R01MH108466-01) to further develop his fMRI-based biomarkers with the potential to guide and evaluate early and targeted therapies.
Co-authors include Maximilian Riesenhuber from Georgetown University, and Rebecca Barasky, Halli Olsen and Manya Magnus from George Washington University.
Funding: This cross-institutional and cross-disciplinary project is supported by the National Center for Research Resources (UL1RR031988) and the District of Columbia Developmental Center for AIDS Research (P30AI087714).
Source: Karen Teber – Georgetown University Medical Center
Image Credit: The image is credited to Xiong Jiang, Georgetown University Medical Center
Original Research: Abstract for “Behavioral and neuroimaging evidence for impaired executive function in “cognitively normal” older HIV-infected adults” by Xiong Jiang, Rebecca Barasky, Halli Olsen, Maximilian Riesenhuber and Manya Magnus in AIDS Care. Published online November 17 2015 doi:10.1080/09540121.2015.1112347
Behavioral and neuroimaging evidence for impaired executive function in “cognitively normal” older HIV-infected adults
The increased prevalence of HIV among adults >50 years underscores the importance of improving our understanding of mechanisms causing HIV-associated neurocognitive disorders (HAND). Identifying novel and noninvasive diagnostic predictors of HAND prior to clinical manifestation is critical to ultimately identifying means of preventing progression to symptomatic HAND. Here, using a task-switching paradigm, in which subjects were cued (unpredictably) to perform a face-gender or a word-semantic task on superimposed face and word images, we examined the behavioral and neural profile of impaired cognitive control in older HIV + adults (N = 14, 9 HIV+). Functional magnetic resonance imaging (fMRI) and behavioral data were acquired while subjects were performing the face-gender or word-semantic task. We found that, despite comparable performance in standard neuropsychology tests that are designed to probe executive deficits, HIV-infected participants were significantly slower than uninfected controls in adapting to change in task demand, and the behavioral impairments can be quantitatively related to difference in fMRI signal at the dorsal anterior cingulate cortex (ACC). Due to the limited sample size of this hypothesis-generating study, we should take caution with these findings and future studies with a large and better matched sample size are needed. However, these rather novel findings in this study have a few important implications: first, the prevalence of cognitive impairments in HIV+ older adults might be even higher than previously proposed; second, ACC (in particularly its dorsal region) might be one of the key regions underlying cognitive impairments (in particularly executive functions) in HIV; and third, it might be beneficial to adopt paradigms developed and validated in cognitive neuroscience to study HAND, as these techniques might be more sensitive to some aspects of HIV-associated neurocognitive impairments than standard neuropsychology tests.
“Behavioral and neuroimaging evidence for impaired executive function in “cognitively normal” older HIV-infected adults” by Xiong Jiang, Rebecca Barasky, Halli Olsen, Maximilian Riesenhuber and Manya Magnus in AIDS Care. Published online November 17 2015 doi:10.1080/09540121.2015.1112347