title: Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.
abstract: Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Renee Donahue
authors.initials: RD
authors.lastname: Carlson
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Rolfes
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Birkenkamp
authors.affiliation: Infectious Disease Institute, School of Medicine, Department of Medicine, Kampala, Uganda.|Makerere University College of Health Sciences, School of Medicine, Department of Medicine, Kampala, Uganda.|Makerere University College of Health Sciences, School of Medicine, Department of Psychiatry, Kampala, Uganda.
authors.forename: Noeline
authors.initials: N
authors.lastname: Nakasujja
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.|Infectious Disease Institute, School of Medicine, Department of Medicine, Kampala, Uganda.
authors.forename: Radha
authors.initials: R
authors.lastname: Rajasingham
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.|Infectious Disease Institute, School of Medicine, Department of Medicine, Kampala, Uganda.|Makerere University College of Health Sciences, School of Medicine, Department of Medicine, Kampala, Uganda.
authors.forename: David B
authors.initials: DB
authors.lastname: Meya
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D003072:Cognition Disorders / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult