scholarly journals Neurocognitive Development in Perinatally Human Immunodeficiency Virus–infected Adolescents on Long-term Treatment, Compared to Healthy Matched Controls: A Longitudinal Study

2019 ◽  
Author(s):  
Malon Van den Hof ◽  
Anne Marleen ter Haar ◽  
Henriette J Scherpbier ◽  
Johanna H van der Lee ◽  
Peter Reiss ◽  
...  
Keyword(s):  
Working Memory ◽  
Human Immunodeficiency Virus ◽  
Executive Functioning ◽  
Processing Speed ◽  
Learning Ability ◽  
Z Score ◽  
Immunodeficiency Virus ◽  
Group Time ◽  
Visual Motor ◽  
Over Time

Abstract Background A cross-sectional analysis of the Neurological, cOgnitive and VIsual performance in hiv-infected Children cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated, perinatally human immunodeficiency virus (HIV)-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV−). In this longitudinal study, we compared cognitive development in the same adolescents over time. Methods We repeated the standardized cognitive test battery after a mean of 4.6 years (standard deviation 0.3). In participants who completed both assessments, we compared cognitive trajectories between groups in the domains of intelligence quotient (IQ), processing speed, working memory, executive functioning, learning ability, and visual-motor function, using linear mixed models. We explored associations with disease- and treatment-related factors and used multivariate normative comparison (MNC) to determine the prevalence of cognitive impairment. Results There were 21 PHIV+ and 23 HIV− participants that completed 2 assessments and were similar concerning age, sex, ethnicity, and SES. Compared to HIV− participants, in PHIV+ participants the IQ score increased significantly more over time (group*time 6.01, 95% confidence interval [CI] 1.5–10.50; P = .012), whereas executive functioning decreased significantly more (group*time −1.43 z score, 95% CI −2.12 to −0.75; P < .001), resulting in the disappearance and appearance of significant differences. Processing speed, working memory, learning ability, and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at an older age deviated more in executive functioning (−0.13 z score, 95% CI −0.24 to −0.02; P = .043). The prevalence of cognitive impairments by MNC was similar in both groups, at both time points. Conclusions The cART-treated PHIV+ adolescents appeared to have similar global cognitive development, compared to their healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.

scholarly journals Predictors of the Trajectory of Neurocognitive Functioning in the First Six Months after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3289-3289 ◽  
Author(s):  
Samantha J Mayo ◽  
Hans A. Messner ◽  
Sean B. Rourke ◽  
Doris Howell ◽  
J. Charles Victor ◽  
...  
Keyword(s):  
Working Memory ◽  
Stem Cell ◽  
Executive Functioning ◽  
Processing Speed ◽  
Acute Gvhd ◽  
Performance Status ◽  
Neurocognitive Functioning ◽  
Hematopoietic Stem ◽  
Psychomotor Efficiency ◽  
Over Time

Abstract Background: While most patients will not experience lasting neurocognitive effects from stem cell transplant, certain subgroups of patients may be particularly vulnerable to cognitive declines. The objective of this study was to identify factors that can predict the trajectory of neurocognitive functioning changes within the first six months after allogeneic hematopoietic stem cell transplantation (HCT). Methods: Adult patient scheduled for their first allogeneic HCT completed a neuropsychological test battery to assess neurocognitive functioning prior to transplant, and at 100 days and six months post-transplant. The neuropsychological testing battery consisted of six tests over 3 domains: learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory. Sociodemographic (e.g. intelligence quotient (IQ), years of education) and transplant-related (e.g. conditioning regimen, HCT-Comorbidity Index) characteristics were collected at baseline. Additional clinical characteristics were collected at each time point, including Karnofsky Performance Status, acute graft-versus-host disease (GVHD) graded using revised Glucksberg grading system, chronic GVHD graded with National Institutes of Health consensus criteria, and patient-reported outcomes of fatigue, depressive symptoms, and physical symptom distress. Raw scores were converted to standardized T-scores (Mean=50, SD=10) based on demographically-adjusted norms. Neurocognitive impairment was defined as performance of <1.5 SD on two tests or <2 SD on one test. Composite scores for each domain were tabulated based on average of scores on constituent tests. Participants who completed the baseline and at least one follow-up visit were included in the analysis. Unconditional growth models were used to assess for overall changes in neurocognitive functioning over time. Multivariate multilevel models were then specified to identify predictors of the trajectory of neurocognitive functioning. To address the issue of missing data, a sensitivity analysis was conducted in which all models were replicated using only the data from complete cases, or participants who were assessed at every time point. Results: 58 participants were included in the main analysis, 71% of whom provided data at all three time points. Missing data was mostly due to ill health preventing participation in study procedures. Mean age was 48.2 years; 47% were female; 81% of the sample was Caucasian. Mean years of formal education was 13.81 and the mean IQ was 114. The most frequent indications for allogeneic HCT included AML (34%), MDS (10%), CML (10%) and myelofibrosis (10%). 53% were treated with a myeloablative conditioning protocol. 46% of participants met the criteria for neuropsychological impairment prior to transplant. Mean T-scores of domain-specific neuropsychological performance prior to transplant were 39.93 (SD = 1.40) for learning/memory, 49.57 (SD = 1.26) for psychomotor efficiency/processing speed, and 49.37 (SD = 1.30) for executive functioning/working memory. Unconditional models specified overall improvements in learning/memory (3.64 units, p<.01), psychomotor efficiency/processing speed (3.44 units, p<.01), and executive functioning/working memory (3.82 units, p<.01) over the six months after transplant, that were not an effect of attrition. No significant change in the prevalence of overall impairment was detected over time. On multivariate analyses controlling for a range of sociodemographic and clinical predictors, Karnofsky Performance Status <80 was associated with worsening learning/memory over time (Figure 1); peak severity of acute GVHD higher than grade 2 was associated with worsening psychomotor efficiency/processing speed over time (Figure 2); and greater years of education predicted a faster improvement in psychomotor efficiency/processing speed over time. The effect of performance status and acute GVHD were maintained in subsequent sensitivity analyses. Conclusions: Overall, domain-specific neuropsychological performance demonstrated mild but statistically significantly improvement over the first six months after transplant. However, post-transplant outcomes, such as low functional status and severe acute GVHD, may influence the direction of change in neurocognitive functioning. Disclosures No relevant conflicts of interest to declare.

scholarly journals QOL-01. LONGITUDINAL COMPARISON OF NEUROCOGNITIVE TRAJECTORIES IN PEDIATRIC MEDULLOBLASTOMA PATIENTS TREATED WITH PROTON VERSUS PHOTON RADIOTHERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii431-iii431
Author(s):  
Lisa Kahalley ◽  
Rachel Peterson ◽  
M Douglas Ris ◽  
Laura Janzen ◽  
M Fatih Okcu ◽  
...  
Keyword(s):  
Working Memory ◽  
Processing Speed ◽  
Parental Education ◽  
Normal Brain ◽  
Treatment Protocols ◽  
Pediatric Medulloblastoma ◽  
Boost Dose ◽  
Perceptual Reasoning ◽  
Photon Radiotherapy ◽  
Over Time

Abstract PURPOSE By reducing dose to normal brain tissue, proton radiotherapy (PRT) may lessen neurocognitive risk traditionally associated with photon radiotherapy (XRT). We examined change in neurocognitive scores over time in pediatric medulloblastoma patients treated with PRT versus XRT. METHODS Neurocognitive scores from 79 patients (37 PRT, 42 XRT) were examined. Patients were treated between 2007–2018 on the same treatment protocols that differed only by craniospinal modality (PRT versus XRT). Change in scores over time since diagnosis were compared between groups. RESULTS Groups were similar on most demographic/clinical variables: sex (67.1% male), age at diagnosis (mean 8.6 years), CSI dose (median 23.4 Gy), length of follow-up (mean 4.3 years), and parental education (mean 14.3 years). Boost dose (p&lt;0.001) and margin (p=0.001) differed between groups. Adjusting for covariates, the PRT group exhibited superior outcomes in global IQ, perceptual reasoning, and working memory versus the XRT group (all p&lt;0.05). The XRT group exhibited significant decline in global IQ, working memory, and processing speed (all p&lt;0.05). The PRT group exhibited stable scores in all domains except processing speed (p=0.003). Posterior fossa syndrome imparted risk independent of modality. CONCLUSION This is the first study comparing neurocognitive trajectories between pediatric patients treated for medulloblastoma with PRT versus XRT on comparable, contemporary protocols. PRT was associated with more favorable neurocognitive outcomes in most domains compared to XRT, although processing speed emerged as vulnerable in both groups. This is the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.

scholarly journals Evolution of Envelope Sequences from the Genital Tract and Peripheral Blood of Women Infected with Clade A Human Immunodeficiency Virus Type 1

1998 ◽  
Vol 72 (10) ◽  
pp. 8240-8251 ◽  
Author(s):  
Mary Poss ◽  
Allen G. Rodrigo ◽  
John J. Gosink ◽  
Gerald H. Learn ◽  
Dana de Vange Panteleeff ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Peripheral Blood ◽  
Tissue Compartment ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Over Time

ABSTRACT The development of viral diversity during the course of human immunodeficiency virus type 1 (HIV-1) infection may significantly influence viral pathogenesis. The paradigm for HIV-1 evolution is based primarily on studies of male cohorts in which individuals were presumably infected with a single virus variant of subtype B HIV-1. In this study, we evaluated virus evolution based on sequence information of the V1, V2, and V3 portions of HIV-1 clade A envelope genes obtained from peripheral blood and cervical secretions of three women with genetically heterogeneous viral populations near seroconversion. At the first sample following seroconversion, the number of nonsynonymous substitutions per potential nonsynonymous site (dn) significantly exceeded substitutions at potential synonymous sites (ds) in plasma viral sequences from all individuals. Generally, values of dn remained higher than values of ds as sequences from blood or mucosa evolved. Mutations affected each of the three variable regions of the envelope gene differently; insertions and deletions dominated changes in V1, substitutions involving charged amino acids occurred in V2, and sequential replacement of amino acids over time at a small subset of positions distinguished V3. The relationship among envelope nucleotide sequences obtained from peripheral blood mononuclear cells, plasma, and cervical secretions was evaluated for each individual by both phylogenetic and phenetic analyses. In all subjects, sequences from within each tissue compartment were more closely related to each other than to sequences from other tissues (phylogenetic tissue compartmentalization). At time points after seroconversion in two individuals, there was also greater genetic identity among sequences from the same tissue compartment than among sequences from different tissue compartments (phenetic tissue compartmentalization). Over time, temporal phylogenetic and phenetic structure was detectable in mucosal and plasma viral samples from all three women, suggesting a continual process of migration of one or a few infected cells into each compartment followed by localized expansion and evolution of that population.

scholarly journals Sequential Turnover of Human Immunodeficiency Virus Type 1 env throughout the Course of Infection

2006 ◽  
Vol 80 (21) ◽  
pp. 10591-10599 ◽  
Author(s):  
Tara M. Riddle ◽  
Norah J. Shire ◽  
Marc S. Sherman ◽  
Kelly F. Franco ◽  
Haynes W. Sheppard ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Loss ◽  
Cd4 Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Over Time

ABSTRACT We examined the rates of variant population turnover of the V1-V2 and V4-V5 hypervariable domains of the human immunodeficiency virus type 1 (HIV-1) gp120 molecule in longitudinal plasma samples from 14 men with chronic HIV-1 infection using heteroduplex tracking assays (HTA). Six men had high rates of CD4+ T-cell loss, and eight men had low rates of CD4+ T-cell loss over 2.5 to 8 years of infection. We found that V1-V2 and V4-V5 env populations changed dramatically over time in all 14 subjects; the changes in these regions were significantly correlated with each another over time. The subjects with rapid CD4 loss had significantly less change in their env populations than the subjects with slow CD4 loss. The two subjects with rapid CD4 loss and sustained low CD4 counts (<150/μl for at least 2 years) showed stabilization of their V1-V2 and V4-V5 populations as reflected by low levels of total change in HTA pattern and low HTA indices (a novel measure of the emergence of new bands and band distribution); this stabilization was not observed in other subjects. The stabilization of env variant populations at low CD4 counts following periods of rapid viral evolution suggests that selective pressure on env, likely from new immune responses, is minimal when CD4 counts drop dramatically and remain low for extended periods of time.

scholarly journals COGNITIVE FUNCTIONING AMONG BREAST CANCER SURVIVORS AND NON-CANCER PARTICIPANTS: EVIDENCE FOR SIMILARITIES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S649-S650
Author(s):  
Giancarlo Pasquini ◽  
Brent J Small ◽  
Jacqueline Mogle ◽  
Martin Sliwinski ◽  
Stacey B Scott
Keyword(s):  
Breast Cancer ◽  
Working Memory ◽  
Executive Functioning ◽  
Cancer Survivors ◽  
Cognitive Functioning ◽  
Processing Speed ◽  
Breast Cancer Survivors ◽  
Cancer History ◽  
History Of ◽  
History Of Cancer

Abstract Breast cancer survivors may experience accelerated decline in cognitive functioning compared to same-aged peers with no cancer history (Small et al., 2015). Survivors may show important differences in mean-level performance or variability in cognitive functioning compared to those without a history of cancer (Yao et al., 2016). This study compared ambulatory cognitive functioning in a sample of breast cancer survivors and an age-matched community sample without a history of cancer (n_cancer=47, n_non-cancer=105, age range: 40-64 years, M=52.13 years). Participants completed three cognitive tasks measuring working memory, executive functioning, and processing speed up to five times per day for 14 days. Results indicated no mean-level differences in cognitive performance on the three tasks between cancer survivors and those without cancer history (p’s&gt;.05). Unexpectedly, women without cancer history showed more variability than survivors on working memory but not on the other two tasks. Across both groups, those without a college education performed worse on executive functioning (B=-0.05, SE=0.03, p&lt;.05) and working memory (B=0.94, SE=0.36, p&lt;.05) compared to those that completed college. Additionally, older age was associated with slower processing speed (B=31.67, SE=7.44, p&lt;.001). In sum, this study did not find mean-level group differences in cognitive functioning between cancer survivors and age-matched women without a history of cancer. Contrary to hypotheses, those without a history of cancer were more variable on working memory. Results suggested similarities in cognitive functioning in the two samples and that education and age are important predictors of cognitive functioning independent of cancer history.

scholarly journals The Reliability and Validity of the Action Fluency Test in Healthy College Students

2019 ◽  
Vol 34 (7) ◽  
pp. 1175-1191 ◽  
Author(s):  
Thomas P Ross ◽  
Sydne O’Connor ◽  
Graham Holmes ◽  
Brittany Fuller ◽  
Megan Henrich
Keyword(s):  
College Students ◽  
Working Memory ◽  
Information Processing ◽  
Executive Functioning ◽  
Processing Speed ◽  
Convergent Validity ◽  
Reliability And Validity ◽  
Information Processing Speed ◽  
Perceptual Reasoning ◽  
Fluency Test

Abstract Objective This study examined the test–retest reliability and construct validity of the Action Fluency Test (AFT) as a measure of executive functioning. Method Using a correlational design, 128 healthy college students (M Age = 19.24, SD = 2.01; M education = 13.29 years, SD = 0.81) completed the AFT, and measures of verbal and figural fluency, executive functioning and other relevant constructs (e.g., vocabulary, working memory, and attention). Results Coefficients of stability were acceptable for AFT correct words (r = .76; p &lt; .01), but not for errors (r = .41) or perseverations (r = .14). No practice effects were observed upon repeat testing (M interval = 39.21 days). Divergent validity evidence was mixed. AFT scores were unrelated to working memory and perceptual-reasoning abilities; however, correlations with vocabulary (r = .32; p &lt; .01) and information-processing speed (r = .30; p &lt; .01) were greater than associations between AFT scores and executive measures. Regarding convergent validity, AFT scores correlated with other fluency tasks (r = .4 range), but correlations with measures of executive functioning were absent or small. Action and letter fluency correlated with measures of attentional control and inhibition; however, these associations were no longer significant after controlling for shared variance with information-processing speed. Conclusions Findings are consistent with previous research suggesting vocabulary and information-processing speed underlie effective fluency performance to a greater extent than executive functioning. The AFT measures unique variance not accounted for by semantic and letter fluency tasks, and therefore may be used for a variety of research and clinical purposes.

scholarly journals Processing speed impairment in schizophrenia is mediated by white matter integrity

2014 ◽  
Vol 45 (1) ◽  
pp. 109-120 ◽  
Author(s):  
H. Karbasforoushan ◽  
B. Duffy ◽  
J. U. Blackford ◽  
N. D. Woodward
Keyword(s):  
Working Memory ◽  
White Matter ◽  
Executive Functioning ◽  
Functional Outcome ◽  
Processing Speed ◽  
Healthy Subjects ◽  
Verbal Learning ◽  
Group Differences ◽  
Neural Basis ◽  
Mediation Effects

BackgroundProcessing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter (WM) integrity in schizophrenia is unclear.MethodIndividuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory and executive functioning. Group differences in WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested.ResultsWM integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed but not in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed.ConclusionsCognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.

Aberrant and Unstable Expression of Immunoglobulin Genes in Persons Infected With Human Immunodeficiency Virus

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1317-1323 ◽  
Author(s):  
Alberto Bessudo ◽  
Laura Rassenti ◽  
Diane Havlir ◽  
Douglas Richman ◽  
Ellen Feigal ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Healthy Adults ◽  
Immunoglobulin Genes ◽  
Expression Levels ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Vh Gene ◽  
American Society ◽  
Over Time

We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VHgene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VHgene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens. © 1998 by The American Society of Hematology.

scholarly journals Longitudinal Development of Executive Functioning and Spoken Language Skills in Preschool-Aged Children With Cochlear Implants

2020 ◽  
Vol 63 (4) ◽  
pp. 1128-1147 ◽  
Author(s):  
William G. Kronenberger ◽  
Huiping Xu ◽  
David B. Pisoni
Keyword(s):  
Working Memory ◽  
Executive Functioning ◽  
Cochlear Implants ◽  
Language Skills ◽  
Verbal Working Memory ◽  
Spoken Language ◽  
Parent Report ◽  
Longitudinal Development ◽  
Spoken Language Skills ◽  
Over Time

Purpose Auditory deprivation has downstream effects on the development of language and executive functioning (EF) in prelingually deaf children with cochlear implants (CIs), but little is known about the very early development of EF during preschool ages in children with CIs. This study investigated the longitudinal development of EF and spoken language skills in samples of children with normal hearing (NH; N = 40) or CIs ( N = 41) during preschool ages. Method Participants were enrolled in the study between ages 3 and 6 years and evaluated annually up to the age of 7 years. Mixed-effects models were used to evaluate and predict growth of spoken language and EF skills over time. Results Children with CIs scored lower than NH peers on language measures but improved significantly over time. On performance-based neurocognitive measures of controlled attention, inhibition, and working memory, children with CIs scored more poorly than the sample of NH peers but comparable to norms, whereas on a parent report behavior checklist, children with CIs scored more poorly than both NH peers and norms on inhibition and working memory. Children with CIs had poorer EF than the sample of NH peers in most domains even after accounting for language effects, and language predicted only the verbal working memory domain of EF. In contrast, EF skills consistently predicted language skills at subsequent visits. Conclusions Findings demonstrate that, despite significant improvement over time, some domains of EF (particularly parent-reported EF) and language skills in children with CIs lag behind those of children with NH during preschool ages. Language delays do not fully explain differences in EF development between children with CIs and NH peers during preschool ages, but EF skills predict subsequent language development in children with CIs.

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