Poorer Cognitive Performance in Perinatally HIV-Infected Children Versus Healthy Socioeconomically Matched Controls

Cohen, Sophie; Stege, Jacqueline A. ter; Geurtsen, Gert J.; Scherpbier, Henriëtte J.; Kuijpers, Taco W.; Reiss, Peter; Schmand, Ben; Pajkrt, Dasja

doi:10.1093/cid/ciu1144

Cited by 88 publications

(101 citation statements)

References 40 publications

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“…As we previously detected poorer cognitive functioning and structural cerebral injury in these HIV-infected children, 18,19 we expected that neurometabolite levels in this group differ from those in matched healthy controls and will be associated with HIV-related characteristics, cognitive functioning and neurodegenerative markers.…”

Section: Introductionmentioning

confidence: 80%

“…Perinatally HIV-infected children between 8 and 18 years of age, were recruited via the outpatient clinic of the Emma Children's Hospital in Amsterdam, and healthy children from the community, group-wise matched for gender, age, ethnicity and SES as previously described. 18 Participants were excluded if they had non-HIV related chronic neurological diseases, seizure disorders, intracerebral neoplasms or psychiatric disorders. The ethics committee of the Academic Medical Center in Amsterdam approved the study protocol.…”

Section: Methodsmentioning

confidence: 99%

“…18 Historical HIV viral loads (VL), CD4+ T-cell counts, Centers for Disease Control and Prevention (CDC) clinical staging and cART treatment history were derived from the Dutch HIV Monitoring Foundation database. CD4+ T-cell counts were transformed into Z-scores to correct for age and gender related differences.…”

Section: Methodsmentioning

confidence: 99%

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Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 80%

Section: Methodsmentioning

confidence: 99%

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Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

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“…A second procedure for overall classification is to perform a multivariate normative comparison (e.g., Cohen et al, 2015;González-Redondo et al, 2012;Smeding, Speelman, Huizenga, Schuurman, & Schmand, 2011;Su et al, 2015). In a multivariate comparison, it is determined whether an entire test profile-that is, an individual's combination of test scores-differs from that in the normative sample (Crawford & Allan, 1994;Grasman, Huizenga, & Geurts, 2010;Huba, 1985;Huizenga et al, 2007).…”

Section: Overall Classification As Impaired or Unimpairedmentioning

confidence: 99%

Normative comparisons for large neuropsychological test batteries: User-friendly and sensitive solutions to minimize familywise false positives

Huizenga

Rentergem

Grasman

et al. 2016

Journal of Clinical and Experimental Neuropsychology

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Introduction. In neuropsychological research and clinical practice, a large battery of tests is often administered to determine whether an individual deviates from the norm. We formulate three criteria for such large battery normative comparisons. First, familywise false-positive error rate (i.e., the complement of specificity) should be controlled at, or below, a prespecified level. Second, sensitivity to detect genuine deviations from the norm should be high. Third, the comparisons should be easy enough for routine application, not only in research, but also in clinical practice. Here we show that these criteria are satisfied for current procedures used to assess an overall deviation from the norm-that is, a deviation given all test results. However, we also show that these criteria are not satisfied for current procedures used to assess test-specific deviations, which are required, for example, to investigate dissociations in a test profile. We therefore propose several new procedures to assess such test-specific deviations. These new procedures are expected to satisfy all three criteria. Method. In Monte Carlo simulations and in an applied example pertaining to Parkinson disease, we compare current procedures to assess test-specific deviations (uncorrected and Bonferroni normative comparisons) to new procedures (Holm, one-step resampling, and step-down resampling normative comparisons). Results. The new procedures are shown to: (a) control familywise false-positive error rate, whereas uncorrected comparisons do not; (b) have higher sensitivity than Bonferroni corrected comparisons, where especially step-down resampling is favorable in this respect; (c) be user-friendly as they are implemented in a user-friendly normative comparisons website, and as the required normative data are provided by a database. Conclusion. These new normative comparisons procedures, especially step-down resampling, are valuable additional tools to assess test-specific deviations from the norm in large test batteries.

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“…In the presence of ART, HIV-1 infected infants present a range of neurodevelopmental delays and impairments, 47 which include fine and gross motor impairments, cognitive delays, 48,49 verbal comprehension deficits, 50,51 executive function impairments, 40,41 working memory deficits, impaired visual-spatial integration, 40 abnormal muscle tone, and spasticity. 30,32,33,38,40,43,52–56 A higher prevalence of seizure activity 57 and multiple-sclerosis-like illness have also been reported in perinatally infected infants.…”

Section: Neurodevelopmental Disordersmentioning

confidence: 99%

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Carryl¹,

Swang²,

Lawrence³

et al. 2015

ACS Chem. Neurosci.

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Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems.

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Poorer Cognitive Performance in Perinatally HIV-Infected Children Versus Healthy Socioeconomically Matched Controls

Cited by 88 publications

References 40 publications

Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

Normative comparisons for large neuropsychological test batteries: User-friendly and sensitive solutions to minimize familywise false positives

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

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