Combined effects of aging and HIV infection on semantic verbal fluency: A view of the cortical hypothesis through the lens of clustering and switching

Abstract

The profile of HIV-associated neurocognitive disorders (HAND) has classically been characterized as “subcortical,” but questions have arisen as to whether aging with HIV in the antiretroviral therapy era has subtly shifted the expression of HAND into a more “cortical” disorder (e.g., decay of semantic memory stores). We evaluated this hypothesis by examining semantic fluency and its component processes (i.e., clustering and switching) in 257 individuals across four groups stratified by age (<40 and ≥50 years) and HIV serostatus. Jonckheere–Terpstra tests revealed significant monotonic trends for the combined effects of HIV and aging on overall semantic (and letter) fluency and switching, but not cluster size, with greatest deficits evident in the older adults with HIV infection. Within the older HIV-infected cohort, poorer switching was uniquely associated with self-reported declines in instrumental activities of daily living and deficits in learning and executive functions, but not semantic memory. Results suggest that HIV infection and aging may confer adverse additive effects on the executive components of semantic fluency (i.e., switching), rather than a degradation of semantic memory stores (i.e., cluster size), which is a profile that is most consistent with combined frontostriatal neuropathological burden of these two conditions.

Keywords:

• Immunologic disorders
• Geropsychology
• Verbal fluency
• Executive functions
• Cognitive neuropsychology

Acknowledgments

The San Diego HIV Neurobehavioral Research Program (HNRP) group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and it includes: Director: Igor Grant; Co-Directors: J. Hampton Atkinson, Ronald J. Ellis, J. Allen McCutchan; Center Manager: Thomas D. Marcotte; Jennifer Marquie-Beck; Melanie Sherman; Neuromedical Component: Ronald J. Ellis (P.I.), J. Allen McCutchan, Scott Letendre, Edmund Capparelli, Rachel Schrier, Terry Alexander, Debra Rosario, Shannon LeBlanc; Neurobehavioral Component: Robert K. Heaton (P.I.), Steven Paul Woods, Mariana Cherner, David J. Moore, Matthew Dawson; Neuroimaging Component: Terry Jernigan (P.I.), Christine Fennema-Notestine, Sarah L. Archibald, John Hesselink, Jacopo Annese, Michael J. Taylor; Neurobiology Component: Eliezer Masliah (P.I.), Cristian Achim, Ian Everall (Consultant); Neurovirology Component: Douglas Richman (P.I.), David M. Smith; International Component: J. Allen McCutchan (P.I.); Developmental Component: Cristian Achim (P.I.), Stuart Lipton; Participant Accrual and Retention Unit: J. Hampton Atkinson (P.I.), Rodney von Jaeger; Data Management Unit: Anthony C. Gamst (P.I.), Clint Cushman (Data Systems Manager); Statistics Unit: Ian Abramson (P.I.), Florin Vaida, Reena Deutsch, Anya Umlauf, Tanya Wolfson. This research was supported by National Institutes of Health Grants P30-MH62512, P01-DA12065, and T32-DA31098. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States Government.