Cognitive Impairment In Survivors Research Articles

Limited contribution of the of P2X4 receptor to LPS-induced microglial reaction in mice.

Sepsis is life-threatening condition that can trigger long-term neurological sequelae, including cognitive impairment in survivors. The pathogenesis of the so-called sickness behavior is poorly understood, but sepsis-driven neuroinflammation is thought to play a key role. Microglia are the central nervous system resident immune cells and play major roles in the induction and the control of neuroinflammatory processes. Accordingly, we recently demonstrated important microglia reaction, characterized by dramatic microglia transcriptome remodeling, in an experimental model of sepsis. Interfering with microglia pathways thus represents an interesting opportunity to tune microglia reaction towards beneficial outcomes. Purinergic signaling is central to microglia biology and controls key microglia functions. In particular, P2X4 receptors, which are highly permeable to calcium and de novo expressed in reactive microglia, seem to be an interesting target to modulate microglia reaction. Here, we investigated the impact of P2X4 receptors on the LPS-driven microglia transcriptome remodeling. Although we used complementary and sensitive biostatistical approaches, we did not measure significant impact of P2X4 deficiency onto microglia transcriptome either in homeostatic nor reactive condition. Overall, our results revealed that microglia reaction elicited by LPS-mediated sepsis is P2X4 independent and highlights the functional diversity of microglia reaction. These results also promote for the search of disease-specific targets to tune microglia reaction towards beneficial outcomes.

5 The Impact of Sex and Associations With Treatment Exposures on Neurocognitive Impairment in Pediatric Cancer Survivors: A report from the Childhood Cancer Survivor Study

Objective:Sexual dimorphism in human brain structure and behavior is influenced by exposure to sex hormones during critical developmental periods. In children, cancer and cancer treatments may alter hormone activity and brain development, impacting neurocognitive functions.Participants and Methods:Five-year survivors of childhood cancer (N=15,560) diagnosed at <21 years from 1970 to 1999, and 3,206 siblings from the Childhood Cancer Survivor Study completed the Neurocognitive Questionnaire (NCQ), a measure of self-reported task efficiency (TE), emotion regulation (ER), Organization, and working memory (WM). We compared rates of cognitive impairment (i.e., NCQ scores >90th percentile) in survivors and same-sex siblings, and sex differences in risk factors for cognitive impairment (i.e., treatment exposures, chronic health conditions (CHCs), cancer diagnosis, age at diagnosis) using modified Poisson regressions.Results:Survivors were more likely to report cognitive impairment than same-sex siblings (Males: TE OR=2.3, p<.001; ER OR=1.7, p=.008; Organization OR=1.5, p=.04; WM OR=2.3, p<.001. Females: TE OR=2.6, p<.001; ER OR=1.9, p<.001; Organization OR=1.5, p=.02; WM OR=2.6, p<.001). Within survivors, females were more likely than males to report impairment in TE (OR=1.2, p=.001), ER (OR=1.5, p<.001), and WM (OR=1.2, p<.001). There were no sex differences in symptom severity in siblings (all ps>.05). Risk factors for cognitive impairment in survivors included cranial radiation dose (TE <20Gy OR=1.5, p=.008, ≥20Gy OR=2.5, p<.001; ER OR=1.5, p<.001; Organization <20 Gy OR=1.4, p<.001; < WM 20 Gy OR=1.8, p<.001, ≥20Gy OR=2.7, p<.001), presence of moderate to severe CHCs (TE 1 CHC OR=1.9, p<.001, >1 CHC OR=3.6, p<.001; ER 1 CHC OR=1.7, p<.001, >1 CHC OR=2.2, p<.001; Organization 1 CHC OR=1.5, p=.001, >1 CHC OR=2.5, p<.001; WM 1 CHC OR=1.8, p<.001, >1 CHC OR=4.1, p<.001). There were sex differences in cognitive impairment risk factors in survivors. In females, cranial radiation dose (<20 Gy TE OR=1.6, p=.02; ≥20Gy TE OR=1.4, p=.01), leukemia diagnosis (TE OR=1.4, p=.02), or diagnosis age between 3-5 years (WM OR=1.4, p=.02) conferred higher risk for cognitive impairment compared to males with the same history. Females diagnosed with Hodgkin’s lymphoma (Organization OR=0.61, p=.05) or non-Hodgkin’s lymphoma (Organization OR=0.55, p=.03) were at lower risk for cognitive impairment compared to males.Conclusions:We found sex-specific differences in rates of, and risk factors for, neurocognitive impairment, suggesting a sex vulnerability. Future studies examining interactions between sex hormones and treatment exposures during brain development will enable tailoring treatments follow-up interventions to ensure that quality of life is maximized.

Train-your-brain program to reduce depression, anxiety, and stress in stroke survivors: a pilot community-based cognitive intervention study.

Stroke is a major cause of death and disability worldwide, and it often results in depression, anxiety, stress, and cognitive impairment in survivors. There is a lack of community-based cognitive interventions for stroke survivors. This pilot single trial aimed to assess the feasibility, acceptability, and perceived effectiveness of a community-based cognitive intervention program called Train-Your-Brain (TYB) for stroke survivors and caregivers. The study focused on improvements in emotional and psychological well-being, as well as cognitive functioning. A quasi-experimental design was used in this study. A total of 48 participants were recruited and assessed using Depression, Anxiety, Stress Scale - 21 items (DASS-21), Montreal Cognitive Assessment (MoCA) and Symbol Digits Modality Test (SDMT) before and after the intervention. The TYB program consisted of nine sessions and was conducted via the Zoom software application. Participants provided feedback on the program, highlighting areas for improvement. Twenty-seven stroke survivors and 21 caregivers completed the program. Participants expressed high satisfaction with the TYB program but recommended avoiding assessments in December and customizing the program for stroke survivors and caregivers. Stroke survivors showed significant improvements in depression and stress scores, while caregivers experienced no significant improvements after the program. While there was a slight improvement in stroke survivors' cognitive scores after the program, it was not statistically significant. Caregivers, however, experienced a significant decline in cognitive scores. The TYB program provided group support and validation, resulting in improved mood and reduced stress among stroke survivors. Cultural collectivism played a significant role in fostering group cohesion. However, the program's limited focus on caregivers and timing of assessments during the December holidays may have affected the outcomes. The TYB program demonstrated feasibility and potential effectiveness in alleviating psychological distress and enhancing cognitive function among stroke survivors. Future research should explore long-term effects, larger sample sizes, and non-English-speaking populations to enhance generalizability. Tailored interventions for caregivers are necessary.

Prevalence of Cognitive Impairment and Dementia After Intracerebral Hemorrhage.

To study the prevalence of cognitive impairment in survivors of intracerebral hemorrhage (ICH). Survivors of spontaneous ICH were followed up in the neurology outpatient department when they reported for follow-up after 6 months. Neuroimaging records at the onset and at follow-up visits are studied for the location of ICH, volume of ICH, intraventricular extension, and hydrocephalus. The volume of ICH is calculated by ABC/2 method on a CT scan. All patients underwent cognitive assessment with Addenbrooke's cognitive examination ACE III and were categorized as patients having cognitive impairment (or) no cognitive impairment. A total of 120 patients were studied, out of which 77 (64%) are males and 43 (36%) are females with age groups ranging from 26 to 75 years. In the study population, the mean age was found to be 62.3 years. Specifically, the mean age for males was 56.9 years, while for females it was 63.4 years. Cognitive impairment was noted in 34 of 120 patients (28%) during 6 to 12 months of examination, of which 11 of 19 were in lobar location, 21 of 94 were in sub-cortical location, and 2 of 7 were in infratentorial location. It was found that 28% of survivors of ICH were cognitively impaired. Hence, it is essential to assess cognition in post-ICH patients during follow-up, so that suitable adjustments can be made in their employment, and also in educating family members in providing a good quality of life.

Instruments Assessing Cognitive Impairment in Survivors of Critical Illness and Reporting of Race Norms: A Systematic Review.

A comprehensive search was conducted in PubMed (National Center for Biotechnology Information), Excerpta Medica dataBASE (Ovid), Psychological Information Database (ProQuest), and Web of Science (Clarivate) for English language studies published since 2002. Studies were eligible if the population included adult ICU survivors assessed for postdischarge cognitive outcomes. Two independent reviewers screened abstracts, examined full text, and extracted data from all eligible articles. A total of 98 articles (55 unique cohorts: 22 general ICU, 14 Acute respiratory distress syndrome/Acute respiratory failure/Sepsis, 19 COVID-19 and other subpopulations) were eligible for data extraction and synthesis. Among general ICU survivors, the majority of studies (n = 15, 68%) assessed cognition using multiple instruments, of which the most common was the Mini-Mental State Examination. Only nine of the 22 studies (41%) explicitly reported using patient demographic norms for scoring neuropsychological cognitive tests. Of the nine, all reported using age as a norming characteristic, education was reported in eight (89%), sex/gender was reported in five (55%), and race/ethnicity was reported in three (33%). Among Acute respiratory distress syndrome/Acute respiratory failure/Sepsis survivors, norming characteristics were reported in only four (28%) of the 14 studies, of which all reported using age and none reported using race/ethnicity. Less than half of the studies measuring cognitive outcomes in ICU survivors reported the use of norming characteristics. There is substantial heterogeneity in how studies reported the use of cognitive instruments, and hence, the prevalence of the use of patient norms may be underestimated. These findings are important in the development of appropriate standards for use and reporting of neuropsychological tests among ICU survivors.

Cancer‐related cognitive impairment in survivors of adolescent and young adult non‐central nervous system cancer: A scoping review

Cancer-related cognitive impairments (CRCI) are common after treatment and can have important impacts on the lives of adolescent and young adult (AYA) cancer survivors-those cancer survivors diagnosed between ages 15 and 39. However, most research focuses on survivors diagnosed under age 15 or over age 39 so we know relatively little about CRCI among AYA survivors of non-central nervous system (CNS) cancers. Here we review the research on CRCI among AYA survivors of non-CNS cancers to determine prevalence, associated factors, and impact on survivors' lives as well as implications for future research. In November 2021 we performed a systematic search of the literature in MEDLINE, Web of Science, PsycInfo, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials to identify peer-reviewed English language articles describing original research with at least one cognitive outcome and conducted with AYA survivors of non-CNS cancer diagnosed as AYAs. We screened 6003 articles and 21 met eligibility criteria. Guided by the PRISMA-ScR Checklist, we extracted study information to meet review objectives. Most studies employed cross-sectional surveys or interviews, though some employed longitudinal methods, neurocognitive assessments, or brain imaging. From the subset of articles that reported a prevalence we calculated a weighted mean prevalence of 25.75% and weighted median prevalence of 27.8%. The factors associated with CRCI included female gender, higher dose chemotherapy, and comorbidities. CRCI impacted the lives of AYA survivors through impaired role functioning, financial toxicity, and unmet needs. CRCI is highly prevalent among non-CNS cancer survivors diagnosed as AYAs and impacts quality of life and role functioning. This review suggests a need for further longitudinal, imaging, and mixed methods research and provision of resources to help achieve better quality of life and educational and occupational attainment during what is potentially a decades-long survivorship period. However, although interventions might improve cognition and functioning, the review identified only one pilot study. Digital interventions may be a practical and effective option for this age group, but they have yet to be adequately investigated.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3months after discharge. Methods: 13 ARF survivors (mean age 51years and 69% males) completed actigraphy and sleep diaries for 9days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats

Sepsis causes overproduction of inflammatory cytokines, organ dysfunction, and cognitive impairment in survivors. In addition to inflammation, metabolic changes occur according to the stage and severity of the disease. Understanding the role and place of metabolic disturbances in the pathophysiology of sepsis is essential to evaluate the framework of septic patients, predict the syndrome progress, and define the treatment strategies. We investigated the effect of simvastatin on the disease time course and on metabolic alterations, especially with respect to their possible consequences in the CNS of surviving rats. The animals of this study were weighed daily and followed for 10days to determine the survival rate. In the first experiment, control or cecal ligation and puncture (CLP)-animals were randomized in 24h, 48h, and 10days after septic induction, for bacterial load determination and quantification of cytokines. In the second experiment, control or CLP-animals were treated or not with simvastatin and randomized in the same three time points for cytokines quantification and assessment of their body metabolism and locomotor activity (at 48h and 10days), as well as the evaluation of cytoarchitecture and astrogliosis (at 10days). The CLP-rats treated with simvastatin showed a reduction in plasma cytokines and improvement in metabolic parameters and locomotor activity, followed by minor alterations compatible with apoptosis and astrogliosis in the hippocampus and prefrontal cortex. These results suggest that the anti-inflammatory effect of simvastatin plays a crucial role in restoring energy production, maintaining a hypermetabolic state necessary for the recovery and survival of these CLP-rats.

One-Year Trajectory of Cognitive Changes in Older Survivors of COVID-19 in Wuhan, China

Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy. To investigate the 1-year trajectory of cognitive changes in older COVID-19 survivors. This cohort study recruited 3233 COVID-19 survivors 60 years and older who were discharged from 3 COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. Their uninfected spouses (N = 466) were recruited as a control population. Participants with preinfection cognitive impairment, a concomitant neurological disorder, or a family history of dementia were excluded, as well as those with severe cardiac, hepatic, or kidney disease or any kind of tumor. Follow-up monitoring cognitive functioning and decline took place at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was categorized as severe or nonsevere following the American Thoracic Society guidelines. The main outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40, respectively. Based on the cognitive changes observed during the 2 periods, cognitive trajectories were classified into 4 categories: stable cognition, early-onset cognitive decline, late-onset cognitive decline, and progressive cognitive decline. Multinomial and conditional logistical regression models were used to identify factors associated with risk of cognitive decline. Among the 3233 COVID-19 survivors and 1317 uninfected spouses screened, 1438 participants who were treated for COVID-19 (691 male [48.05%] and 747 female [51.95%]; median [IQR] age, 69 [66-74] years) and 438 uninfected control individuals (222 male [50.68%] and 216 female [49.32%]; median [IQR] age, 67 [66-74] years) completed the 12-month follow-up. The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower Telephone Interview of Cognitive Status-40 scores than those with nonsevere cases and control individuals at 12 months (median [IQR]: severe, 22.50 [16.00-28.00]; nonsevere, 30.00 [26.00-33.00]; control, 31.00 [26.00-33.00]). Severe COVID-19 was associated with a higher risk of early-onset cognitive decline (odds ratio [OR], 4.87; 95% CI, 3.30-7.20), late-onset cognitive decline (OR, 7.58; 95% CI, 3.58-16.03), and progressive cognitive decline (OR, 19.00; 95% CI, 9.14-39.51), while nonsevere COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.71; 95% CI, 1.30-2.27) when adjusting for age, sex, education level, body mass index, and comorbidities. In this cohort study, COVID-19 survival was associated with an increase in risk of longitudinal cognitive decline, highlighting the importance of immediate measures to deal with this challenge.

Assessment of Cognitive Impairment in Survivors of Breast Cancer: A Cross-sectional Study

Resumo Estudo prospectivo e transversal, para determinar a prevalência de prejuízo cognitivo decorrente da quimioterapia e explorar fatores preditores e mediadores em sobreviventes de câncer de mama. Utilizou-se o Termômetro de Distress, Escala de Ansiedade e Depressão, Functional Assessment of Chronic Illness Therapy-General e Cognitive Function. As sobreviventes (N = 62) reportaram uma alta prevalência de distress (46,8%) e de ansiedade (24,2%), com baixos escores nas subescalas déficit cognitivo e habilidades cognitivas percebidos. O funcionamento cognitivo esteve associado à idade (β = 1,42; p = 0,002), atuação profissional (β = -23,12; p = 0,004), depressão (β = -5,43; p = 0,001) e qualidade de vida (β = 1,24; p = 0,001). Prejuízo cognitivo deve ser considerado no serviço de Psico-Oncologia.

Assessment of Cognitive Function in Patients After COVID-19 Infection

People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association with disease severity are not well characterized. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning.1 We investigated rates of cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency department (ED), or inpatient hospital settings.

Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy with a global incidence of approximately 1 to 8 per 1,000 live births. Neonatal encephalopathy can cause neurodevelopmental and cognitive impairments in survivors of hypoxic-ischemic insults with and without functional motor deficits. Normal neurodevelopmental outcomes in early childhood do not preclude cognitive and behavioral difficulties in late childhood and adolescence because cognitive functions are not yet fully developed at this early age. Therapeutic hypothermia has been shown to significantly reduced death and severe disabilities in term newborns with HIE. However, children treated with hypothermia therapy remain at risk for cognitive impairments and follow-up is necessary throughout late childhood and adolescence. Novel adjunctive neuroprotective therapies combined with therapeutic hypothermia may enhance the survival and neurodevelopmental outcomes of infants with HIE. The extent and severity of brain injury on magnetic resonance imaging might predict neurodevelopmental outcomes and lead to targeted interven tions in children with a history of neonatal encephalopathy. We provide a summary of the long-term cognitive outcomes in late childhood and adolescence in children with a history of HIE and the association between pattern of brain injury and neurodevelopmental outcomes.

Effects of metabolic syndrome on cognitive outcomes in long-term survivors of childhood cancer.

12013 Background: Childhood cancer therapy increases risk for cognitive impairment and other chronic conditions, which also may impact cognition. We assessed the unique impact of metabolic syndrome (MetS) on cognition in survivors participating in the St. Jude Lifetime Cohort Study. Methods: Participants included 4058 survivors of childhood cancer (53.9% female; mean [SD] age 30.1 [10.5] years at evaluation; 22.6 [10.1] years from diagnosis) who completed clinical evaluation and cognitive testing. MetS criteria followed Adult Treatment Panel III guidelines (at least 3 of: hypertension, high triglycerides, abdominal obesity, low high-density lipoprotein [HDL], high fasting glucose). Multivariable log-binomial regression models assessed risk of cognitive impairment associated with MetS stratified by survivors who did (n = 2301) or did not (n = 1757) receive central nervous system (CNS)-directed therapy. Mediation analysis assessed effects of MetS and physical activity in cranial radiotherapy (CRT)-associated cognitive impairment. Models were adjusted for age, sex, follow-up time and treatment exposures. Results: MetS was associated with increased risk of impaired attention (relative risk [RR] 1.34 95% confidence interval [CI] 1.07-1.66), processing speed (RR 1.25 CI 1.11-1.41) and executive function (RR 1.18 CI 1.01-1.37) in survivors with CNS-directed therapy and academic achievement (RR 1.84 CI 1.18-2.89), attention (RR 1.43 CI 1.10-1.87), and processing speed (RR 1.46 CI 1.21-1.75) in those without CNS-directed therapy. MetS components associated with cognitive impairment included abdominal obesity (memory RR 1.34 CI 1.13-1.59; processing speed RR 1.41 CI 1.24-1.59; executive function RR 1.21 CI 1.05-1.39) and low HDL (intelligence RR 1.26 CI 1.06-1.49; attention RR 1.27 CI 1.03-1.57; processing speed RR 1.17 CI 1.01-1.35; executive function RR 1.20 CI 1.05-1.37) in survivors with CNS-directed therapy. In survivors treated without CNS-directed therapy hypertension (academic achievement RR 1.49 CI 1.18-1.88; intelligence RR 1.34 CI 1.02-1.76; attention RR 1.42 CI 1.12-1.79; memory RR 1.45 CI 1.14-1.84; processing speed RR 1.30 CI 1.08-1.55; executive function RR 1.32 CI 1.08-1.62) and abdominal obesity (academic achievement RR 1.71 CI 1.07-2.72; processing speed RR 1.23 CI 1.02-1.49; executive function RR 1.38 CI 1.09-1.75) were associated with impairment. In mediation analyses, direct effects of CRT were identified, as were indirect effects through physical activity (processing speed β = 0.035 p < 0.01; attention β = 0.03 p < 0.01; executive function β = 0.172 p < 0.01). Conclusions: MetS increases risk of cognitive impairment in survivors, particularly abdominal obesity, hypertension and low HDL. Physical activity appears to partially mediate impact of CRT on cognitive outcomes and is an important target for interventions to lower impairment risk.

Cognitive Impairment in Survivors of Pediatric Acute Lymphoblastic Leukemia Treated With Chemotherapy Only.

Article Tools REVIEW ARTICLES Neurocognitive Outcomes in Survivors of Pediatric Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.02322 Journal of Clinical Oncology - published online before print April 22, 2021 PMID: 33886368 Cognitive Impairment in Survivors of Pediatric Acute Lymphoblastic Leukemia Treated With Chemotherapy Only Ellen van der Plas , PhD1xEllen van der PlasSearch for articles by this author; Arunkumar J. Modi, MBBS, MPH2xArunkumar J. ModiSearch for articles by this author; Chi Kong Li , MBBS, MD3,4,5xChi Kong LiSearch for articles by this author; Kevin R. Krull , PhD6,7xKevin R. KrullSearch for articles by this author; and Yin Ting Cheung , PhD8xYin Ting CheungSearch for articles by this author Show More 1Department of Psychiatry, University of Iowa Hospital & Clinics, Iowa, IA2Stead Family Department of Pediatrics, University of Iowa, Iowa, IA3Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China4Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China5Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, China6Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN7Department of Psychology, St Jude Children's Research Hospital, Memphis, TN8School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China https://doi.org/10.1200/JCO.20.02322 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveThe goal of this review is to provide an up-to-date summary of current evidence regarding neurocognitive outcomes in survivors of pediatric acute lymphoblastic leukemia treated with chemotherapy only. Limitations and controversies are highlighted, and directions for future research are discussed.Knowledge GeneratedImpairments in attention, fine motor skill, processing speed, mathematics, and executive functions have consistently been identified in survivors of pediatric acute lymphoblastic leukemia. Risk factors of neurocognitive impairment can broadly be categorized into demographic (eg, young age at diagnosis), treatment characteristics (eg, exposure to high-dose methotrexate), genetic modulators (eg, polymorphism folate pathway genes), and physical complications during treatment (eg, sepsis).RelevanceThe field is now poised to identify mechanisms of neurocognitive deficits, which is necessary in the development of targeted strategies of mitigation, remediation, and prevention. Using data from large, multinational, longitudinal studies may help develop prediction models for this complex phenotype.SUPPORTSupported in part by the Hong Kong Research Grant Council (ref no: 24614818) awarded to Y.T.C.AUTHOR CONTRIBUTIONSConception and design: Ellen van der Plas, Arunkumar J. Modi, Chi Kong Li, Kevin R. Krull, Yin Ting CheungFinancial support: Yin Ting CheungCollection and assembly of data: Ellen van der Plas, Chi Kong Li, Yin Ting CheungData analysis and interpretation: Ellen van der Plas, Arunkumar J. Modi, Chi Kong Li, Yin Ting CheungManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTCognitive Impairment in Survivors of Pediatric Acute Lymphoblastic Leukemia Treated With Chemotherapy OnlyThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Chi Kong LiConsulting or Advisory Role: Amgen AsiaKevin R. KrullPatents, Royalties, Other Intellectual Property: Royalties from Wolters KluwerNo other potential conflicts of interest were reported.

Cognitive Impairment in Survivors of Pediatric Extracranial Solid Tumors and Lymphomas

Article Tools REVIEW ARTICLES Neurocognitive Outcomes in Survivors of Pediatric Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.02358 Journal of Clinical Oncology - published online before print April 22, 2021 PMID: 33886354 Cognitive Impairment in Survivors of Pediatric Extracranial Solid Tumors and Lymphomas Rebecca Foster , PhD1,2xRebecca FosterSearch for articles by this author; Daniel J. Zheng, MD, MHS3xDaniel J. ZhengSearch for articles by this author; Kelli L. Netson-Amore , PhD4xKelli L. Netson-AmoreSearch for articles by this author; and Nina S. Kadan-Lottick , MD, MSPH5xNina S. Kadan-LottickSearch for articles by this author Show More 1St Louis Children's Hospital, St Louis, MO2Washington University, St Louis, MO3Boston Children's Hospital, Boston, MA4University of Kansas School of Medicine-Wichita, Wichita, KS5Yale University School of Medicine and Yale Cancer Center, New Haven, CT https://doi.org/10.1200/JCO.20.02358 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveAre cognitive outcomes impaired in survivors of childhood extracranial solid tumors and lymphomas? In our critical review of the literature, we explored cognitive functioning after specific extracranial solid tumor and lymphoma diagnoses, discussed possible associated risk factors, highlighted research gaps, and provided clinical guidance for affected survivors.Knowledge GeneratedExisting studies suggest that survivors of osteosarcoma, neuroblastoma, Wilms tumor, non-Hodgkin lymphoma, Hodgkin lymphoma, and Langerhans cell histiocytosis have increased risk of cognitive impairment. Co-morbid health conditions were frequently associated with cognition.RelevanceGiven the older age at diagnosis of many childhood extracranial solid tumors and lymphomas as well as toxicities associated with certain therapies, patients may benefit from vocational services, occupational therapy, physical therapy, and/or hearing or visual rehabilitation in addition to surveillance for cognitive difficulties.AUTHOR CONTRIBUTIONSConception and design: Rebecca Foster, Kelli L. Netson-Amore, Nina S. Kadan-LottickAdministrative support: Nina S. Kadan-LottickCollection and assembly of data: Daniel J. Zheng, Kelli L. Netson-Amore, Nina S. Kadan-LottickData analysis and interpretation: Daniel J. ZhengManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTCognitive Impairment in Survivors of Pediatric Extracranial Solid Tumors and LymphomasThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Nina S. Kadan-LottickHonoraria: Medtronic, Boston ScientificConsulting or Advisory Role: Medtronic, Boston ScientificSpeakers' Bureau: Medtronic, Boston ScientificNo other potential conflicts of interest were reported.

Estado cognitivo y funcional a largo plazo en supervivientes de una hemorragia subaracnoidea aneurismática: análisis de una cohorte retrospectiva

ObjectiveLittle data is available on long-term functional and cognitive outcomes in patients with aneurysmal subarachnoid hemorrhage (ASH). The main objective of this study was to assess cognition, functional state, mood disorders, and quality of life in patients with SAH at least six months following the ASH. Patients and methodsCross-sectional study of 40 patients (aged 58.2 [SD 9.9] years) with ASH, discharged from a Neurologic Rehabilitation unit between January 2010 and July 2017. Main outcome variables: functional status (Barthel index), cognition (Pfeiffer questionnaire), depression (Hamilton scale), and health-related quality of life (European Quality of Life-5 Dimensions [EQ-5D]), as well as type and duration of therapeutic rehabilitation procedures after discharge. ResultsFrom 35 patients with cognitive disorders, only 12 received cognitive therapy at hospital discharge. In the long-term follow-up, cognitive impairment persisted in 22 patients. When compared with those without cognitive impairment, they presented significantly worse mean differences in the Barthel index (15.5 [95% CI: 1.2-29.7]), Hamilton scale (-0.8 [95% CI: -1.27 to -0.37]), and EQ-5D (27.6 [95% CI: 12.4-19]). ConclusionThe prevalence of long-term cognitive impairments in survivors of a SAH episode is high, and their presence is associated with worse functional status, more depression and worse quality of life. The low percentage of subjects who received cognitive therapies through their recovery process and the clinical implications observed, support the need of including neuropsychological therapies in the rehabilitation programs after an SAH event.

White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies.

Intraventricular haemorrhage (IVH) continues to be a major complication of prematurity that can result in cerebral palsy and cognitive impairment in survivors. No optimal therapy exists to prevent IVH or to treat its consequences. IVH varies in severity and can present as a bleed confined to the germinal matrix, small-to-large IVH or periventricular haemorrhagic infarction. Moderate-to-severe haemorrhage dilates the ventricle and damages the periventricular white matter. This white matter injury results from a constellation of blood-induced pathological reactions, including oxidative stress, glutamate excitotoxicity, inflammation, perturbed signalling pathways and remodelling of the extracellular matrix. Potential therapies for IVH are currently undergoing investigation in preclinical models and evidence from clinical trials suggests that stem cell treatment and/or endoscopic removal of clots from the cerebral ventricles could transform the outcome of infants with IVH. This Review presents an integrated view of new insights into the mechanisms underlying white matter injury in premature infants with IVH and highlights the importance of early detection of disability and immediate intervention in optimizing the outcomes of IVH survivors.

Cancer-related cognitive impairment in survivors of acute lymphoblastic leukemia

Cancer-related cognitive impairment in survivors of acute lymphoblastic leukemia

Abstract 275: Cardiac Arrest Etiology and Associated Cognitive Impairment in Survivors

Background: Cardiac arrest is a significant public health problem, impacting over 500,000 people in the United States annually. The four major etiologies of arrest are cardiac, respiratory, traumatic, and other. The objective was to determine the impact of etiology on cognition in cardiac arrest survivors using the Montreal Cognitive Assessment (MOCA). Hypothesis: Cardiac arrest etiology impacts cognitive exam score, and patient demographics and characteristics modify that relationship. Methods: A retrospective cohort analysis was performed on all Pittsburgh Post Cardiac Arrest Service (PCAS) patients from 2012-18. Data were acquired through medical record review. T-tests, linear and logistic regression were used to assess the relationships between exam score and modifying factors. MOCA score was analyzed as a binomial variable using a pass/fail threshold of 26/30 points (86.7%) and above for normal cognition. For statistical significance, an alpha level of 0.05 was used. Results: In total, 192 patients completed the MOCA: 104 with cardiac etiology, 35 with respiratory, 4 with trauma, and 49 with other. Median age for all patients was 59.3 years, and 58% were male. Mean (SE) MOCA score for all patients was 72.8 (1.1) percent. When MOCA score was converted to a binomial indicator of normal cognition, respiratory, traumatic, and other etiologies were more likely to exhibit impairment than cardiac etiology arrest when age, sex, witnessed status, length of ICU stay and coma were controlled for (OR: 2.52, 3.43, 2.18 respectively). These findings were nullified when time from arrest to MOCA administration was included. Of the MOCA subcategories, delayed recall was the most severely impacted, with patients recalling an average of 1.67 of 5 words after 5 minutes. Additionally, respiratory arrests performed significantly worse than cardiac etiology arrests in attention (4.1 vs 4.9 points, p=0.004) and language domains (1.9 vs. 2.3, p=0.04). Conclusions: Respiratory, traumatic, and other etiologies were more likely to exhibit abnormal cognition on the MOCA than those with a cardiac etiology. The etiological findings were nullified when time to cognitive examination was controlled for. Timing appears to influence cognitive assessments more than etiology.

Depression predicts long-term cognitive impairment in survivors of critical illness.

Intensive care unit (ICU) survivorship is associated with long-term cognitive impairment (LTCI). Our work has found post-ICU depression in up to 30% and posttraumatic stress disorder (PTSD) in up to 10% of ICU survivors. We hypothesized that post-ICU depression and PTSD are independently associated with LTCI in ICU survivors. This is a five-center nested prospective cohort of critically ill patients admitted to medical and surgical ICUs who underwent neuropsychological assessments at 3 and 12 months posthospital discharge. Our primary outcome was global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making Test, Part B, a test of executive functioning, at 3- and 12-month follow-up. Our independent variables were Beck Depression Inventory II and the PTSD Checklist-Specific Version measured at 3 and 12 months. We performed multivariable linear regression models controlling for covariates such as age, years of education, preexisting cognitive impairment, comorbidities, ventilator days, hypoxemia episodes, and days of delirium or coma. Of 1,047 patients in the combined cohort, 679 were alive and available for follow-up at 3 months. A total of 590 (87%) ICU survivors completed at least one 3-month assessment, and of the 554 who survived to 12 months, 519 (94%) completed both a 3- and 12-month assessment with a median age of 61 years (52-70 years) and mean daily Sequential Organ Failure Assessment score of 6 (4-8), 520 (88%) were mechanically ventilated, and 420 (71%) were with delirium. Of these, 113 (19%) had PTSD and 187 (32%) had depression at 3 months with similar rates at 12 months. Depression at 3 months was associated with lower 3-month RBANS (coefficient, -2.25; -3.10 to -1.39) and lower Trails B scores at both 3 months (odds ratio, 0.69; 0.56-0.85) and 12 months (odds ratio, 0.66; 0.52-0.84). Posttraumatic stress disorder at 3 months had no association with RBANS or Trails B scores at 3 or 12 months. Early post-ICU depression, but not PTSD, is independently associated with coexisting LTCI, even when controlling for past ICU delirium. Treatment for early depression represents a novel intervention area for LTCI prevention in ICU survivors. Prognostic/epidemiological, level III.