Behavioral and neuroimaging evidence for impaired executive function in “cognitively normal” older HIV-infected adults

ABSTRACT

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.

KEYWORDS:

• Cognitive control
• HIV-associated neurocognitive disorders
• FMRI
• anterior cingulate cortex
• HAND

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Funding

This project was supported by Award Number UL1RR031988 from the National Center for Research Resources and the District of Columbia Developmental Center for AIDS Research Award Number P30AI087714. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Travel to CROI was generously supported by the District of Columbia Developmental Center for AIDS Research Award Number P30AI087714. We also appreciate the support of the Intellectual and Development Disorders Research Center (IDDRC) grant [5P30HD040677-13].