Evaluating SVM and MLDA in the extraction of discriminant regions for mental state prediction

Pattern recognition methods have been successfully applied in several functional neuroimaging studies. These methods can be used to infer cognitive states, so-called brain decoding. Using such approaches, it is possible to predict the mental state of a subject or a stimulus class by analyzing the spatial distribution of neural responses. In addition it is possible to identify the regions of the brain containing the information that underlies the classification. The Support Vector Machine (SVM) is one of the most popular methods used to carry out this type of analysis. The aim of the current study is the evaluation of SVM and Maximum uncertainty Linear Discrimination Analysis (MLDA) in extracting the voxels containing discriminative information for the prediction of mental states. The comparison has been carried out using fMRI data from 41 healthy control subjects who participated in two experiments, one involving visual-auditory stimulation and the other based on bimanual fingertapping sequences. The results suggest that MLDA uses significantly more voxels containing discriminative information (related to different experimental conditions) to classify the data. On the other hand, SVM is more parsimonious and uses less voxels to achieve similar classification accuracies. In conclusion, MLDA is mostly focused on extracting all discriminative information available, while SVM extracts the information which is sufficient for classification. (C) 2009 Elsevier Inc. All rights reserved.

Common mental disorders during pregnancy and adverse obstetric outcomes

Methods. A prospective cohort study was conducted with 831 pregnant women from antenatal clinics in primary healthcare in Sao Paulo, Brazil. The clinical interview schedule-revised and demographic questionnaires were administered between the 20th and 30th weeks of gestation. Information on infant weight and gestational age at birth were obtained from hospital records. Univariate analyses were used to examine the association between the main exposure and main outcomes. Statistical associations were examined with chi

Optimizing the CAMCOG test in the screening for mild cognitive impairment and incipient dementia: saving time with relevant domains

Objective: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer`s disease (AD) in clinical practice. Methods: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. Results: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC = 0.80 +/- 0.03 for the reduced CAMCOG; AUC = 0.79 +/- 0.03 for the original CAMCOG). Conclusion: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice. Copyright (C) 2010 John Wiley & Sons, Ltd.

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Psychometric characteristics of the Rivermead Behavioural Memory Test (RBMT) as an early detection instrument for dementia and mild cognitive impairment in Brazil

Background: The Rivermead Behavioural Memory Test (RBMT) assesses everyday memory by means of tasks which mimic daily challenges. The objective was to examine the validity of the Brazilian version of the RBMT to detect cognitive decline. Methods: 195 older adults were diagnosed as normal controls (NC) or with mild cognitive impairment (MCI) or Alzheimer`s disease (AD) by a multidisciplinary team, after participants completed clinical and neuropsychological protocols. Results: Cronbach`s alpha was high for the total sample for the RBMT profile (PS) and screening scores (SS) (PS=0.91, SS=0.87) and for the AD group (PS=0.84, SS=0.85), and moderate for the MCI (PS=0.62, SS=0.55)and NC (PS=0.62, SS=0.60) groups. RBMT total scores, Appointment, Pictures, Immediate and Delayed Story, Immediate and Delayed Route, Delayed Message and Date contributed to differentiate NC from MCI. ROC curve analyses indicated high accuracy to differentiate NC from AD patients, and, moderate accuracy to differentiate NC from MCI. Conclusions: The Brazilian version of the RBMT seems to be an appropriate instrument to identify memory decline in Brazilian older adults.

Higher Serum sTNFR1 Level Predicts Conversion from Mild Cognitive Impairment to Alzheimer`s Disease

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer`s disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor alpha (TNF-alpha) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-alpha and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-alpha, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 +/- 10.0 months. At baseline, there were no statistically significant differences in serum TNF-alpha, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-alpha and sTNFR2. Abnormal activation of TNF-alpha signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.

Limitations of the Mini-Mental State Examination for screening dementia in a community with low socioeconomic status

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of cognitive impairment worldwide, but its ability to produce valid estimates of dementia in populations of low socioeconomic status and minimal literacy skills has not been adequately established. The authors investigated the psychometric properties of the MMSE in a community-based sample of older Brazilians. Cross-sectional one-phase population-based study of all residents of pre-defined areas of the city of Sao Paulo, aged 65 years or over. The Brazilian version of the MMSE was compared with DSM-IV diagnosis of dementia assessed with a harmonized one-phase procedure developed by the 10/66 Dementia Research Group. Analyses were performed with 1,933 participants of the SPAH study. Receiver operating characteristic analysis showed that the MMSE cut-point of 14/15 was associated with 78.7% sensitivity and 77.8% specificity for the diagnosis of dementia amongst participants with no formal education, and the cut-point 17/18 with 91.9% sensitivity and 89.5% specificity for those with at least 1 year of formal education (areas under the curves 0.87 and 0.94, respectively; P = 0.03). Even with these best fitting cut-points, the MMSE estimate of the prevalence of dementia was four times higher than determined by the DSM-IV criteria. Education, age, sex and income influenced MMSE scores, independently of dementia caseness. The MMSE is an adequate tool for screening dementia in older adults with minimum literacy skills, but misclassification is unacceptably high for older adults who are illiterate, which has serious consequences for research and clinical practice in low and middle income countries, where the proportion of illiteracy among older adults is high.

Cognitive training increases platelet PLA(2) activity in healthy elderly subjects

Phospholipases A(2) (PLA(2)) are ubiquitous enzymes involved in membrane fatty acid metabolism and intracellular signalling. Recent studies have shown that PLA(2) subtypes are implicated in the modulation of pathways related to memory acquisition and retrieval. We investigated the effects of cognitive training on platelet PLA(2) activity in healthy elderly individuals. Twenty-three cognitively unimpaired older adults were randomly assigned to receive memory training or standard outpatient care only. Both groups were cognitively assessed by the same protocol, and the experimental group (EG) underwent a four-session memory training intervention. Pre- and post-test measures included prose and list recall, WAIS-III digit symbol, strategy use measures and platelet PLA(2) group activity. After cognitive training, patients in the EG group had significant increase in cytosolic, calcium-dependent PLA(2) (cPLA(2)), extracellular (or secreted), calcium-dependent PLA(2) (sPLA(2)), total platelet PLA(2) activity, and significant decrease in platelet calcium-independent PLA(2) (iPLA(2)) activity. Our results suggest that memory training may have a modulating effect in PLA(2)-mediated biological systems associated with cognitive functions and neurodegenerative diseases. (c) 2008 Elsevier Ltd. All rights reserved.

Can the CAMCOG be a good cognitive test for patients with Alzheimer`s disease with low levels of education?

Background: The Cambridge Cognitive Examination (CAMCOG) is a useful test in screening for Alzheimer`s disease (AD). However, the interpretation of CAMCOG cut-off scores is problematic and reference values are needed for different educational strata. Given the importance of earlier diagnoses of mild dementia, new cut-off values are required which take into account patients with low levels of education. This study aims to evaluate whether the CAMCOG can be used as an accurate screening test among AD patients and normal controls with different educational levels. Methods: Cross-sectional assessment was undertaken of 113 AD and 208 elderly controls with heterogeneous educational levels (group 1: 1-4 years; group 2: 5-8 years; and group 3: >= 9 years) from a geriatric clinic. submitted to a thorough diagnostic evaluation for AD including the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Controls had no cognitive or mood complaints. Sensitivity (SE) and specificity (SP) for the CAMCOG in each educational group was assessed with receiver-operator-characteristic (ROC) curves. Results: CAMCOG mean values were lower when education was reduced in both diagnostic groups (controls - group 1: 87; group 2: 91; group 3: 96; AD - group 1: 63; group 2: 62; group 3: 77). Cutoff scores for the three education groups were 79, 80 and 90, respectively. SE and SP varied among the groups (group 1: 88.1% and 83.5%; group 2: 84.6% and 96%; group 3: 70.8% and 90%). Conclusion: The CAMCOG can be used as a cognitive test for patients with low educational level with good accuracy. Patients with higher education showed lower scores than previously reported.

Development of Lifetime Comorbidity in the World Health Organization World Mental Health Surveys

Context: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. Objective: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. Design: Nationally or regionally representative community surveys. Setting: Fourteen countries. Participants: A total of 21 229 survey respondents. Main Outcome Measures: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. Results: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. Conclusions: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study.

Twelve-Month Prevalence of and Risk Factors for Suicide Attempts in the World Health Organization World Mental Health Surveys

Objective: Although suicide is a leading cause of death worldwide, clinicians and researchers lack a data-driven method to assess the risk of suicide attempts. This study reports the results of an analysis of a large cross-national epidemiologic survey database that estimates the 12-month prevalence of suicidal behaviors, identifies risk factors for suicide attempts, and combines these factors to create a risk index for 12-month suicide attempts separately for developed and developing countries. Method: Data come from the World Health Organization (WHO) World Mental Health (WMH) Surveys (conducted 2001-2007), in which 108,705 adults from 21 countries were interviewed using the WHO Composite International Diagnostic Interview. The survey assessed suicidal behaviors and potential risk factors across multiple domains, including socio-demographic characteristics, parent psychopathology, childhood adversities, DSM-IV disorders, and history of suicidal behavior. Results: Twelve-month prevalence estimates of suicide ideation, plans, and attempts are 2.0%, 0.6%, and 0.3%, respectively, for developed countries and 2.1%, 0.7%, and 0.4%, respectively, for developing countries. Risk factors for suicidal behaviors in both developed and developing countries include female sex, younger age, lower education and income, unmarried status, unemployment, parent psychopathology, childhood adversities, and presence of diverse 12-month DSM-IV mental disorders. Combining risk factors from multiple domains produced risk indices that accurately predicted 12-month suicide attempts in both developed and developing countries (area under the receiver operating characteristic curve = 0.74-0.80). Conclusions: Suicidal behaviors occur at similar rates in both developed and developing countries. Risk indices assessing multiple domains can predict suicide attempts with fairly good accuracy and may be useful in aiding clinicians in the prediction of these behaviors. J Clin Psychiatry 2010;71(12):1617-1628 (C) Copyright 2010 Physicians Postgraduate Press, Inc.

Differential expression of presynaptic genes in a rat model of postnatal hypoxia: relevance to schizophrenia

Obstetric complications play a role in the pathophysiology of schizophrenia. However, the biological consequences during neurodevelopment until adulthood are unknown. Microarrays have been used for expression profiling in four brain regions of a rat model of neonatal hypoxia as a common factor of obstetric complications. Animals were repeatedly exposed to chronic hypoxia from postnatal (PD) day 4 through day 8 and killed at the age of 150 days. Additional groups of rats were treated with clozapine from PD 120-150. Self-spotted chips containing 340 cDNAs related to the glutamate system (""glutamate chips"") were used. The data show differential (up and down) regulations of numerous genes in frontal (FR), temporal (TE) and parietal cortex (PAR), and in caudate putamen (CPU), but evidently many more genes are upregulated in frontal and temporal cortex, whereas in parietal cortex the majority of genes are downregulated. Because of their primary presynaptic occurrence, five differentially expressed genes (CPX1, NPY, NRXN1, SNAP-25, and STX1A) have been selected for comparisons with clozapine-treated animals by qRT-PCR. Complexin 1 is upregulated in FR and TE cortex but unchanged in PAR by hypoxic treatment. Clozapine downregulates it in FR but upregulates it in PAR cortex. Similarly, syntaxin 1A was upregulated in FR, but downregulated in TE and unchanged in PAR cortex, whereas clozapine downregulated it in FR but upregulated it in PAR cortex. Hence, hypoxia alters gene expression regionally specific, which is in agreement with reports on differentially expressed presynaptic genes in schizophrenia. Chronic clozapine treatment may contribute to normalize synaptic connectivity.

Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries

Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved.

Verbal fluency in the detection of mild cognitive impairment and Alzheimer`s disease among Brazilian Portuguese speakers: the influence of education

Background: Verbal fluency (VF) tasks are simple and efficient clinical tools to detect executive dysfunction and lexico-semantic impairment. VF tasks are widely used in patients with suspected dementia, but their accuracy for detection of mild cognitive impairment (MCI) is still under investigation. Schooling in particular may influence the subject`s performance. The aim of this study was to compare the accuracy of two semantic categories (animals and fruits) in discriminating controls, MCI patients and Alzheimer`s disease (AD) patients. Methods: 178 subjects, comprising 70 controls (CG), 70 MCI patients and 38 AD patients, were tested on two semantic VF tasks. The sample was divided into two schooling groups: those with 4-8 years of education and those with 9 or more years. Results: Both VF tasks - animal fluency (VFa) and fruits fluency (VFf) - adequately discriminated CG from AD in the total sample (AUC = 0.88 +/- 0.03, p < 0.0001) and in both education groups, and high educated MCI from AD (VFa: AUC = 0.82 +/- 0.05, p < 0.0001; VFf: AUC = 0.85 +/- 0.05, p < 0.0001). Both tasks were moderately accurate in discriminating CG from MCI (VFa: AUC = 0.68 +/- 0.04, p < 0.0001 - VFf:AUC = 0.73 +/- 0.04, p < 0.0001) regardless of the schooling level, and MCI from AD in the total sample (VFa: AUC = 0.74 +/- 0.05, p < 0.0001; VFf: AUC = 0.76 +/- 0.05, p < 0.0001). Neither of the two tasks differentiated low educated MCI from AD. In the total sample, fruits fluency best discriminated CG from MCI and MCI from AD; a combination of the two improved the discrimination between CG and AD. Conclusions: Both categories were similar in discriminating CG from AD; the combination of both categories improved the accuracy for this distinction. Both tasks were less accurate in discriminating CG from MCI, and MCI from AD.

THE EFFECTS OF BROMAZEPAM ON THE PERFORMANCE OF A SENSORY-MOTOR ACTIVITY: AN ELECTROENCEPHALOGRAPHIC STUDY

Aims. To investigate the effects of using bromazepam on the relative power in alpha while performing a typing task. Bearing in mind the particularities of each brain hemisphere, our hypothesis was that measuring the relative power would allow its to investigate the effects of bromazepam oil specific areas of the cortex. More, specifically, we expected to observe different patterns of powers in sensory-motor integration, attention and activation processes. Subjects and methods. The sample was made up of 39 subjects (15 males and 24 females) with a mean age of 30 +/- 10 years. The control (placebo) and experimental (3 mg and 6 mg of bromazepam) groups were trained ill the typing task with a randomised double-blind model. Results. A three-way ANOVA and Scheffe test were used to analyse interactions between the factors condition and moment, and between condition and sector Conclusions. The doses used ill this study facilitated motor performance of the typing task. Ill this study, the use of the drug did not prevent learning of the task, but it did appear to concentrate mental effort on more restricted and specific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed during mechanisms related to the encoding and storage often, information. Likewise, a predominance of activity was observed in the left (dominant) frontal area in the 3 mg bromazepam group, which indicates that this close of the drug affords the subject a greater degree of directionality of cortical activity for planning and performing the task. [REV NEUROL 2009; 49: 295-9]