A single low dose of hydrocortisone enhances cognitive functioning in HIV-infected women

Abstract

Objective: Low-dose hydrocortisone (LDH) enhances aspects of learning and memory in select populations including patients with posttraumatic stress disorder and HIV-infected men. HIV-infected women show impairments in learning and memory, but the cognitive effects of LDH in HIV-infected women are unknown.

Design: Double-blind, placebo-controlled, cross-over study examining the time-dependent effects of a single low-dose administration of hydrocortisone (10 mg oral) on cognition in 36 HIV-infected women. Participants were first randomized to LDH or placebo and then received the opposite treatment one month later.

Methods: Cognitive performance was assessed 30 min and 4 h after pill administration to assess, respectively, nongenomic and genomic effects. Self-reported stress/anxiety and salivary cortisol were assessed throughout sessions.

Results: LDH significantly increased salivary cortisol levels versus placebo; levels returned to baseline 4-h postadministration. At the 30-min assessment, LDH enhanced verbal learning and delayed memory, working memory, behavioral inhibition, and visuospatial abilities. At the 4-h assessment, LDH enhanced verbal learning and delayed memory compared with placebo. LDH-induced cognitive benefits related to reductions in cytokines and to a lesser extent to increases in cortisol.

Conclusion: The extended benefits from 30 min to 4 h of a single administration of LDH on learning and delayed memory suggest that targeting the hypothalamic-pituitary-adrenal axis may have potential clinical utility in HIV-infected women. These findings contrast with our findings in HIV-infected men who showed improved learning only at the 30-min assessment. Larger, longer term studies are underway to verify possible cognitive enhancing effects of LDH and the clinical significance of these effects in HIV.

Figure 1.

Cohen’s d effect size for the time-dependent effects of low dose hydrocortisone versus placebo on cognition in HIV-infected women. Note. **p<0.01; *p<0.05. ^T=0.06. WM=working memory.

Figure 2.

The magnitude of increase in salivary cortisol responsivity due to low dose hydrocortisone (LDH) is associated with verbal memory improvement (LHD – placebo) at the delayed, slow 4-hour time point but not at the immediate, rapid 30 minute time point. Note. HVLT=Hopkins Verbal Learning Test.

Figure 3.

Raw correlations between immune responsivity and cognitive improvement due to low dose hydrocortisone (LDH) at the (A) immediate, rapid (30 min) and (B) delayed, slow (4 hour) time point. Note. ***p<0.01; **p<0.05; *p<0.10. Immune responsivity calculated as placebo minus LDH; Cognitive improvement was calculated as LDH minus placebo. Thus, when the magnitude of the association is positive (blue) that means that the greater the reduction in inflammatory markers is associated with greater cognitive improvement with LDH. All women (n=36) had values for IL-8, IL-6, IL-1β, and TNF-α. 35 women had values for IP-10, MCP1, CRP, and MIG. 32 women had values for MMP9. 23 women had values for sCD163. 19 women had values for TNFRII. 18 women had values for MIF and MMP2. 17 women had values for sCD14. IL-8, IL-6, IL-1β, TNF-α, IP-10, MCP1, CRP, MIG, and MMP9 were part of the original panel of markers; thus missing values on these immune markers reflects sample availability. sCD163, sCD14, TNFRII, MIF, and MMP2 were added as the study progressed and thus not all women have these markers.