| Publication Abstract Display | | Type: Poster | | Title: CNS iron status is associated with neurocognitive function over time in HIV+ adults. | | Authors: Kaur H, Bush W, Letendre S, Ellis R, Heaton R, Patton S, Connor J, Samuels D, Hulgan T, Kallianpur A | | Date: 02-13-2017 | | Abstract:Background: Dysregulated central nervous system (CNS) iron transport has been implicated in neurocognitive (NC) disorders. We hypothesized that cerebrospinal fluid (CSF) biomarkers of CNS iron status are associated with changes in NC function over time in HIV-infected (HIV+) adults.
Methods: CSF iron, heavy-chain ferritin (H-ferritin) and transferrin were quantified in 403 participants in CHARTER, a prospective observational study of HIV+ adults who underwent comprehensive NC testing and assignment of a Global Deficit Score (GDS) at baseline and 6-month intervals up to 42 months (mos.). NC change status (improved/stable/declined) was defined at specific visits or last follow-up compared to baseline. Non-parametric statistical tests were used to test associations at baseline with GDS as a continuous variable, HIV disease or demographic factors. Biomarker associations with NC change status were evaluated by analysis of variance (ANOVA) or logistic regression to adjust for potential confounders such as age, comorbidity, and zidovudine (ZDV) use, which impacts iron transport. Repeated-measures ANOVA was performed to assess biomarker-GDS associations at 30, 36, and 42 mos. Analyses stratified by age and APOE-ε4 carrier status were also explored.
Results: Of 403 HIV+ adults with CSF biomarker data (22% aged≥50, 73% on ART, 68% with undetectable virus, 19% women), 157 completed follow-up at 30 mos., 131 at 36 mos., and 110 at 42 mos. CSF transferrin and H-ferritin were higher in men and participants aged≥50 years but were unrelated to APOE-ε4 status. Higher H-ferritin at baseline was associated with NC improvement at last follow-up in HIV+ adults aged<50, adjusting for age, comorbidity, ZDV use, and APOE-ε4 status, with relative risk 1.17 vs. stable status [p=0.01, 95% CI=1.03-1.33]. H-ferritin and transferrin were also associated with GDS differences at 30, 36 and 42 mos., adjusting for comorbidity [p<0.05 for both H-ferritin and transferrin; 0.5-1.1% of total GDS variance explained]. H-ferritin at baseline was also associated with better GDS in participants aged<50 at 30, 36, and 42 mos. (1.3% of GDS variance explained across visits). In APOE-ε4 carriers aged≥50 (N=10), CSF transferrin was associated with GDS at 30 mos., explaining 11.6% of the total GDS variance across visits.
Conclusions: CSF transferrin and ferritin are independently associated with NC change status and longitudinal GDS differences in HIV+ adults. Larger studies, including more older HIV+ adults, are needed to confirm these findings. |
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