Title

The relationship between cerebrospinal fluid quinolinic acid levels and neuropsychological performance among HIV-1-seropositive individuals

Date of Award

1995

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Ray Winters, Committee Chair

Second Committee Member

Bonnie E. Levin, Committee Member

Abstract

Investigated the relationship between cerebrospinal fluid (CSF) concentrations of the endogenous excitotoxin, quinolinic acid (QUIN), and neuropsychological performance in 93 HIV-1-seropositive, English-speaking males whose primary risk factor for infection was homosexual intimate practices without a history of intravenous drug usage. Subjects ranged from 21 to 65 years old, had an average of 14.7 years of education, estimated average intelligence, and minimal depression. Subjects diagnosed with aseptic meningitis, CNS opportunistic infections, or cerebral neoplasms were excluded.Cross-sectional analyses compared CSF QUIN concentrations and neuropsychological performance between subjects with different manifestations of HIV-1-related disease according to CDC criteria (Asymptomatic, AIDS, AIDS dementia complex). Prospective analyses compared neuropsychological performance between subjects with normal-mild (less than 60 nmol/L) and moderate-high (greater than 60 nmol/L) elevations of CSF QUIN.Analyses of variance (ANOVA) revealed that CDC groups differed significantly on log10 CSF QUIN (p $<$.006) and in performance on neuropsychological measures of visuoconstructional abilities, visual and verbal memory, and reasoning.Correlational analyses controlling CDC status indicated that there was no relationship between CSF QUIN and age (p $<$ 67). Partial correlations controlling age, education, and depression revealed that log10 CSF QUIN concentrations were inversely related to neuropsychological measures of executive functioning, visual and verbal memory, and reasoning.Repeated measures ANOVAs with a one-between (QUIN group) and one-within (Time) design performed on neuropsychological measures at 3 time points over 2 years revealed significant main effects for QUIN groups on neuropsychological measures of verbal memory and executive functioning. No QUIN group x Time interaction effects were observed.These findings suggest that quinolinic acid may play a role in the cognitive dysfunction associated with HIV-1-infection. Future longitudinal investigations should examine whether QUIN antagonists are capable of reducing CSF QUIN concentrations and ameliorating cognitive dysfunction in HIV-1, concomitantly.

Keywords

Biology, Neuroscience; Psychology, Psychobiology; Biology, Animal Physiology; Psychology, Psychometrics; Health Sciences, Immunology

Link to Full Text

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