João Vinícius Salgado

The Rey Auditory-Verbal Learning Test: applicability for the Brazilian elderly population

OBJECTIVE The Rey Auditory-Verbal Learning Test is a widely recognized test in neuropsychological literature to evaluate learning and memory. This paper presents the performance of six age groups of Brazilian elderly on the Rey Auditory-Verbal Learning Test. METHOD A version of the test was developed with a list of high-frequency one-syllable and two-syllable concrete Portuguese substantives. Two hundred and twenty-three subjects of both genders were allocated to 6 age groups (60-64, 65-69; 70-74; 75-79; 80-84 and 85-89 years old) and tested with the Rey Auditory-Verbal Learning Test. RESULTS Educational level and age had a positive and a negative correlation, respectively, with performance on the Rey Auditory-Verbal Learning Test. Women performed significantly better than men. Our results were similar to those found for the Rey Auditory-Verbal Learning Test English version, across similar age ranges. CONCLUSION Our results suggest that the Brazilian Portuguese Rey Auditory-Verbal Learning Test adaptation was adequate and applicable for evaluating the memory capacity of Brazilian subjects, across similar age and educational levels.

Executive dysfunction in euthymic bipolar disorder patients and its association with plasma biomarkers

BACKGROUND Despite the old Kraepelinean concept that bipolar disorder (BD) does not evolve with cognitive decline, the presence of cognitive impairment, especially executive dysfunction has been recognized in BD patients. Brain-derived neurotrophic factor (BDNF) and pro-inflammatory molecules are important contributors to the pathophysiology of BD, and imbalance in peripheral levels of these molecules may be implicated in the cognitive decline observed in BD patients. We aimed to investigate the executive performance of BD type I euthymic patients and its relation with the plasma levels of BDNF, TNF-α and its related soluble receptors (sTNFR1 and sTNFR2). METHODS We evaluated executive functioning through the Frontal Assessment Battery (FAB). Plasma levels of BDNF, TNF-α, sTNFR1 and sTNFR2 were measured using enzyme-linked immunosorbent assay (ELISA) in 25 euthymic type I BD patients and 25 age and gender matched healthy controls. RESULTS BD patients had an impairment in executive functioning (p<0.006), particularly sensitivity of interference (p=0.02), inhibitory control (p=0.02), and increased BDNF plasma levels (p=0.001) in comparison with controls. Plasma levels of TNF-α were correlated with inhibitory control in BD patients (ρ=0.50, p=0.02) while motor programming was negatively correlated with sTNFR2 plasma levels (ρ=-0.47, p=0.02) in controls. Executive function correlated with age and MMSE, but not with BDNF, neither was influenced by psychiatric and clinical comorbidities nor medications in use. CONCLUSION BDNF is altered in BD but do not correlate with executive functioning.

Neuro-transmitters in the central nervous system & their implication in learning and memory processes.

This review article gives an overview of a number of central neuro-transmitters, which are essential for integrating many functions in the central nervous system (CNS), such as learning, memory, sleep cycle, body movement, hormone regulation and many others. Neurons use neuro-transmitters to communicate, and a great variety of molecules are known to fit the criteria to be classified as such. A process shared by all neuro-transmitters is their release by excocytosis, and we give an outline of the molecular events and protein complexes involved in this mechanism. Synthesis, transport, inactivation, and cellular signaling can be very diverse when different neuro-transmitters are compared, and these processes are described separately for each neuro-transmitter system. Here we focus on the most well known neuro-transmitters: acetyl-choline, catechol-amines (dopamine and nor-adrenalin), indole-amine (serotonin), glutamate, and gamma-amino-butyric acid (GABA). Glutamate is the major excitatory neuro-transmitter in the brain and its actions are counter-balanced by GABA, which is the major inhibitory substance in the CNS. A balance of neuronal transmission between these two neuro-transmitters is essential to normal brain function. Acetyl-choline, serotonin and catechol-amines have a more modulatory function in the brain, being involved in many neuronal circuits. Apart from summarizing the current knowledge about the synthesis, release and receptor signaling of these transmitters, some disease states due to alteration of their normal neuro-transmission are also described.

Neuropsychological assessment of impulsive behavior in abstinent alcohol-dependent subjects

OBJECTIVE Poor impulse control is thought to be one of the characteristics of alcohol addiction. The capacity to remain abstinent may be linked to cognitive bias related to three dimensions of impulsivity: motor, non-planning, and attentional impulsivity. The aim of this study was to evaluate the neuropsychological profile related to these impulsivity dimensions in alcohol-dependent patients within 15 -120 days of abstinence. METHOD We compared 31 alcohol-dependent patients to 30 matched healthy controls regarding their performances on the Continuous Performance Task, the Iowa Gambling Test, and the Wisconsin Card Sorting Test, each of which is thought to tax primarily one of the three dimensions of impulsivity just outlined. RESULTS When compared to controls, alcohol-dependent patients presented more commission errors on the Continuous Performance Task; made more disadvantageous choices on the Iowa Gambling Test; and made more perseverative errors on the Wisconsin Card Sorting Test. There was no significant correlation between performance on these tests and the length of abstinence. CONCLUSIONS These results suggest that deficits related to motor, non-planning and attentional components of impulsivity exist in alcohol-dependent patients, in the period immediately after acute alcohol withdrawal. These results may help guide interventions designed to prevent the risk of relapse in alcohol-abstinent patients.

Midazolam-induced hyperalgesia in rats: modulation via GABAA receptors at supraspinal level

The effect of benzodiazepines on the nociceptive threshold was studied in rats using the tail-flick and the formalin tests. Systemic injection of midazolam (10 mg/kg, i.p.) induced a significant decrease of the tail-flick latency and produced a long-lasting nociceptive effect in the formalin test, thus characterising a hyperalgesic state. The hyperalgesia induced by midazolam in the tail-flick test was blocked by flumazenil, a specific antagonist for benzodiazepine sites associated with GABA(A) receptors. Picrotoxin, a Cl- channel blocker, inhibited midazolam-induced hyperalgesia in both tests. Midazolam caused hyperalgesia when administered intracerebroventricularly (i.c.v.; 25 microg) but not intrathecally (i.t.; 75 microg). I.c.v. but not i.t. (5 microg) injection of flumazenil suppressed the hyperalgesia induced by midazolam (10 mg/kg, i.p.). Combination of non-hyperalgesic doses of diazepam (10 mg/kg, i.p.) or ethanol (0.48 g/kg, oral) with midazolam (5 mg/kg, i.p.) also induced hyperalgesia. Our results demonstrate that midazolam and diazepam alone or in combination with ethanol can produce hyperalgesia by interacting with GABA(A) receptors at the supraspinal level in rats. The risk of hyperalgesia should be taken in account when these drugs are used in combination in humans.

Brazilian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

OBJECTIVE The purpose of this research was to evaluate the Brazilian-Portuguese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and to assess its psychometric properties. METHODS This study involved 98 outpatients who underwent psychopathological evaluation with the Mini International Neuropsychiatric Interview-Plus Version, Hamilton Depression Scale (HAM-D), and a Portuguese version of the NDDI-E. RESULTS The NDDI-E was easily understood and quickly administered to most of the patients. At a cutoff score >15, NDDI-E had a sensitivity of 81.5%, a specificity of 83.1%, and a negative predictive value of 92.2% for diagnosis of major depression. Internal consistency reliability of the NDDI-E was 0.79, and there was also a positive correlation between the NDDI-E and the HAM-D (P<0.001). CONCLUSION The Brazilian-Portuguese version of NDDI-E can be used as a practical screening tool to improve recognition of depression in Brazilian people with epilepsy.

Psychiatric disorders in temporal lobe epilepsy: An overview from a tertiary service in Brazil

PURPOSE To evaluate the frequency and intensity of psychiatric disorders in a group of temporal lobe epilepsy (TLE) patients from a tertiary-care center. METHODS Clinical and sociodemographic data of 73 patients were collected and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured clinical interview (MINI-PLUS), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Brief Psychiatric Rating Scale (BPRS). RESULTS Patients with TLE showed a high frequency of lifetime psychiatric disorders (70%), the most frequent being mood disorders (49.3%). At assessment, 27.4% of the patients were depressed and 9.6% met criteria for bipolar disorder. Nevertheless, depression had not been properly diagnosed nor treated. Anxiety disorders were also frequent (42.5%), mainly generalized anxiety disorder (GAD) (21.9%). Obsessive compulsive disorder (OCD) was present in 11.0% and psychotic disorders in 5.5% of the sample. Patients with left mesial temporal sclerosis (LMTS) exhibited more psychopathologic features, mainly anxiety disorders (p=0.006), and scored higher on HAM-A and HAM-D (p<0.05 in both). CONCLUSION TLE is related to a high frequency of psychiatric disorders, such as anxiety and depression, which are usually underdiagnosed and undertreated. Damage to the left mesial temporal lobe, seen in LMTS, seems to be an important pathogenic lesion linked to a broad range of psychopathological features in TLE, mainly anxiety disorders. The present study prompts discussion on the recognition of the common psychiatric disorders in TLE, especially on the Brazilian setting.

Applicability of the Rey Auditory-Verbal Learning Test to an adult sample in Brazil

OBJECTIVE The Rey Auditory-Verbal Learning Test, which is used to evaluate learning and memory, is a widely recognized tool in the general literature on neuropsychology. This paper aims at presenting the performance of Brazilian adult subjects on the Rey Auditory-Verbal Learning Test, and was written after we published a previous study on the performance of Brazilian elderly subjects on this same test. METHOD A version of the test, featuring a list of high-frequency one-syllable and two-syllable concrete Portuguese substantives, was developed. Two hundred and forty-three (243) subjects from both genders were allocated to 6 different age groups (20-24; 25-29; 30-34; 35-44; 45-54 and 55-60 years old). They were then tested using the Rey Auditory-Verbal Learning Test. RESULTS Performance on the Rey Auditory-Verbal Learning Test showed a positive correlation with educational level and a negative correlation with age. Women performed significantly better than men. When applied across similar age ranges, our results were similar to those recorded for the English version of the Rey Auditory-Verbal Learning Test. CONCLUSION Our results suggest that the adaptation of the Rey Auditory-Verbal Learning Test to Brazilian Portuguese is appropriate and that it is applicable to Brazilian subjects for memory capacity evaluation purposes and across similar age groups and educational levels.

Dopamine dysregulation syndrome in Parkinson's disease: case report

We report a 67-year-old man with Parkinsons disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.

Estudo Normativo do Token Test versão reduzida: dados preliminares para uma população de idosos brasileiros

INTRODUCAO: A preservacao das habilidades de compreensao da fala nos idosos esta correlacionada com a preservacao das funcoes cognitivas. Essa habilidade e caracteristica fundamental para a comunicacao e sua avaliacao possibilita a identificacao de deficits cognitivos mais especificos, alem de facilitar o desenvolvimento de estrategias de intervencao mais precoces e eficientes. OBJETIVO: Disponibilizar normas contemporâneas para a utilizacao de um instrumento de avaliacao da compreensao verbal, o Token Test, para idosos brasileiros saudaveis. METODO: Uma amostra com 120 idosos (76 mulheres), com medias de 71,1 anos para idade e de 6,9 anos de educacao formal para escolaridade, foi avaliada utilizando o Miniexame do Estado Mental, para identificacao da existencia de comprometimento cognitivo, e o Token Test, para avaliacao da compreensao da fala. RESULTADOS: Foram encontradas correlacoes significativas (p < 0,01) entre o escore do Token Test e a educacao formal e a idade, os quais corresponderam respectivamente a 5% e 21% da variância compartilhada. Tais variaveis foram consideradas nas tabelas normativas. CONCLUSAO:Nossos dados indicam que as normas disponibilizadas aqui sao suficientemente representativas. Este trabalho abre caminho para estudos futuros de comparacao entre o desempenho no Token Test de idosos saudaveis e daqueles em processos de declinio cognitivo.