title: Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children.
abstract: Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36).Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses.HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. There were no associations between neurometabolites and neuronal damage markers in blood or CSF.Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.
authors.affiliation: From the Department of Pediatric Hematology, Immunology and Infectious Diseases, (YWVD, CB, SC, JATS, HJS, TWK, DP); Psychosocial Department (JATS), Emma Children's Hospital/Academic Medical Center; Neurochemistry Laboratory and Biobank (CET), Department of Clinical Chemistry, VU University Medical Center and Neurocampus Amsterdam, the Netherlands; Neurology (JK), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland; Department of Experimental Immunology (NAK); Department of Global Health and Amsterdam Institute of Global Health and Development (PR), Academic Medical Center; HIV Monitoring Foundation (PR); Department of Internal Medicine (PR), Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA); and Department of Radiology (CBLMM, MWAC), Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Van Dalen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Blokhuis
authors.forename: Sophie
authors.initials: S
authors.lastname: Cohen
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Ter Stege
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Henriette J
authors.initials: HJ
authors.lastname: Scherpbier
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Charles B L M
authors.initials: CBLM
authors.lastname: Majoie
authors.forename: Matthan W A
authors.initials: MWA
authors.lastname: Caan
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
mesh_terms: D015526:AIDS Dementia Complex / Q000175:diagnosis*; D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D018791:CD4 Lymphocyte Count; D002648:Child; D002794:Choline / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis*; D015331:Cohort Studies; D003401:Creatine / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D015658:HIV Infections / Q000151:congenital* / Q000175:diagnosis / Q000635:transmission*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D007294:Inositol / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D009483:Neuropsychological Tests; D012016:Reference Values; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016900:Neurofilament Proteins; D016875:tau Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline