Low CSF leptin levels are associated with worse learning and memory performance in HIV-infected men.

OBJECTIVE: The main objective of this study was to investigate the association between human CSF leptin levels and neuropsychological (NP) performance in the setting of HIV infection. We hypothesized that human CSF leptin levels positively correlate with NP performance.BACKGROUND: Leptin is an adipocyte-derived hormone that influences brain development and function, particularly learning and memory, in the mouse model. The extent to which leptin contributes to neurocognitive functioning in humans is less clear.METHOD: A cross-sectional evaluation of CSF leptin and NP performance was performed. Leptin levels in CSF and serum samples from 59 HIV-positive men were measured by ELISA. Comprehensive, standardized NP testing was used to determine impairment status in global and specific domains.RESULTS: Lower CSF leptin levels and reduced leptin uptake into the central nervous system (CNS) correlated with impaired learning and memory performance in both univariate and multivariate analyses. In multivariate analyses, lower CSF leptin levels and reduced CNS leptin uptake were associated with worse NP performance in learning and memory, adjusting for CD4 nadir, antiretroviral treatment exposure, and HIV RNA levels in CSF.CONCLUSIONS: Low CSF leptin levels are associated with poorer performance in learning and memory among HIV-infected men adjusting for usual predictors of HIV-associated neurocognitive impairment. This association is consistent with prior in vitro and animal data suggesting leptin has a trophic or facilitatory role in the hippocampus, above and beyond its role in hypothalamic regulation.