RESUMO
OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).
Assuntos
Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Ressecção Transuretral da Próstata/efeitos adversos , Proteômica , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/sangue , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/metabolismo , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/sangue , Período Perioperatório , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Biologia ComputacionalRESUMO
BACKGROUND & OBJECTIVES: Currently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta-analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups. METHOD: A systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I2, followed by subgroup analysis and meta-regression tests. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: In total, 16 studies were included in the present meta-analysis. Subjects with neurocognitive (n = 1444) and neuropsychiatric (n = 444) disorders had lower sRAGE levels in case-control (WMD: -0.21, 95% CI: -0.33, -0.10; p <.001) and cross-sectional (WMD: -0.29, 95% CI = -0.44, -0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: -0.87, 95% CI: -1.61, -0.13, p =.000), and age >50 years (WMD: -0.39, 95% CI: -0.74, -0.05, p =.000), had lower sRAGE levels in case-control studies. Also, dementia patients (WMD: -0.41, 95% CI: -0.72, -0.10, p =.014) with age >50 years (WMD: -0.33, 95% CI: -0.54, -0.13, p = 0.000) and in Asian countries (WMD: -0.28, 95% CI: -0.42, -0.13, p =.141) had lower sRAGE levels in cross-sectional studies. CONCLUSION: This meta-analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.
Assuntos
Biomarcadores , Transtornos Mentais , Transtornos Neurocognitivos , Receptor para Produtos Finais de Glicação Avançada , Humanos , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Disfunção Cognitiva/metabolismo , Produtos Finais de Glicação Avançada , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Transtornos Mentais/metabolismo , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/metabolismo , Receptor para Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
BACKGROUND: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. METHODS: Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). RESULTS: Of 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). CONCLUSIONS: We did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.
Assuntos
Adiponectina , Leptina , Receptores para Leptina , Humanos , Adiponectina/sangue , Masculino , Feminino , Idoso , Receptores para Leptina/sangue , Leptina/sangue , Estudos Prospectivos , Biomarcadores/sangue , Complicações Cognitivas Pós-Operatórias/sangue , Complicações Cognitivas Pós-Operatórias/epidemiologia , Fatores de Risco , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Período Perioperatório , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/etiologia , Idoso de 80 Anos ou maisRESUMO
The validity of dementia diagnostic criteria depends on their ability to distinguish dementia symptoms from pre-existing cognitive impairments. The study aimed to assess inter-rater reliability and concurrent validity of DSM-5 criteria for neurocognitive disorder in Down syndrome. The utility of mild neurocognitive disorder as a distinct diagnostic category, and the association between clinical symptoms and neurodegenerative changes represented by the plasma biomarker neurofilament light were also examined. 165 adults with Down syndrome were included. Two clinicians independently applied clinical judgement, DSM-IV, ICD-10 and DSM-5 criteria for dementia (or neurocognitive disorder) to each case. Inter-rater reliability and concurrent validity were analysed using the kappa statistic. Plasma neurofilament light concentrations were measured for 55 participants as a marker of neurodegeneration and between group comparisons calculated. All diagnostic criteria showed good inter-rater reliability apart from mild neurocognitive disorder which was moderate (k = 0.494). DSM- 5 criteria had substantial concurrence with clinical judgement (k = 0.855). When compared to the no neurocognitive disorder group, average neurofilament light concentrations were higher in both the mild and major neurocognitive disorder groups. DSM-5 neurocognitive disorder criteria can be used reliably in a Down syndrome population and has higher concurrence with clinical judgement than the older DSM-IV and ICD-10 criteria. Whilst the inter-rater reliability of the mild neurocognitive disorder criteria was modest, it does appear to identify people in an early stage of dementia with underlying neurodegenerative changes, represented by higher average NfL levels.
Assuntos
Síndrome de Down , Filamentos Intermediários/metabolismo , Transtornos Neurocognitivos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Síndrome de Down/sangue , Síndrome de Down/diagnóstico , Feminino , Humanos , Masculino , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/diagnósticoRESUMO
BACKGROUND: Schizophrenia (SCZ) and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased high mobility group protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-related protein (DKK1), a Wnt/ß-catenin signaling antagonist, affect the blood-brain barrier and induce neurotoxic effects and neurocognitive deficits. AIM: The present study aims to examine HMGB1 and DDK1 in nonresponders to treatments (NRTT) with antipsychotics (n = 60), partial RTT (PRTT, n = 55), and healthy controls (n = 43) in relation to established markers of SCZ, including interleukin (IL)-6, IL-10, and CCL11 (eotaxin), and to delineate whether these proteins are associated with the SCZ symptom subdomains and neurocognitive impairments. RESULTS: HMGB1, DKK1, IL-6, and CCL11 were significantly higher in SCZ patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls, while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that SCZ was best predicted by increased DDK1 and HMGB1, while NRTT (vs PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism, and negative (PHEMN) symptoms and formal thought disorders was explained by HMGB1, IL-6, and CCL11, while most neurocognitive functions were predicted by HMGB1, DDK1, and CCL11. CONCLUSIONS: The neurotoxic effects of HMGB1, DKK1, IL-6, and CCL11 including the effects on the blood-brain barrier and the Wnt/ß-catenin signaling pathway may cause impairments in executive functions and working, episodic, and semantic memory and explain, in part, PHEMN symptoms and a nonresponse to treatment with antipsychotic drugs.
Assuntos
Antipsicóticos/farmacologia , Quimiocina CCL11/sangue , Função Executiva , Proteína HMGB1/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Interleucina-6/sangue , Transtornos da Memória , Transtornos Neurocognitivos , Esquizofrenia , Adolescente , Adulto , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Transtornos da Memória/sangue , Transtornos da Memória/imunologia , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/imunologia , Transtornos Neurocognitivos/fisiopatologia , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Esquizofrenia/imunologia , Adulto JovemRESUMO
BACKGROUND: Surgical interventions result in a postoperative rise in circulating inflammatory cytokines and high molecular group box protein 1 (HMGB1). Herein, the impact of a sedentary lifestyle and other age-related factors on the development of perioperative neurocognitive disorders (PND) following non-cardiac surgical procedures was assessed in an older (55-75 years-old) surgical population. METHODS: Prior to surgery, patients were asked questions regarding their sedentary behavior and daily habits. They also passed the Mini Mental State Examination (MMSE) and their blood circulating interleukin 6 (IL-6) and HMGB1 levels were assayed by ELISA. IL-6 and HMGB1 measurements were repeated respectively 6 and 24 h after surgery. MMSE was re-evaluated 6 weeks and whenever possible 3 months after surgery. RESULTS: Thirty-eight patients were enrolled in the study from January until July 2019. The study identified self-sufficiency, multilinguism, and overall health score on the geriatric depression scale, as protectors against PND. No other demographic (age, sex), environmental (solitary/non-solitary housing, professional and physical activities, smoking, alcohol drinking), comorbidity (antipsychotic drug uptake, diabetic state) and type of surgery (orthopedic, general, genitourinary) influenced the development of PND. Although some factors (surgery type and age) influenced the surgery-induced rise in the circulating IL-6 levels, they did not impact HMGB1. CONCLUSION: Inflammaging, reflected by the greater increment of surgery-induced IL-6 in patients with advanced age, was present. As trauma-induced release of HMGB1 was not similarly affected by age, we surmise that HMGB1, rather than circulating cytokines, is the key driver of the trauma-induced inflammatory cascade leading to PND. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03805685 .
Assuntos
Inflamação/sangue , Inflamação/epidemiologia , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/epidemiologia , Período Pré-Operatório , Comportamento Sedentário , Idoso , Bélgica/epidemiologia , Estudos de Coortes , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O2 and expired CO2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O2 and CO2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. METHODS: We examine the effects of controlled alterations in both ET O2 and CO2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2 and O2 in various combinations commonly observed during anesthesia. RESULTS: Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. CONCLUSIONS: Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. TRIAL REGISTRATION: ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.
Assuntos
Dióxido de Carbono/análise , Imageamento por Ressonância Magnética/métodos , Transtornos Neurocognitivos/etiologia , Oxigênio/análise , Adulto , Gasometria/métodos , Dióxido de Carbono/sangue , Feminino , Humanos , Hiperóxia/fisiopatologia , Hipocapnia/fisiopatologia , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/fisiopatologia , Oxigênio/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/fisiopatologiaRESUMO
Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease-modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16-17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSß+ thalassaemia; n = 52 HbSS/HbSß0 thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSß+ thalassaemia; n = 8 HbSS/HbSß0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSß thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSß0 thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSß0 thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSß+ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSß+ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSß0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.
Assuntos
Anemia Falciforme , Atenção/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Transtornos Neurocognitivos/induzido quimicamente , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Hemoglobina Fetal/metabolismo , Humanos , Hidroxiureia , Contagem de Leucócitos , Masculino , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/fisiopatologiaRESUMO
Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in a cross-sectional study that enrolled schizophrenia patients with (n = 40) and without (n = 40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial least squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), which lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA, and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.
Assuntos
Arildialquilfosfatase/fisiologia , Imunoglobulina M/imunologia , Malondialdeído/sangue , Transtornos Neurocognitivos/etiologia , Neuroimunomodulação/fisiologia , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Antipsicóticos/uso terapêutico , Arildialquilfosfatase/imunologia , Índice de Massa Corporal , Feminino , Humanos , Imunidade Inata , Interleucina-4/sangue , Interleucina-6/sangue , Análise dos Mínimos Quadrados , Modelos Logísticos , Masculino , Malondialdeído/imunologia , Pessoa de Meia-Idade , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/imunologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/imunologia , Índice de Gravidade de Doença , Fatores Socioeconômicos , Fator de Necrose Tumoral alfa/fisiologia , Adulto JovemRESUMO
BACKGROUND: Neurocognitive dysfunction remains prevalent among people living with HIV (PLWH), even after viral suppression on combination antiretroviral therapy (cART). We investigated associations between neuropsychological performance (NP) and patterns of circulating exosomal microRNA (exo-miRNA) expression in PLWH on cART. SETTING: A cross-sectional examination of plasma exo-miRNA among PLWH on cART with systemic viral suppression and volunteers without HIV infection. METHODS: Thirty-one PLWH who started cART during early infection (n = 19) or chronic infection (n = 12) participated in phlebotomy and an 11-test neuropsychological battery after >1 year on treatment. NP higher- or lower-performing participants were categorized based on normalized neuropsychological scores. Total RNA was extracted from purified exosomes of 31 PLWH and 5 volunteers without HIV and subject to small RNA sequencing. Differential expression of exo-miRNAs was examined and biological functions were predicted. RESULTS: Eleven exo-miRNAs were up-regulated in NP lower-performing (n = 18) relative to higher-performing PLWH (n = 13). A high proportion of the differentiating exo-miRNA target the axon guidance KEGG pathway and neurotrophin tyrosine receptor kinase signaling Gene Ontology pathway. Differential expression analysis of exo-miRNAs between NP lower- (n = 7) and higher-performing (n = 12) PLWH within the early infection group alone confirmed largely consistent findings. CONCLUSIONS: Plasma exo-miRNA content differed between NP higher- and lower-performing PLWH. Several differentially expressed exo-miRNAs were predicted to be involved in inflammation and neurodegeneration pathways. Exo-miRNA in plasma may indicate cross-talk between the circulation and central nervous system and thus may be clinically relevant for neurocognitive dysfunction in PLWH.
Assuntos
Exossomos/metabolismo , Infecções por HIV/sangue , Infecções por HIV/psicologia , MicroRNAs/sangue , Transtornos Neurocognitivos/sangue , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Quimioterapia Combinada , Exossomos/genética , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transtornos Neurocognitivos/virologia , Testes Neuropsicológicos , Transdução de Sinais/genéticaRESUMO
OBJECTIVES: Premenstrual worsening has been often complained by patients with multiple sclerosis (MS). However, there is no quantitative study in the literature regarding premenstrual worsening and there are only a few studies for its reasons. In diseases such as MS, which there are limited evidence about the etiology and the triggers, detection of the variables in menstrual period, which is defined relatively easy, has a great potential to shed light to the disease. In the present study, we aimed to detect whether there was a deterioration in premenstrual period of patients with MS and to measure the observed deterioration and the relationships between demographics, physical and hormonal variables. PATIENTS AND METHODS: This study included 44 patients with MS, who were diagnosed according to McDonald criteria, and 14 healthy controls. For two consecutive cycles, cases were evaluated on the basis of neurological functions in the premenstrual and ovulation phases. In each examination, blood samples were obtained for detection of the levels of sex hormones (FSH, LH, E2, Progesterone). In the first and the fourth examinations, we applied Multiple Sclerosis Functional Composite (MSFC). RESULTS: Patients with MS showed poor performance in all used measurements than the healthy controls. Premenstrual period was worse based on cognitive aspects than the ovulation period in both MS patients and healthy controls. This was more evident in patients with MS. Patients treated with immunomodulatory agents had better cognitive performance than those were not given these agents. CONCLUSION: In our study, the patients with MS were found to be worse in cognition, and physical performance when compared with the healthy group. In premenstrual period, cognitive functions, and physical performance deteriorated in patients with MS. Healthy people seemed to be deteriorated on cognition measured with Paced Auditory Serial Addition Test.
Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ciclo Menstrual/sangue , Esclerose Múltipla/sangue , Transtornos Neurocognitivos/sangue , Progesterona/sangue , Adulto , Cognição/fisiologia , Feminino , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/psicologia , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/psicologia , Distribuição Aleatória , Adulto JovemRESUMO
Background Higher serum uric acid levels are associated with cardiovascular and neurovascular disease, but whether these relationships are causal is not known. We applied Mendelian randomization approaches to assess the association between genetically determined uric acid levels and outcomes under study in large clinical trials. Methods and Results We used 28 genetic variants related to serum uric acid as instruments to perform a range of 2-sample Mendelian randomization methods. Our analysis had statistical power to detect clinically relevant effects of genetically determined serum uric acid levels on the considered clinical outcomes; cognitive function, Alzheimer disease, coronary heart disease, myocardial infarction, systolic blood pressure, and stroke. There was some suggestive evidence for an association between higher genetically determined serum uric acid and cognitive function. There was also some suggestive evidence of a relationship between coronary heart disease, systolic blood pressure, and the serum uric acid genetic instruments, but likely related to genetic pleiotropy. Overall, there was no consistent evidence of a clinically relevant effect of genetically determined serum uric acid on any of the considered outcomes. Conclusions This Mendelian randomization study does not support a clinically relevant causal effect of genetically determined serum urate on a range of cardiovascular and neurovascular outcomes. The weak association of genetically determined serum urate with coronary heart disease and systolic blood pressure may be because of pleiotropic effects. If urate lowering drugs such as allopurinol are found to affect these outcomes in clinical trials, then the effects may be mediated through urate independent mechanisms.
Assuntos
Doenças Cardiovasculares/genética , Transtornos Cerebrovasculares/genética , Hiperuricemia/genética , Transtornos Neurocognitivos/genética , Polimorfismo de Nucleotídeo Único , Ácido Úrico/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/psicologia , Cognição , Estudo de Associação Genômica Ampla , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Análise da Randomização Mendeliana , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.
Assuntos
Proteína C-Reativa/análise , Delírio/etiologia , Inflamação/complicações , Transtornos Neurocognitivos/etiologia , Complicações Pós-Operatórias/etiologia , Idoso , Delírio/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Transtornos Neurocognitivos/sangue , Complicações Pós-Operatórias/sangue , RiscoRESUMO
INTRODUCTION: HIV Associated Neurocognitive Disorder (HAND) is still prevalent even in the ART (Anti-Retroviral Therapy) era. It may have some association with CD4 counts and Anti-Retroviral Therapy. The prevalence of HAND in HIV-patients, was, therefore studied in the context of ART and CD4 counts. METHODS: Modified Mini Mental State Examination scores of 200 (65% males) HIV-positive patients and 200 controls were analyzed in the context of ART and CD4 counts. RESULTS: Maximum number of participants were educated between 8th-12th class (89.5%), aged between 25-50 years (81.5%) and a higher proportion of males had a CD4 count <500 (69.2%) (p=0.007). Using 3MS, 21% patients (mean 76.24±1.51) and none of the controls were found to be neurocognitively impaired. Mean scores of patients with CD4 counts<500(82.54±5.58) were lesser in comparison to those of patients with CD4 counts>500 (p<0.001). Those with an ART duration of <48 months had a lower score in comparison to those with an ART duration of >72 months (p=0.005).Most decrease from maximum value was seen in similarities (48.3 %), second recall (36.1 %), repetition (33.4 %), copying two pentagons (28.3 %), read and obey (24.0 %), mental reversal (22.7 %) and first recall (21.3%) parameters of Modified Mini Mental State Examination. CONCLUSIONS: HAND was less prevalent in the present study in comparison to past literature. CD4 counts and ART duration had an inverse association with the degree of cognitive impairment. The parameters of Modified Mini Mental State Examination showing maximum impairment may be compiled to form a short screening questionnaire.
Assuntos
Infecções por HIV/epidemiologia , Transtornos Neurocognitivos/epidemiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/sangue , Infecções por HIV/terapia , Humanos , Índia/epidemiologia , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/tratamento farmacológico , PrevalênciaRESUMO
This study aimed to evaluate the association of the metabolic syndrome (MS) and its components with neurocognition among patients with schizophrenia. 121 patients with schizophrenia from an outpatient service of two psychiatric centers were assessed on a neurocognitive battery and by metabolic measures. More than half (56.2%) of the patients fulfilled the consensus criteria for MS. After controlling/adjusting for various covariates (age, education in years, duration of illness, age of onset, Positive and Negative Symptom scale score and presence of smoking status), it was found that compared to patients without MS, those with MS had significantly poorer performance "in the cognitive domains" of cognitive processing and selective attention (Stroop effect percentile; p value 0.002; effect size-0.45) and auditory and verbal memory (AVLT; p value <0.001; effect size 0.68). Patients with a higher number of abnormal parameters of MS had poorer functioning in the domains of cognitive processing and selective attention, auditory and verbal memory, and executive tasks. To conclude, this two center study suggests that MS has a negative impact on neurocognition in patients with schizophrenia. There is a need to identify and monitor metabolic abnormalities among patients with schizophrenia to minimize the negative effect of metabolic parameters on neurocognition.
Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/psicologia , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/psicologia , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adulto , Atenção/fisiologia , Estudos Transversais , Feminino , Humanos , Masculino , Memória/fisiologia , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Transtornos Neurocognitivos/diagnóstico , Testes Neuropsicológicos , Esquizofrenia/diagnóstico , Adulto JovemRESUMO
Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in IgM-mediated autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative-specific epitopes (OSEs), nitroso (NO), and nitro (NO2) adducts in schizophrenia remain unknown. This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl, and NO2-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls. Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO2-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2-42.2%) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO2-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall. These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in natural IgM attenuate CIRS functions and that this impairment may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.
Assuntos
Autoanticorpos/sangue , Ácidos Dicarboxílicos/sangue , Imunoglobulina M/sangue , Malondialdeído/sangue , Transtornos Neurocognitivos/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/epidemiologia , Valor Preditivo dos Testes , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Método Simples-CegoRESUMO
Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.
Assuntos
Ceruloplasmina/líquido cefalorraquidiano , Infecções por HIV/sangue , Infecções por HIV/complicações , Haptoglobinas/metabolismo , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/virologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Terapia Antirretroviral de Alta Atividade , Biomarcadores/líquido cefalorraquidiano , Comorbidade , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Inflamação/líquido cefalorraquidiano , Ferro/metabolismo , Masculino , Análise Multivariada , Transtornos Neurocognitivos/complicações , Análise de RegressãoRESUMO
Biomarkers are very useful in the diagnosis and identification of neurocognitive impairments (NCIs) or disorders (NCDs) in HIV-infected individuals, and in particular, blood biomarkers have become more promising because they are cheap and easy to obtain or accept. A systematically literature retrieval was conducted by using PubMed, CNKI, Wanfang and VIP databases for studies about blood biomarkers of neurocognitive impairment of HIV-infected individuals in 2008-2017, according to the inclusion and exclusion criteria. Finally, a total of 43 related articles were included for this systematic review for the purpose of providing scientific evidence for further research and clinical practices.
Assuntos
Biomarcadores/sangue , Transtornos Cognitivos/sangue , Infecções por HIV/complicações , Adulto , Antirretrovirais/uso terapêutico , Transtornos Cognitivos/diagnóstico , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/diagnósticoRESUMO
A 14-year-old boy presented to our institution with a 1-month history of neurocognitive decline and intermittent fevers. His history was significant for fevers, headaches, and a 10-lb weight loss. Previous examinations by multiple medical providers were significant only for bilateral cervical lymphadenopathy. Previous laboratory workup revealed leukopenia, neutropenia, and elevated inflammatory markers. Despite improvement in his laboratory values after his initial presentation, his fevers persisted, and he developed slowed and "jerky" movements, increased sleep, slurred speech, delusions, visual hallucinations, and deterioration in his school performance. A brain MRI performed at an outside hospital before admission at our institution was concerning for patchy, increased T2 and fluid-attenuated inversion recovery signal intensity in multiple areas, including the basal ganglia. After transfer to our institution and admission to the pediatric hospital medicine team, the patient had an acute decompensation. Our subspecialists will discuss the initial evaluation, workup, differential diagnosis, definitive diagnosis, and subsequent management of this patient.
Assuntos
Febre/diagnóstico por imagem , Leucopenia/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Transtornos Neurocognitivos/diagnóstico por imagem , Neutropenia/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Febre/sangue , Febre/psicologia , Humanos , Leucopenia/sangue , Leucopenia/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/psicologia , Neutropenia/sangue , Neutropenia/psicologiaRESUMO
Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Naâº: p < 0.001; Kâº: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r² = 0.0046, p = 0.77), ESS (r² = 0.0052, p = 0.54) and MNA (r² = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65â»75 years, p = 0.001; 76â»85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.