Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson / Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases

Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. [...] (AU)

Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases. (AU)

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. / Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

A comparative cross-cultural study of the prevalence of late life depression in low and middle income countries.

BACKGROUND: Current estimates of the prevalence of depression in later life mostly arise from studies carried out in Europe, North America and Asia. In this study we aimed to measure the prevalence of depression using a standardised method in a number of low and middle income countries (LMIC). METHODS: A one-phase cross-sectional survey involving over 17,000 participants aged 65 years and over living in urban and rural catchment areas in 13 sites from 9 countries (Cuba, Dominican Republic, Puerto Rico, Mexico, Venezuela, Peru, China, India and Nigeria). Depression was assessed and compared using ICD-10 and EURO-D criteria. RESULTS: Depression prevalence varied across sites according to diagnostic criteria. The lowest prevalence was observed for ICD-10 depressive episode (0.3 to 13.8%). When using the EURO-D depression scale, the prevalence was higher and ranged from 1.0% to 38.6%. The crude prevalence was particularly high in the Dominican Republic and in rural India. ICD-10 depression was also associated with increased age and being female. LIMITATIONS: Generalisability of findings outside of catchment areas is difficult to assess. CONCLUSIONS: Late life depression is burdensome, and common in LMIC. However its prevalence varies from culture to culture; its diagnosis poses a significant challenge and requires proper recognition of its expression.

Monoclonal antibody against Saint Louis encephalitis prM viral protein.

Saint Louis encephalitis virus belongs to Flavivirus genus; Flaviviridae family jointly with other medically important flaviviruses including dengue virus and West Nile virus. The biological properties and functions of prM flavivirus protein are under investigation due to its importance in the generation of infectious virion and host interactions. Monoclonal antibodies have become powerful tools in this approach. Also the use of monoclonal antibodies has been successfully applied for antigenic analysis, clinical diagnosis and treatments. Here, using an immunofluorescence assay we describe a monoclonal antibody (mAb 3D2) that uniquely recognizes native prM Saint Louis encephalitis virus protein expressed in either C6/36-HT or Vero cells. In conclusion, mAb3D2 has significant potential for use in (a) the diagnosis of infections caused by this virus and (b) therapeutic use to treat patients infected by this virus and fundamental research to understand the role of the prM in the Saint Louis encephalitis virus infectious process.

A brief dementia screener suitable for use by non-specialists in resource poor settings--the cross-cultural derivation and validation of the brief Community Screening Instrument for Dementia.

OBJECTIVE: Brief screening tools for dementia for use by non-specialists in primary care have yet to be validated in non-western settings where cultural factors and limited education may complicate the task. We aimed to derive a brief version of cognitive and informant scales from the Community Screening Instrument for Dementia (CSI-D) and to carry out initial assessments of their likely validity. METHODS: We applied Mokken analysis to CSI-D cognitive and informant scale data from 15 022 participants in representative population-based surveys in Latin America, India and China, to identify a subset of items from each that conformed optimally to item response theory scaling principles. The validity coefficients of the resulting brief scales (area under ROC curve, optimal cutpoint, sensitivity, specificity and Youden's index) were estimated from data collected in a previous cross-cultural validation of the full CSI-D. RESULTS: Seven cognitive items (Loevinger H coefficient 0.64) and six informant items (Loevinger H coefficient 0.69) were selected with excellent hierarchical scaling properties. For the brief cognitive scale, AUROC varied between 0.88 and 0.97, for the brief informant scale between 0.92 and 1.00, and for the combined algorithm between 0.94 and 1.00. Optimal cutpoints did not vary between regions. Youden's index for the combined algorithm varied between 0.78 and 1.00 by region. CONCLUSION: A brief version of the full CSI-D appears to share the favourable culture- and education-fair screening properties of the full assessment, despite considerable abbreviation. The feasibility and validity of the brief version still needs to be established in routine primary care.

Clinical presentation of anxiety among patients with epilepsy.

Different factors have been related with interictal anxiety, reported in 10%-25% of patients with epilepsy. We determined the frequency of interictal anxiety in 196 patients with active epilepsy in a cross-sectional survey to know which symptoms of anxiety were most frequently reported in patients with epilepsy and to analyze the factors associated with their presence. Patients were assessed with the Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS), and the Hamilton Anxiety Scale (HAMA). Data were analyzed with a logistic regression model. The HAMA ratings revealed that 38.8% experienced significant anxiety symptoms, as defined by a rating above 18 points. Use of primidone, depression, cryptogenic, and posttraumatic etiologies significantly predicted anxiety after logistic regression. Symptoms related to higher scores on HAMA were anxious mood, tension, insomnia, intellectual function, depressed mood, cardiovascular and genitourinary symptoms. Further studies should be performed to define the role of psychosocial factors in the development and evolution of anxiety among these patients.

Is dementia reversible in patients with neurocysticercosis?

OBJECTIVE: To determine the correlates and outcome of dementia in patients with neurocysticercosis (NCC). METHODS: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. RESULTS: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. CONCLUSIONS: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.

Primidone is associated with interictal depression in patients with epilepsy.

Depressive symptoms are common in epilepsy. To determine associations between depression and demographic, clinical, and pharmacological factors among epileptic patients, we conducted a cross-sectional survey. We evaluated 241 epileptic outpatients at a neurological center in a 6-month period. Depressive syndrome was diagnosed when both the Montgomery-Asberg Scale and the Beck Depression Inventory were rated above the standard cutoff points. Bivariate and multivariate analyses were performed to assess the differences between depressed and nondepressed patients with respect to demographic, clinical, and pharmacological features. Depressive syndrome was diagnosed in 42.7% of patients (n=103). Factors associated in the bivariate analysis were: cryptogenic etiology, posttraumatic epilepsy, use of primidone, and inadequate seizure control. After logistic regression, inadequate seizure control (OR 3.08, 95% CI 1.40-6.77, P=0.005) and use of primidone (OR 4.08, 95% CI 2.09-7.98; P<0.001) remained significantly associated. Depression was common and associated with inadequate seizure control and use of primidone.

Effects of the novel antidepressant S-adenosyl-methionine on alpha 1- and beta-adrenoceptors in rat brain.

alpha 1- and beta-adrenoceptors were studied ex vivo in the brains of rats receiving repeated daily treatment with the standard antidepressant imipramine or the atypical antidepressant S-adenosyl-L-methionine (SAM), which has minimal effects on monoamine reuptake or turnover. Consistent with past studies, a decrease in the density of beta receptors at three weeks and an increase in the affinity of alpha 1 receptors for the agonist phenylephrine at one week of treatment was observed with imipramine. By comparison, an increase in the density of beta receptors and a decrease in the affinity of alpha 1 receptors for phenylephrine was observed at one week of treatment with SAM. These changes were no longer apparent at three weeks of treatment. The results suggest that treatment with SAM does lead to changes in adrenergic neurotransmission, but that down regulation of beta receptors or increased agonist affinity of alpha 1 receptors may not be necessary for the production of antidepressant effects.