Markers of macrophage activation and axonal injury are associated with prospective memory in HIV-1 disease

Objective: To use clinical specimens to better understand the neuropathogenesis of prospective memory (ProM) functioning in persons with HIV-1 infection. Background: Emergent evidence suggests that HIV-1 is associated with impaired ProM, but the underlying neuropathophysiology of this deficit is not known. Methods: Thirty-five nondemented subjects with HIV-1 infection completed measures of both ProM (ie, memory for future intentions) and retrospective memory (RM; ie, memory for past episodes). A panel of biomarkers reflecting several possible neuropathogenic mechanisms of HIV was measured in plasma and cerebrospinal fluid, including HIV-1 RNA, total tau, monocyte chemoattractant protein-1 (MCP-1), soluble receptor for tumor necrosis factor type II, and fibroblast growth factor 1. Results: After controlling for antiretroviral therapy and CD4 lymphocyte count, higher levels of MCP-1 in plasma, and soluble receptor for tumor necrosis factor type II and tau in cerebrospinal fluid were associated with ProM, but not RM. Markers of astrocytosis, growth factor depletion, and HIV-1 replication did not predict either ProM or RM. Conclusions: ProM impairment in HIV-1 may be dissociable from RM, perhaps reflecting specific neuropathogenic mechanisms of macrophage activation and axonal injury.