Search

Purpose: The GRIN2A gene has been associated with epilepsies ranging from benign focal childhood epilepsies to severe epileptic encephalopathies. The aim of this study was to evaluate genotypes and phenotypes in individuals with GRIN2A deletions or variants. Method: We compared genotypes and phenotypes in six newly identified patients with GRIN2A variants with those of 149 individuals with GRIN2A variants from the literature. Results: Six new patients with epilepsy, developmental and/or behavioral problems and GRIN2A deletions (n = 3), missense (n = 2) or splice-site variants (n = 1) are presented. In 125 (84%) of the 149 individuals with GRIN2A variants previously reported, a specific epilepsy syndrome was diagnosed, most often classified as Benign Epilepsy with Centro-Temporal Spikes (BECTS; n = 44) or Landau-Kleffner syndrome/ Continuous Spike-And-Waves during Slow-wave sleep (LKS/ CSWS; n = 42). Problems of speech and language development (81%), cognition (68%), motor skills (50%) or behavior (42%) were common. Missense variants were seen in 52% of the patients reported earlier, more often in individuals with BECTS (71%) compared to those with LKS/ CSWS (48%). Certain missense variants in or close to the ligand-gated ion channel domain were associated with a severe phenotype, as was also observed in two of our patients with severe epilepsy and cognitive impairment. Conclusion: Individuals with GRIN2A gene variants or deletions have an extremely variable phenotype without a clear genotype-phenotype correlation. Variants in or close to the ligand-gated ion channel can be associated with a severe phenotype.

Gras and colleagues present the results of an interesting and accurate study on the clinical phenomenology and long-term prognosis of a large series of 28 patients with genetically confirmed benign hereditary chorea (BHC).1 BHC is a rare genetic condition with an autosomal dominant pattern of inheritance. The defects have been identified in mutations affecting the TIFT1 gene (now named NKX2-1), which encodes the thyroid transcription factor 1, while the clinical phenotype has traditionally been defined by the triad of chorea, hypothyroidism and lung disease (‘brain-thyroid-lung syndrome’). Specifically, the clinical picture of BHC has long been thought to be characterised by childhood …

Background Diarrhea is a leading cause of morbidity among children under 5 years of age in low- and middle-income countries yet the additional effects and sequelae, such as cognitive impairment associated with diarrhea, have not been quantified. Methods We quantified the association between diarrhea prevalence and cognitive outcomes while controlling for linear growth in 4 study populations. Cognition was assessed using different methods across sites and was expressed in standardized units. We built linear regression models for each study with standardized cognitive score as the outcome and diarrhea prevalence as the main predictor variable. We then conducted meta-analyses of the regression coefficients to generate pooled estimates of the association between diarrhea prevalence and cognition whilst controlling for anthropometric status and other covariates. Results Diarrhea was not a significant predictor of cognitive score in any site in the regression models or in the meta-analyses (Coefficient = 0.07; 95% CI: −0.1, 0.2). The length for age Z- score was negatively related to cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably similar across sites (Coefficient Range: 0.168–0.186). Conclusions We did not demonstrate an association between diarrhea and cognition with stunting included in the model. The links between diarrhea, stunting, and cognition provide additional rationale for accelerating interventions to reduce diarrhea.

Falls are frequent among patients with debilitating disorders and can have a serious effect on health status. Mild cognitive disturbances associated with cirrhosis may increase the risk for falls. Identifying subjects at risk may allow the implementation of preventive measures. Our aim was to assess the predictive value of the Psychometric Hepatic Encephalopathy Score (PHES) in identifying patients likely to sustain falls. One hundred and twenty-two outpatients with cirrhosis were assessed using the PHES and were followed at specified intervals. One third of them exhibited cognitive dysfunction (CD) according to the PHES (

Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p, Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.

Objectives: In a multi-site population-based study in several middle-income countries, we aimed to investigate relative contributions of care arrangements and characteristics of carers and care recipients to strain among carers of people with dementia. Based on previous research, hypotheses focused on carer sex, care inputs, behavioural and psychological symptoms (BPSD) and socioeconomic status, together with potential buffering effects of informal support and employing paid carers. Methods: In population-based catchment area surveys in 11 sites in Latin America, India and China, we analysed data collected from people with dementia and care needs, and their carers. Carer strain was assessed with the Zarit Burden Interview. Results: With 673 care recipient/carer dyads interviewed (99% of those eligible), mean Zarit Burden Interview scores ranged between 17.1 and 27.9 by site. Women carers reported more strain than men. The most substantial correlates of carer strain were primary stressors BPSD, dementia severity, needs for care and time spent caring. Socioeconomic status was not associated with carer strain. Those cutting back on work experienced higher strain. There was tentative evidence for a protective effect of having additional informal or paid support. Conclusions: Our findings underline the global impact of caring for a person with dementia and support the need for scaling up carer support, education and training. That giving up work to care was prevalent and associated with substantial increased strain emphasizes the economic impact of caring on the household. Carer benefits, disability benefits for people with dementia and respite care should all be considered.

Oxidative stress and neuroinflammation play important roles in Alzheimer's disease (AD). ABCG2 is a transporter protein expressed in the brain and involved in GSH transport. To study the roles of Abcg2 in oxidative stress and AD, we cross-bred Tg-SwDI and Abcg2-KO mice and generated Tg-SwDI/Abcg2-KO (double-tg) mice. Brain tissues from double-tg, Tg-SwDI, wild-type, and Abcg2-KO mice at various ages were analyzed. Aβ40 and Aβ42 were detected in Tg-SwDI and double-tg mice. Total brain GSH was decreased and levels of lipid/DNA oxidation were increased in 3-month double-tg compared to Tg-SwDI mice. Low brain GSH was still detected in 9-month double-tg mice. Increased HMOX-1 and MCP-5 expression was observed in 9-month double-tg mice but not in Tg-SwDI mice compared to WT and Abcg2-KO mice. Increased HMOX-1 and decreased ICAM-1 expression were observed in 12-month double-tg mice compared to Tg-SwDI mice. The levels of Nrf-2 expression and activity were decreased in 6-month double-tg mice. Behavioral tests show impaired cognitive/memory performance of 9-month double-tg compared to Tg-SwDI mice as well as WT and Abcg2-KO mice. These results suggest that Abcg2 deficiency increases oxidative stress and alters inflammatory response in the brain and exacerbates cognitive/memory deficit in double-tg mice at different developmental stages. © 2012 National Research Council Canada & The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

[No abstract available]

Objective: The ability to make inferences about knowledge, thoughts and feelings of others, i.e. perspective taking, is a key element of social cognition. Clinical observations indicate that Korsakoff patients may have impairments in social cognition, but studies are scarce. Also, executive dysfunction is present in Korsakoff patients, which may hamper perspective taking directly. Methods: Twenty-three patients with Korsakoff's syndrome and 15 healthy matched controls were examined on a story comprehension task, in which inferences had to be made that either relied on perspective taking or not. The effects of task complexity were taken into account and executive function was assessed using an extensive neuropsychological test battery. Results: The performance of Korsakoff patients declined with increasing complexity, but the pattern of decline for perspective-taking and non-perspective-taking stories was similar compared to that of the control group. Furthermore, the performance decline with increasing task complexity was directly related to the overall decline in executive functioning. Conclusion: Executive dysfunction, not deficits in perspective taking per se, appears to underlie difficulties in story comprehension in patients with Korsakoff's syndrome.

Background: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. There is a limited literature linking short legs and small skulls to an increased risk for cognitive impairment and dementia in late life.Methods: One phase cross-sectional surveys were carried out of all residents aged over 65 years in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru (n = 14,960). The cross-culturally validated 10/66 dementia diagnosis, and a sociodemographic and risk factor questionnaire were administered to all participants, and anthropometric measures taken. Poisson regression was used to calculate prevalence ratios for the effect of leg length and skull circumference upon 10/66 dementia, controlling for age, gender, education and family history of dementia.Results: The pooled meta-analyzed fixed effect for leg length (highest vs. lowest quarter) was 0.82 (95% CI, 0.68–0.98) and for skull circumference 0.75 (95% CI, 0.63–0.89). While point estimates varied between sites, the proportion of the variability attributable to heterogeneity between studies as opposed to sampling error (I2) was 0% for leg length and 22% for skull circumference. The effects were independent and not mediated by family history of dementia. The effect of skull circumference was not modified by educational level or gender, and the effect of leg length was not modified by gender.Conclusions: Since leg length and skull circumference are said to remain stable throughout adulthood into old age, reverse causality is an unlikely explanation for the findings. Early life nutritional programming, as well as neurodevelopment may protect against neurodegeneration.

Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007). Despite the prevalence of co-administration of MDMA and THC, the effects of combined use of these substances on behaviour in humans have so far not been investigated. The aim of the present study was to assess the acute effects of (co-) administration of MDMA and THC (the main psychoactive compound of cannabis) on pharmacokinetics, psychomotor performance, memory and subjective experience over time. Methods: We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (12 male, 4 female) between the ages of 18 and 27. MDMA (100 mg) was given orally, THC (4, 6, and 6 mg, interval of 90 minutes) was vaporized and inhaled. Outcome measures were assessed repeatedly, i.e. before MDMA administration and at 15, 60, 105, 150, 240 and 300 minutes post drug administration, with the exception of the 18 word list memory task, which was performed 120 minutes after drug administration. Repeated measures consisted of blood sampling for analysis of study drug kinetics and assessments of postural stability (body sway), psychomotor function (eye movements and the Rotor Pusuit Task), memory (18 word list and N-back task), and subjective effects (VAS). Results: Body sway was increased, i.e. postural position was impaired, in all drug conditions compared to placebo. THC alone as well as co-administration of THC plus MDMA increased body sway compared to the MDMA alone condition. Eye movements were unaffected by THC, MDMA increased the peak velocity of eye movements. The Rotor Pursuit task (see Figure 1) performance was significantly impaired in the THC condition and the MDMA plus THC condition compared to the placebo and MDMA condition. MDMA alone did not affect the Rotor Pursuit task. Immediate recall of words was impaired in all drug conditions compared to placebo. Delayed recall and delayed recognition did not show a significant main effect of drug administration. The effects of (co-administration) of THC on the N-back working memory task were time- and dose dependent, where THC generally induced a robust but short-lived impairment of working memory. N-back performance was unaffected in the MDMA condition. Co-administration of THC and MDMA enhanced separate subjective drug effects: ratings of 'drug strength', 'internal and external perception', and 'feeling high' were increased compared to the MDMA condition. Conclusion: These results suggest that THC may exert much of its cognitive impairment via a common mechanism of reduced alertness. The stimulant effects of MDMA may attenuate this effect, but could not overcome THC induced impairments in the current study. Overall, THC induced more robust cognitive impairment compared to MDMA. Co-administration of THC with MDMA increased desired subjective drug effects and drug strength compared to the MDMA condition, which may explain the widespread use of this combination.

Introduction: Falls in psychogeriatric residents represent a costly but unresolved safety issue. Identifying fall risk factors and their inter-relationship may help to individualize prevention programs and increase the effectiveness. Therefore, we aimed to examine the relationship between patient characteristics and fall rate in psychogeriatric residents. Methods: Twenty nursing home residents with dementia (80±11 years; 60% male) living on a psychogeriatric ward participated. Based on patient records, we identified 66 patient characteristics and extracted the number of falls over 19 months. Patient characteristics represented seven domains: demographics, ADL, mobility, cognition and behaviour, vision and hearing, medical conditions, and drug-use. We evaluated the relationship between patient characteristics and fall rate using multivariate Partial Least Squares regression. Results: A total of 115 falls (5.1±6.7 falls/person year) occurred during the study period. The 66 patient characteristics included in the model explained 96% of the variance in fall rate. Reduced mobility abilities, indicators of disinhibited behavior, diabetes, and use of analgesics, beta blocking agents and psycholeptics were positively associated with fall rate. Whereas immobility, heart failure, and the inability to communicate were negatively associated fall rate. Conclusion: Dementia is often indicated as fall risk factor; however, our results showed that especially cognitive impairment related to disinhibited behaviour was associated with a high fall rate in psychogeriatric residents. Furthermore, immobility and inactivity seemed to decrease fall rate. The analytic approach provided a detailed view of the fall risk factors and their interactions in psychogeriatric residents, enabling more effective fall prevention.

Update on the Montreal Cognitive Assessment (MoCA) (J.F.M. de Jonghe): This presentation aims to provide an overview of item content of the Montreal Cognitive Assessment (MoCA) and an update of studies using the MoCA in different patient populations. The MoCA assesses several cognitive domains including episodic memory (by two learning trials of five nouns and a delayed recall task), constructional praxis (by a clock-drawing task and a three-dimensional cube copy), executive function (by a short form of the Trail-making task part B), a phonemic fluency task, a verbal abstraction task, attention and working memory (by a sustained attention task, a serial subtraction task, and digits forward and backward), language (by a confrontation naming task, repetition of two sentences, and a fluency task). Finally, orientation to time and place is also evaluated. The MoCA measures these different cognitive domains with less ceiling effects in patients who have mild degrees of cognitive impairment. Thereby, the MoCA is a promising tool for detecting Mild Cognitive Impairment (MCI) and Early Alzheimer's disease compared to the MMSE. The MoCA has been used to assess patients with Parkinson's disease, vascular cognitive impairment, Huntington's disease, metastatic disease in the brain, primary brain tumors, multiple sclerosis, and other conditions including traumatic brain injury, depression, schizophrenia and heart failure. We conclude that the MoCA is a very useful new cognitive screening that has been validated in different patient populations. Seven Minute Screen (7MS) in a secondary care setting (B. Appels): Earlier studies showed that despite its limitations, the MMSE was by far the most commonly used instrument. In the last decades, many new dementia screening instruments have been developed in order to meet the shortcomings of the MMSE. The Seven Minute Screen (7MS) is one of these instruments. The 7MS is a dementia screening test that was originally developed to distinguish patients with probable AD from healthy controls. It consists of four brief neuropsychological tests that measure orientation in time, memory, visuospatial and executive functions. The test is available in several languages and validated in a primary care as well as in secondary care settings. In this presentation, the findings of the normative and validation study in the Netherlands in a secondary care setting (memory clinics) will be demonstrated. The results outline the sensitivity of the 7MS in mild forms of Alzheimer disease but also other forms of dementia such as vascular dementia, frontotemporal dementia and dementia with Lewy bodies. The comparison with the MMSE is made to show the superiority of the 7MS in the sense that it combines the brief administration time of the MMSE with a higher diagnostic accuracy in detecting dementia. The Cross Cultural Dementia Screening Test (CCD) in comparison to MMSE in an elderly migrant population at the memory clinic (M. Goudsmit): With the aging population in the Netherlands and other European countries, elderly migrants will form a substantial part of the elderly population in the next decade. In the Netherlands, these migrants came mostly from Turkey, Morocco and Surinam. Cognitive decline and dementia are difficult to assess with standard cognitive screening instruments in elderly migrants primarily because of language barriers but also because many migrants have low levels of education and different cultural backgrounds. At the same time, prevalence of dementia is expected to be higher due to different contributing factors such as vascular risk factors. In general, commonly used cognitive screening instruments such as the MMSE have limited applicability for non-Western elderly migrants because of the high rate of false-positive results. We developed a new non-verbal dementia screening test, suitable for the low-educated migrant population. This Cross Cultural Dementia Screening Test (CCD) exists of three subtests, which evaluate memory, executive function and psychomotor speed. Although the test materials are non-verbal, instructions are given by means of computerized voice samples in a patient's native language. Test taking is possible without an interpreter. The newly developed CCD correctly classified 89% of cases in a sample of 108 low educated elderly migrants, of which half were demented and the other half were healthy controls. Compared to other screening instruments, such as the MMSE, the CCD seems to be more accurate in this migrant population. We will present data about this comparison in the lecture. Tailoring the cognitive test to the individual patient using adaptive cognitive testing (H. Wouters): This presentation aims to give an overview of our findings about Computerized Adaptive Testing (CAT) from the past five years. CAT is a potential solution to the well-known problem that longer cognitive tests, such as the Cambridge Cognitive Examination (CAMCOG), are more precise but also less efficient than briefer tests, such as the MMSE. CAT resolves this problem by tailoring the cognitive test to the individual patient. It selects for each individual patient only items of appropriate difficulty from a large pool of items with known difficulty estimates. Two retrospective analyses of data from normal ageing participants and patients with AD (N = 797) and CVD (N = 284) showed that substantial test reductions were achieved (∼40-60%) with a CAT version of the CAMCOG (CAT-CAMCOG). At the same time, agreement between the CATCAMCOG and a whole validated item pool of CAMCOG items was high to excellent (intraclass correlations >0.95). A prospective study (N = 84) corroborated these findings. A recent retrospective analysis of data from patients with AD and LBD (N = 643) was conducted to examine whether the CAT-CAMCOG could be as useful as the whole CAMCOG for the evaluation of treatment effects of cholinesterase inhibitors. The main finding was that slightly more people had significant decline on the CAMCOG (11%) than the CAT-CAMCOG (6%). Taken together, CAT saves time and obtains very similar test results. CAT therefore deserves a role for the screening of dementia and the grading of its severity.

Background: The risk for psychosis is increased for ethnic minorities. Much less is known about ethnic differences in cognitive deficits and their relationship with course and functional outcome. Goal: Explore relationships between ethnicity, cognitive deficits and outcome measures at baseline and 6 months follow up in a multi-ethnic sample of first episode psychosis patients. Method: Cases: All patients who made first-contact during a 1-year period and completed psychological assessment at baseline. Estimates ofinclusions per November 01, 2010: Baseline: n = 140; Follow up: n = 45. Instruments: 15 different neuropsychological instruments are used to assess seven cognitive domains: Memory, Attention, Speed of Processing, Reasoning, Verbal learning, Visual learning and Social Cognition. Outcome measures: Global Assessment of Functioning scale (GAF), Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Statistical analysis: Cases are grouped per ethnicity. Differences between groups are tested with independent sample T-tests, ANOVA, regression analyses and multi-level analyses. Covariates: Level of education, gender and age. Results: Preliminary analyses of baseline measures showed significant differences between ethnic minority patients and Dutch patients on all seven domains. Ethnic minority patients had lower scores, especially in the domains of Attention, Visual Learning, Speed of Processing and Social Cognition. Follow-up data on course and functional outcome will be presented. Conclusion: Marked differences are apparent between Dutch and ethnic minority patients at baseline on all seven cognitive domains. Potential explanations include cross-cultural bias in measurements and more severe psychopathology in the ethnic minority subgroup.

Background: The risk for psychosis is increased for ethnic minorities. Much less is known about ethnic differences in cognitive deficits and their relationship with course and functional outcome. Goal: Explore relationships between ethnicity, cognitive deficits and outcome measures at baseline and 6 months follow up in a multi-ethnic sample of first episode psychosis patients. Method: Cases: All patients who made first-contact during a 1-year period and completed psychological assessment at baseline. Estimates ofinclusions per November 01, 2010: Baseline: n = 140; Follow up: n = 45. Instruments: 15 different neuropsychological instruments are used to assess seven cognitive domains: Memory, Attention, Speed of Processing, Reasoning, Verbal learning, Visual learning and Social Cognition. Outcome measures: Global Assessment of Functioning scale (GAF), Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Statistical analysis: Cases are grouped per ethnicity. Differences between groups are tested with independent sample T-tests, ANOVA, regression analyses and multi-level analyses. Covariates: Level of education, gender and age. Results: Preliminary analyses of baseline measures showed significant differences between ethnic minority patients and Dutch patients on all seven domains. Ethnic minority patients had lower scores, especially in the domains of Attention, Visual Learning, Speed of Processing and Social Cognition. Follow-up data on course and functional outcome will be presented. Conclusion: Marked differences are apparent between Dutch and ethnic minority patients at baseline on all seven cognitive domains. Potential explanations include cross-cultural bias in measurements and more severe psychopathology in the ethnic minority subgroup.

Background: The risk for psychosis is increased for ethnic minorities. Much less is known about ethnic differences in cognitive deficits and their relationship with course and functional outcome. Goal: Explore relationships between ethnicity, cognitive deficits and outcome measures at baseline and 6 months follow up in a multi-ethnic sample of first episode psychosis patients. Method: Cases: All patients who made first-contact during a 1-year period and completed psychological assessment at baseline. Estimates ofinclusions per November 01, 2010: Baseline: n = 140; Follow up: n = 45. Instruments: 15 different neuropsychological instruments are used to assess seven cognitive domains: Memory, Attention, Speed of Processing, Reasoning, Verbal learning, Visual learning and Social Cognition. Outcome measures: Global Assessment of Functioning scale (GAF), Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Statistical analysis: Cases are grouped per ethnicity. Differences between groups are tested with independent sample T-tests, ANOVA, regression analyses and multi-level analyses. Covariates: Level of education, gender and age. Results: Preliminary analyses of baseline measures showed significant differences between ethnic minority patients and Dutch patients on all seven domains. Ethnic minority patients had lower scores, especially in the domains of Attention, Visual Learning, Speed of Processing and Social Cognition. Follow-up data on course and functional outcome will be presented. Conclusion: Marked differences are apparent between Dutch and ethnic minority patients at baseline on all seven cognitive domains. Potential explanations include cross-cultural bias in measurements and more severe psychopathology in the ethnic minority subgroup.

Objectives: The diversity of physical and cognitive impairments seen in Multiple Sclerosis (MS), make it difficult to make the definition and classification of physical and cognitive disabilities and to identify the factors that influence neurorehabilitation programs and outcomes. In the view of the complexities of both Multiple Sclerosis (MS) and the rehabilitation process, this preliminary study's aim was to determine the cognitive dysfunctions by conducting on early term relapsing-remitting MS (RRMS) patients. Methodology: Cognitive performances of 27 early term RRMS patients and 27 individually s ex-age matched volunteer healthy controls (HC) were compared. Each patient underwent a complete clinical assessment, including depression, disability and comprehensive cognitive function [attention: Stroop tests, memory and perception: Wechsler Memory Scale-Revised (WMS-R) subtests]. Results: There were statistically significant differences between groups for all subtests of Stroop (p

Anti-epileptic drugs (AEDs) have a variety of mechanisms of action which are reflected through different anticonvulsant activities and behavioral effects. Two categories of AEDs are considered based on psychotropic profile. The first group is characterized by potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission, and comprises of agents such as vigabatrin, tiagabine, and gabapentin. These agents are noted to have sedating effects ranging from cognitive slowing to anti-manic effects. On the other hand, the second group is typified by attenuation of glutamate excitatory neurotransmission and has activating effects including anxiogenic and antidepressant actions. Lamotrigine and felbamate feature in this latter group. Mechanisms of action, chief clinical indications, as well as behavioral profile including comment on chief cognitive effects of the newer AEDs are reviewed in accordance with this dual categorization. In clinical practice, assessment of an individual patient alongside consideration of AED behavioral profile primes for appropriate prescription according to patient mood profile, also permitting exposure of AED-induced behavioral disturbance.

Background: Prader-Willi syndrome (PWS) is the most common known genetic cause of life-threatening obesity in children. The purpose of the study was to present the case of a delayed diagnosis of PWS in a 24-year-old male and the importance of an early PWS diagnosis as well as behavioral and institutional treatment issues. Case Report: A young man presented with a history of hyperphagia, severe obesity, and mental retardation. From his history, laboratory data, and molecular analysis using a DNA marker it was decided that he was affected by PWS. Conclusions: As healthcare professionals, we emphasize the need for approaching each person who has PWS as an individual and to be sensitive to traits and choose the most appropriate therapeutic approach. © The American Journal of Case Reports, 2010. 11 50 53

Background: Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings: We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance: A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation. © 2010 Go ́mez Ravetti et al.

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family, and is widely expressed in the adult mammalian brain. Besides its well known neuroprotective activity after traumatic brain injury the evidences regarding its activity dependent release by the pathophysiology of major depression are rapidly replicating. Considering the data that stress plays an important role by the development of depression which is characterized with prominent hippocampal cell death, as well as the well known neuroprotective effects of BDNF, we aimed to investigate the link between the BDNF, stress and depression. Thus we prepared a minireview in order to evaluate the neuroprotective role of BDNF by psychiatric disorders which are characterized with prominent neuronal cell death.

To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep–wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and the oxime HI-6 for reactivation of soman-inhibited acetylcholinesterase. We also investigated whether sub-chronic treatment with the reported neurogenesis enhancer olanzapine would stimulate neurogenesis and possibly normalize the anticipated long-term deleterious effects of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed after 30 min by soman (200 mg/kg s.c.) and atropine sulphate (16 mg/kg i.m.) 1 min thereafter. Soman poisoning led to an elevation of extracellular acetylcholine levels to 1500% over baseline values as assessed by striatal microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24 h post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU labeled. Learning and memory performance were assessed 8 weeks after soman poisoning, followed by analysis of surviving newborn cells (BrdU) and neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a significantly impaired learning ability was found that was paralleled by significantly lower numbers of DCX-positive cells but no changes in the number of BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. We conclude that soman poisoning has long lasting effects on learning ability, a finding that was accompanied by impaired neurogenesis. Although we confirm a correlation between impaired neurogenesis and cognitive deficits, establishing the true causal relationship between these processes in OP exposed animals awaits future research.

Purpose: Post stroke depression is seen frequently and causes delays in recovery of the patient, worsens functional status and makes a negative impact on quality of life. Cognitive disorders are also seen frequently and after 3 months demential findings are observed in 1/4 of patients. The aim of our study was to compare cognitive functions and emotional status of patients administered for stroke at our clinic within first week with the healthy subjects who were at similar age and gender. Patients and methods: Mini-Mental State Examination (MMSE), National Institute of Health Scale, Barthel Scale and Beck Depression Scale are applied to the 30 patients who were hospitalized for acute stroke to detect emotional status, cognitive function and severity of stroke. MMSE and Beck depression scales were applied to 30 healthy people as control group. Two groups are compared by student t test. Results: The mean values of Beck Depression Scale for patient group and control group were 15.2±10.5 and 8.8±4.2 respectively (p=0.001). The mean values of MMSE for post stroke group and control group were 25.8±4.7 and 27.9±1.7 respectively (p=0.032). There was no correlation between Beck Scale and stroke scales. Conclusion: Our study detected that cognitive functions and emotional status are impaired at post stroke patients when compared with the healthy people at the same age and gender.

Objective: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. Methods: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. Results: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (

Contains fulltext : 80142.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. METHODS: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. RESULTS: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (

To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and the oxime HI-6 for reactivation of soman-inhibited acetylcholinesterase. We also investigated whether sub-chronic treatment with the reported neurogenesis enhancer olanzapine would stimulate neurogenesis and possibly normalize the anticipated long-term deleterious effects of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed after 30 min by soman (200 μg/kg s.c.) and atropine sulphate (16 mg/kg i.m.) 1 min thereafter. Soman poisoning led to an elevation of extracellular acetylcholine levels to 1500% over baseline values as assessed by striatal microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24 h post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU labeled. Learning and memory performance were assessed 8 weeks after soman poisoning, followed by analysis of surviving newborn cells (BrdU) and neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a significantly impaired learning ability was found that was paralleled by significantly lower numbers of DCX-positive cells but no changes in the number of BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. We conclude that soman poisoning has long lasting effects on learning ability, a finding that was accompanied by impaired neurogenesis. Although we confirm a correlation between impaired neurogenesis and cognitive deficits, establishing the true causal relationship between these processes in OP exposed animals awaits future research. © 2008 Elsevier Inc. All rights reserved.

Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI. Interventions : The 152 participants were randomly assigned to two interventions: (1) a twice-weekly, group-based, moderate-intensity walking programme (WP, n = 77) or a low-intensity placebo activity programme (n = 75) for one year; and (2) daily vitamin pill containing 5 mg folic acid, 0.4 mg vitamin B-12, 50 mg vitamin B-6 (FA/B12/B6, n = 78) or placebo pill (n = 74) for one year. Outcome measures: Cognitive function, measured with neuropsychological tests at baseline and after six and 12 months. Results: Median session attendance at the exercise programmes (25th-75th percentile) was 63% (2%-81%) and median compliance with taking pills (25th-75th percentile) was 100% (99%-100%). Gender was an effect modifier. Intention-to-treat analysis revealed no main intervention effect for either intervention. In women in the WP, attention (Stroop combination task) improved by 0.3 seconds (p = 0.04) and memory (auditory verbal learning test) by 0.04 words (p = 0.06) with each percentage increase in session attendance. In men attending at least 75% of the sessions, the WP improved memory (β 1.5 (95% CI: 0.1 to 3.0) words). Conclusion: The walking programme and/or FA/B12/B6 supplementation were not effective in improving cognition within one year. The walking programme, however, was efficacious in improving memory in men and memory and attention in women with better adherence. Trial registration: International Standard Randomised Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/. Chemicals / CAS: Folic Acid, 59-30-3; Vitamin B 12, 68-19-9; Vitamin B 6, 8059-24-3

Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI. Interventions : The 152 participants were randomly assigned to two interventions: (1) a twice-weekly, group-based, moderate-intensity walking programme (WP, n = 77) or a low-intensity placebo activity programme (n = 75) for one year; and (2) daily vitamin pill containing 5 mg folic acid, 0.4 mg vitamin B-12, 50 mg vitamin B-6 (FA/B12/B6, n = 78) or placebo pill (n = 74) for one year. Outcome measures: Cognitive function, measured with neuropsychological tests at baseline and after six and 12 months. Results: Median session attendance at the exercise programmes (25th-75th percentile) was 63% (2%-81%) and median compliance with taking pills (25th-75th percentile) was 100% (99%-100%). Gender was an effect modifier. Intention-to-treat analysis revealed no main intervention effect for either intervention. In women in the WP, attention (Stroop combination task) improved by 0.3 seconds (p = 0.04) and memory (auditory verbal learning test) by 0.04 words (p = 0.06) with each percentage increase in session attendance. In men attending at least 75% of the sessions, the WP improved memory (β 1.5 (95% CI: 0.1 to 3.0) words). Conclusion: The walking programme and/or FA/B12/B6 supplementation were not effective in improving cognition within one year. The walking programme, however, was efficacious in improving memory in men and memory and attention in women with better adherence. Trial registration: International Standard Randomised Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/. Chemicals / CAS: Folic Acid, 59-30-3; Vitamin B 12, 68-19-9; Vitamin B 6, 8059-24-3

Objective: To test whether subcortical vascular lesions are associated with falls in elderly patients with gait disorder discharged from a rehabilitation ward. Design: Secondary 12-month follow-up analysis of an observational survey focusing on the prevalence of subcortical vascular lesions in a population of elderly patients discharged from rehabilitation hospitals. Setting: A rehabilitation and aged care unit. Participants: Consecutively admitted elderly patients (N=214) with gait disorder. Interventions: Not applicable. Main Outcome Measures: On admission, all patients underwent comprehensive geriatric assessment including sociodemographics, cognitive and depressive symptoms, nutritional status, physical health, and functional status. Subcortical vascular lesions were assessed on computed tomography films with a validated rating scale. All patients received a standardized rehabilitative program. Twelve months after discharge, all patients were interviewed by telephone, mainly focusing on the occurrence of falls during the follow-up period. Potential predictors of falls were assessed in univariate and multivariate analyses. Results: Univariate predictors of falls were age, sex, Mini-Mental State Examination, Barthel Index on admission, and subcortical vascular lesions. In multivariate analyses, subcortical vascular lesions were the only significant predictor of risk of falling; patients with moderate and severe subcortical vascular lesions scores had a greater risk of falling (odds ratio [OR]=3.0; 95% confidence interval [CI], 1.3-7.1; P=.012; OR=3.9; 95% CI, 1.6-9.2; P=.002, respectively) than those with no subcortical vascular lesions. Conclusions: Subcortical vascular lesions are associated with falls at 12 months in elderly patients with gait disorder discharged from a rehabilitative ward. Future research is needed to confirm our results. © 2008 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.