Test UD Interferencia: Creación y validación de un nuevo instrumento de resistencia a la interferencia. Normalización y estandarización en población española / UD Interference Test: Creation and validation of a new instrument of resistance to interference. Normalization and standardization for Spanish population

Introducción: El test UD Interferencia evalúa la velocidad de procesamiento y la atención, y está basado en el concepto de interferencia del test de Stroop. El objetivo principal de este estudio es proporcionar una versión alternativa del test de Stroop que evite algunas de las limitaciones de versiones anteriores, relacionadas con el daltonismo y las dificultades de lectura en personas mayores, y obtener datos normativos y estandarizados para este test, adaptados a población española. Métodos: El estudio se enmarca dentro del proyecto Normacog, para el cual se evaluó a 905 participantes (18-93 años). Se analizó la fiabilidad y la validez concurrente y de constructo del test. Se analizaron el efecto de la edad, nivel educativo y sexo sobre el rendimiento en UD Interferencia y se crearon percentiles y puntuaciones escalares ajustadas por edad y nivel educativo. Resultados: El test muestra buena fiabilidad (α = 0,875) y validez concurrente (r de 0,443 a 0,725; p < 0,001) y de constructo (r de 0,472 a 0,737; p < 0,001). Se observó un efecto significativo de la edad y el nivel educativo sobre el rendimiento en UD Interferencia, explicando del 12 al 40% de la varianza. El sexo únicamente presentó un efecto significativo en la variable índice de resistencia a la interferencia. Conclusiones: Se presenta una versión alternativa del test de Stroop que presenta algunas ventajas sobre anteriores versiones. Se aportan baremos estandarizados y normalizados para población española que permiten corregir el test teniendo en cuenta la edad y educación de la persona evaluada.(AU)

Introduction: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Test. The main purpose of the study is to provide an alternative version of the Stroop Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. Methods: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. Results: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; p < .001) and construct validity (r = 0.472-0.737; p < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12-40% of variance. Sex only had a significant effect on the resistance to interference index. Conclusions: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.(AU)

UD Interference Test: creation and validation of a new instrument of resistance to interference. Normalisation and standardisation for Spanish population.

INTRODUCTION: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Color and Word Test. The main purpose of the study is to provide an alternative version of the Stroop Color and Word Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. METHODS: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. RESULTS: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; P < .001) and construct validity (r = 0.472-0.737; P < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12% to 40% of variance. Sex only had a significant effect on the resistance to interference index. CONCLUSIONS: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.

Test breve de memoria visuoespacial-revisado: normalización y estandarización de la prueba en población española / Brief visuospatial memory test-revised (BVMT-R): normalization and standardization for Spanish population

Introducción: El test breve de memoria visuoespacial-revisado (BVMT-R) evalúa el aprendizaje y la memoria visuoespacial en población adulta. Este test cuenta con versiones paralelas que permiten su readministración.Objetivo: Obtener datos normativos y estandarizados para el BVMT-R adecuados a las características sociodemográficas de la población española.Sujetos y métodos: El estudio se enmarca dentro del proyecto Normacog. Se evaluó a 903 participantes (rango de edad: 18-93 años) con el BVMT-R (versión 1). Se analizaron el efecto de la edad, el nivel educativo y el sexo sobre el BVMT-R, y se crearon los percentiles y las puntuaciones escalares ajustadas por edad y nivel educativo. Resultados: Se observó un efecto significativo de la edad y el nivel educativo sobre todas las variables analizadas (ensayo 1, recuerdo total, ensayo 4 e índice de discriminación), que explica entre el 12 y el 40% de la varianza. Los participantes más mayores y con menor nivel educativo obtuvieron un menor rendimiento en el BVMT-R. El sexo no presentó un efecto significativo en las variables analizadas. Conclusión: Este estudio aporta baremos estandarizados y normalizados para el BVMT-R, teniendo en cuenta las características sociodemográficas de la población española. Los resultados confirman la influencia de la edad y la educación en el rendimiento del test, por lo que aportamos datos que permiten corregir el BVMT-R teniendo en cuenta dichas características.(AU)

Introduction: The brief visuospatial memory test-revised (BVMT-R) assesses visuospatial learning and memory in adults. It has equivalent forms that allow reassessing patients. Aim: To obtain normative and standardized data for the BVMT-R taking into account the sociodemographic characteristics of the Spanish population.Subjects and methods: The present study is part of the Normacog Project. Nine hundred three participants (18 to 93 years old) were assessed using the BVMT-R (form 1). The effect of age, level of education and gender was analyzed on the BVMT-R, and percentiles and scalar scores adjusted by age and level of education were created.Results: A significant effect of age and educational level on the analyzed variables was observed (trial 1; total recall; trial 4; discrimination index), explaining from 12% to 40% of the variance. The older and less educated participants obtained lower performance in all the analyzed variables of the BVMT-R. Gender had not a significant effect in the analyzed variables.Conclusion: The study provides standardized and normalized data for the BVMT-R taking into account the Spanish sociodemographic characteristics. The results confirm the influence of age and level of education in the performance of the test, so normative data are provided to correct the BVMT-R taking into account these characteristics.(AU)

[Brief visuospatial memory test-revised (BVMT-R): normalization and standardization for Spanish population]. / Test breve de memoria visuoespacial-revisado: normalización y estandarización de la prueba en población española.

INTRODUCTION: The brief visuospatial memory test-revised (BVMT-R) assesses visuospatial learning and memory in adults. It has equivalent forms that allow reassessing patients. AIM: To obtain normative and standardized data for the BVMT-R taking into account the sociodemographic characteristics of the Spanish population. SUBJECTS AND METHODS: The present study is part of the Normacog Project. Nine hundred three participants (18 to 93 years old) were assessed using the BVMT-R (form 1). The effect of age, level of education and gender was analyzed on the BVMT-R, and percentiles and scalar scores adjusted by age and level of education were created. RESULTS: A significant effect of age and educational level on the analyzed variables was observed (trial 1; total recall; trial 4; discrimination index), explaining from 12% to 40% of the variance. The older and less educated participants obtained lower performance in all the analyzed variables of the BVMT-R. Gender had not a significant effect in the analyzed variables. CONCLUSION: The study provides standardized and normalized data for the BVMT-R taking into account the Spanish sociodemographic characteristics. The results confirm the in?uence of age and level of education in the performance of the test, so normative data are provided to correct the BVMT-R taking into account these characteristics.

TITLE: Test breve de memoria visuoespacial-revisado: normalización y estandarización de la prueba en población española.Introducción. El test breve de memoria visuoespacial-revisado (BVMT-R) evalúa el aprendizaje y la memoria visuoespacial en población adulta. Este test cuenta con versiones paralelas que permiten su readministración. Objetivo. Obtener datos normativos y estandarizados para el BVMT-R adecuados a las características sociodemográficas de la población española. Sujetos y métodos. El estudio se enmarca dentro del proyecto Normacog. Se evaluó a 903 participantes (rango de edad: 18-93 años) con el BVMT-R (versión 1). Se analizaron el efecto de la edad, el nivel educativo y el sexo sobre el BVMT-R, y se crearon los percentiles y las puntuaciones escalares ajustadas por edad y nivel educativo. Resultados. Se observó un efecto significativo de la edad y el nivel educativo sobre todas las variables analizadas (ensayo 1, recuerdo total, ensayo 4 e índice de discriminación), que explica entre el 12 y el 40% de la varianza. Los participantes más mayores y con menor nivel educativo obtuvieron un menor rendimiento en el BVMT-R. El sexo no presentó un efecto significativo en las variables analizadas. Conclusión. Este estudio aporta baremos estandarizados y normalizados para el BVMT-R, teniendo en cuenta las características sociodemográficas de la población española. Los resultados confirman la influencia de la edad y la educación en el rendimiento del test, por lo que aportamos datos que permiten corregir el BVMT-R teniendo en cuenta dichas características.

UD Interference Test: Creation and validation of a new instrument of resistance to interference. Normalization and standardization for Spanish population. / Test UD Interferencia: Creación y validación de un nuevo instrumento de resistencia a la interferencia. Normalización y estandarización en población española.

INTRODUCTION: The UD Interference Test measures processing speed and attention, and is based on the concept of interference of the Stroop Test. The main purpose of the study is to provide an alternative version of the Stroop Test that overcomes some of the limitations of previous versions in assessing individuals with daltonism or age-related reading difficulties, and to obtain normative and standardised data for the Spanish population. METHODS: This study is part of the Normacog project. We evaluated 905 individuals (age range, 18-93 years) to analyse the test's reliability and concurrent and construct validity. We evaluated the effect of age, sex, and level of education on UD Interference Test performance and calculated percentiles and age- and education-adjusted scaled scores. RESULTS: The test has good reliability (α = 0.875) and concurrent (r = 0.443-0.725; p < .001) and construct validity (r = 0.472-0.737; p < .001). We observed age and educational level to have a significant effect on UD Interference Test scores, explaining 12-40% of variance. Sex only had a significant effect on the resistance to interference index. CONCLUSIONS: We present an alternative version of the Stroop Color and Word Test with some advantages over previous versions. We provide standardised and normalised data for the Spanish population to correct the test according to the subject's age and level of education.

[Hopkins Verbal Learning Test-revised: normalization and standardization for Spanish population]. / Test de aprendizaje verbal de Hopkins revisado: normalización y estandarización de la prueba en población española.

INTRODUCTION: The Hopkins Verbal Learning Test-revised (HVLT-R) was originally created with the objective of providing a short verbal memory and learning test with six alternative forms that allow the re-administration. AIM: To obtain normative and standardized data for the HVLT-R taking into account the sociodemographic characteristics of the current Spanish population. SUBJECTS AND METHODS: The study is part of the Normacog Project. Seven hundred participants (18 to 90 years old) were assessed. The effect of age, level of education and gender on the performance of HVLT-R were analyzed, and percentiles and scalar scores adjusted by age and level of education were created. RESULTS: A significant effect of age and educational level on the analyzed variables of the test was observed, explaining from 15% to 29% of the variance (trial 1, total recall, trial 4, discrimination index). As expected, the older and less educated obtained lower performance in all the analyzed variables of the HVLT-R. However, sex only had a significant effect on the variables trial 1, total recall and discrimination index. CONCLUSION: This study provides standardized and normalized data for the HVLT-R for the Spanish population, offering current norms to clinicians and researchers. The results confirm the influence of age and level of education on all the indicators of the test, so normative data are provided to correct the HVLT-R taking into account these characteristics.

TITLE: Test de aprendizaje verbal de Hopkins revisado: normalización y estandarización de la prueba en población española.Introducción. El test de aprendizaje verbal de Hopkins revisado (HVLT-R) se creó originalmente con el objetivo de proporcionar un test de aprendizaje y memoria verbal corto y con seis versiones paralelas que permitieran su readministración. Objetivo. Obtener datos normativos y estandarizados para el HVLT-R adaptado a las características sociodemográficas de la población española actual. Sujetos y métodos. El estudio se enmarca dentro del proyecto Normacog, para el cual se evaluó a 700 participantes (rango de edad: 18-90 años). Se analizó el efecto de la edad, el nivel educativo y el sexo sobre el rendimiento del HVLT-R, y se crearon los percentiles y las puntuaciones escalares ajustadas por edad y nivel educativo. Resultados. Se observó un efecto significativo de la edad y el nivel educativo sobre las variables analizadas del test, que explicaba entre el 15 y el 29% de la varianza (ensayo 1, recuerdo total, ensayo 4, índice de discriminación). Como era de esperar, a mayor edad y menor nivel educativo, el rendimiento en el HVLT-R fue menor en todas las variables analizadas. Sin embargo, el sexo presentó un efecto significativo únicamente en las variables ensayo 1, recuerdo total e índice de discriminación. Conclusión. Este estudio presenta baremos estandarizados y normalizados para el HVLT-R para población española, y ofrece normas actuales para los clínicos e investigadores. Los resultados confirman la influencia de la edad y la educación en todos los indicadores del test, por lo que se aportan datos que permiten corregir el HVLT-R teniendo en cuenta dichas características.

[Montreal Cognitive Assessment Test: normalization and standardization for Spanish population]. / Test de evaluacion cognitiva de Montreal: normalizacion y estandarizacion de la prueba en poblacion española.

INTRODUCTION: The Montreal Cognitive Assessment (MoCA) is a brief screening test that assesses the general cognitive state. It has become very popular and useful as an alternative resource for the traditional Mini-Mental State Examination. AIM: To normalize and to standardize the MoCA taking into account the sociodemographic characteristics of the Spanish population (INE data, 2012). SUBJECTS AND METHODS: The present study is part of the Normacog Project. Seven hundred participants were recruited (older than 18 years old). The effect of age, level of education and sex was analyzed on the performance of MoCA and percentiles and scalar score for nine ranges of age and scalar score adjusted by the level of education. RESULTS: Results showed a significant effect of age, level of education and sex on the cognitive performance of MoCA. However, sex was only significant in two domains (attention and delayed recall). Age, education and sex explained from 1.0% to 32.3% of the variance of the performance. The older participants with lower level of formal education obtained the worse performance shown in MoCA. Percentiles and scalar score for each range of age, and scalar score adjusted by the level of education were obtained. CONCLUSION: The normative data of the MoCA is provided taking into account the Spanish sociodemographic characteristics for adults in Spain and the cut-off to distinguish between normal cognitive performance and mild cognitive impairment according to different range of ages have been proposed.

TITLE: Test de evaluacion cognitiva de Montreal: normalizacion y estandarizacion de la prueba en poblacion española.Introduccion. La evaluacion cognitiva de Montreal (MoCA) es un test de cribado breve que evalua el estado cognitivo general, y resulta un recurso alternativo, muy util, al tradicional test minimental. Objetivo. Normalizar y estandarizar el test MoCA, teniendo en cuenta las caracteristicas sociodemograficas de la poblacion española (datos INE, 2012). Sujetos y metodos. El estudio se enmarca dentro del proyecto Normacog, en el que se evaluo a 700 participantes (18-86 años). Se analizaron el efecto de la edad, el nivel educativo y el sexo sobre el rendimiento del test MoCA, y se crearon los percentiles, las puntuaciones escalares para nueve rangos de edad y la puntuacion escalar normalizada ajustada por edad y nivel educativo. Resultados. Los resultados mostraron un efecto significativo de la edad, el nivel educativo y el sexo sobre el rendimiento cognitivo en el test MoCA. Sin embargo, el sexo solo presento un efecto significativo sobre dos dominios cognitivos: atencion y recuerdo diferido. La edad, la educacion y el sexo explicaron entre el 1% y el 32,3% de la varianza en las variables analizadas del test. Los participantes mas mayores con menor nivel de educacion formal obtuvieron peor rendimiento cognitivo. Se obtuvieron los percentiles y las puntuaciones escalares para cada rango de edad y la puntuacion escalar normalizada individual. Conclusion. Se presentan los datos normativos del test MoCA adecuados a las caracteristicas sociodemograficas de la sociedad española y los puntos de corte propuestos para discriminar entre rendimiento cognitivo normal y deterioro cognitivo leve segun los diferentes rangos de edad.

Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium.

Cognitive impairment is a key feature of schizophrenia (SZ) and determines functional outcome. Nonetheless, molecular signatures in neuronal tissues that associate with deficits are not well understood. We conducted nasal biopsy to obtain olfactory epithelium from patients with SZ and control subjects. The neural layers from the biopsied epithelium were enriched by laser-captured microdissection. We then performed an unbiased microarray expression study and implemented a systematic neuropsychological assessment on the same participants. The differentially regulated genes in SZ were further filtered based on correlation with neuropsychological traits. This strategy identified the SMAD 5 gene, and real-time quantitative PCR analysis also supports downregulation of the SMAD pathway in SZ. The SMAD pathway has been important in multiple tissues, including the role for neurodevelopment and bone formation. Here the involvement of the pathway in adult brain function is suggested. This exploratory study establishes a strategy to better identify neuronal molecular signatures that are potentially associated with mental illness and cognitive deficits. We propose that the SMAD pathway may be a novel target in addressing cognitive deficit of SZ in future studies.

In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.

Decoupling of N-acetyl-aspartate and glutamate within the dorsolateral prefrontal cortex in schizophrenia.

Aberrant function of glutamatergic pathways is likely to underlie the pathology of schizophrenia. Evidence of oxidative stress in the disease pathology has also been reported. N-Acetylaspartate (NAA) is metabolically linked to both cascades and may be a key marker in exploring the interconnection of glutamatergic pathways and oxidative stress. Several studies have reported positive correlation between the levels of NAA and Glx (the sum of glutamate and glutamine) in several brain regions in healthy subjects, by using proton magnetic resonance spectroscopy ([(1)H]MRS). Interestingly, one research group recently reported decoupling of the relationship between NAA and Glx in the hippocampus of patients with schizophrenia. Here we report levels of NAA and Glx measured using [(1)H]MRS, relative to the level of creatine (Cr) as an internal control. The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in 25 patients with schizophrenia and 17 matched healthy controls were studied. In DLPFC, NAA/Cr and Glx/Cr were significantly positively correlated in healthy controls after correction for the effect of age and smoking status and after correction for multiple comparisons (r= 0.627, P= 0.017). However, in patients with schizophrenia, the positive correlation between NAA/Cr and Glx/Cr was not observed even after correcting for these two variables (r= -0.330, P= 0.124). Positive correlation between NAA/Cr and Glx/Cr was not observed in the ACC in both groups. Decoupling of NAA and Glx in the DLPFC may reflect the interconnection of glutamatergic pathways and oxidative stress in the pathology of schizophrenia, and may possibly be a biomarker of the disease.

Hierarchical structure of the cognitive processes in schizophrenia: the fundamental role of processing speed.

OBJECTIVE: Decreased processing speed (PS) is a key feature of schizophrenia with respect to cognition, functional outcome and clinical symptoms. Our objective was to test whether PS slowing mediates other neuropsychological deficits among patients with chronic schizophrenia. METHOD: One hundred patients with schizophrenia and 53 healthy adults completed a series of neuropsychological measures that assess six cognitive domains. In addition to PS these included attention, verbal memory, visual memory, working memory, and executive functioning. Confirmatory factor analysis (CFA) was used to evaluate the fit of the 6-factor model. The cognitive performances of both groups were compared before and after controlling for the effect of PS, but also after controlling for the effect of each cognitive factor at a time. Finally, the PS-related variance was removed and the effect of the other cognitive factors was tested again. RESULTS: CFA supported the hypothesized 6-factor cognitive structure. As expected, the patients and controls differed on all cognitive measures. However, after controlling for the effects of PS, group differences on the other five cognitive factors decreased substantially. Controlling for other factors produced smaller attenuation of group differences, and these effects were also partially accounted for by decreased PS. CONCLUSIONS: PS deficits account for most of the differences in cognition between patients with schizophrenia and healthy controls. PS slowing appears to be a core feature of schizophrenia, one that underlies impairments of working memory, executive functioning, and other abilities.

Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe.

The current model of fear conditioning suggests that it is mediated through modules involving the amygdala (AMY), hippocampus (HIP), and frontal lobe (FL). We now test the hypothesis that habituation and acquisition stages of a fear conditioning protocol are characterized by different event-related causal interactions (ERCs) within and between these modules. The protocol used the painful cutaneous laser as the unconditioned stimulus and ERC was estimated by analysis of local field potentials recorded through electrodes implanted for investigation of epilepsy. During the prestimulus interval of the habituation stage FL>AMY ERC interactions were common. For comparison, in the poststimulus interval of the habituation stage, only a subdivision of the FL (dorsolateral prefrontal cortex, dlPFC) still exerted the FL>AMY ERC interaction (dlFC>AMY). For a further comparison, during the poststimulus interval of the acquisition stage, the dlPFC>AMY interaction persisted and an AMY>FL interaction appeared. In addition to these ERC interactions between modules, the results also show ERC interactions within modules. During the poststimulus interval, HIP>HIP ERC interactions were more common during acquisition, and deep hippocampal contacts exerted causal interactions on superficial contacts, possibly explained by connectivity between the perihippocampal gyrus and the HIP. During the prestimulus interval of the habituation stage, AMY>AMY ERC interactions were commonly found, while interactions between the deep and superficial AMY (indirect pathway) were independent of intervals and stages. These results suggest that the network subserving fear includes distributed or widespread modules, some of which are themselves "local networks." ERC interactions between and within modules can be either static or change dynamically across intervals or stages of fear conditioning.

Painful laser stimuli induce directed functional interactions within and between the human amygdala and hippocampus.

The pathways by which painful stimuli are signaled within the human medial temporal lobe are unknown. Rodent studies have shown that nociceptive inputs are transmitted from the brainstem or thalamus through one of two pathways to the central nucleus of the amygdala. The indirect pathway projects from the basal and lateral nuclei of the amygdala to the central nucleus, while the direct pathway projects directly to the central nucleus. We now test the hypothesis that the human ventral amygdala (putative basal and lateral nuclei) exerts a causal influence upon the dorsal amygdala (putative central nucleus), during the application of a painful laser stimulus. Local field potentials (LFPs) were recorded from depth electrode contacts implanted in the medial temporal lobe for the treatment of epilepsy, and causal influences were analyzed by Granger causality (GRC). This analysis indicates that the dorsal amygdala exerts a pre-stimulus causal influence upon the hippocampus, consistent with an attention-related response to the painful laser. Within the amygdala, the analysis indicates that the ventral contacts exert a causal influence upon dorsal contacts, consistent with the human (putative) indirect pathway. Potentials evoked by the laser (LEPs) were not recorded in the ventral nuclei, but were recorded at dorsal amygdala contacts which were not preferentially those receiving causal influences from the ventral contacts. Therefore, it seems likely that the putative indirect pathway is associated with causal influences from the ventral to the dorsal amygdala, and is distinct from the human (putative) indirect pathway which mediates LEPs in the dorsal amygdala.

Serum uric acid and brain ischemia in normal elderly adults.

BACKGROUND: Uric acid (UA) has antioxidant properties yet when elevated is associated with vascular disease and stroke. Further, even high normal UA is associated with increased risk of mild cognitive dysfunction in elderly adults. METHOD: In this cross-sectional, observational study, we examined the relationship between serum UA and aggregate volume of white matter hyperintense (WMH) signals observed on proton density and T2-weighted brain MR images in a community sample of 177 adults ages 20 to 92. Using logistic regression, we tested whether participants with UA concentrations in the highest quartile of the sample--but still normal--would have increased WMH volumes. RESULTS: Compared with those with low to moderate levels, participants with high normal serum UA were more likely to fall in the highest quartile of WMH volume. The odds ratios (95% CIs) of increased WMH were 2.6 (1.2 to 5.4) for total, 2.5 (1.2 to 5.1) for periventricular, and 2.8 (1.4 to 5.9) for subcortical WMH volume. After controlling for age, sex, race, education, body mass, hypertension, and diabetes, the multivariate-adjusted odds of large total and subcortical WMH volumes remained elevated. Finally, high normal UA increased the odds of having excessive ischemic burden four- to fivefold in adults ages 60 and older. CONCLUSIONS: These findings demonstrate that mildly elevated serum uric acid is associated with increased burden of cerebral ischemic pathology, particularly in older adults. We outline the potential pathogenesis of this association. A clinical trial of antihyperuricemic medication to treat or prevent chronic brain ischemia might be warranted.

Determinants of Benton Facial Recognition Test performance in normal adults.

Clinical investigations have found that lesions of the right cerebral hemisphere can disrupt face perception. Much less is known about the determinants of facial discrimination in healthy adults, although age-related differences in many cognitive abilities have been shown to correlate with simple processing speed and variation in regional brain volumes. In this study, 174 healthy adults between the ages of 20 and 92 were asked to match pictures of unfamiliar faces. After their performance was regressed on age, sex, education, and perceptual comparison speed, adding terms for frontal lobe volume, nonfrontal volume, and ventricle-to-brain ratio (VBR) derived from magnetic resonance imaging improved the model and accounted for 35% of the variance in facial discrimination. VBR and processing speed alone accounted for nearly 34% of the variance. These findings suggest that both normal atrophic brain changes and decreases in processing speed contribute to individual differences in facial discrimination.

Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency.

Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involves the nearly complete absence of an enzyme (hypoxanthine-guanine phosphoribosyltransferase, or HPRT) that is essential for purine salvage. In addition to hyperuricemia, all patients with classic LND suffer from movement disorder and compulsive self-injury, and most have mental retardation. Patients with partial HPRT deficiency (variants) always have hyperuricemia and often have neurologic abnormalities, but do not self-injure and usually are described as having normal intelligence. Here we compare 15 patients with LND to 9 variants and 13 normal adolescents and adults. Testing revealed unambiguous and qualitatively similar cognitive deficits in both patient groups. The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND.

Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid-spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal-executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal-executive theory of cognitive aging are partially correct and complement one another.

Demographic, clinical, and neurocognitive correlates of everyday functional impairment in severe mental illness.

Although cognitive deficits often accompany severe mental illness, their implications for everyday functioning remain poorly understood. In this study, an occupational therapist (OT) rated the everyday functioning of 105 adult psychiatric patients. Using demographic, clinical, and cognitive variables, the authors tested alternative models to account for the observed variability in OT ratings. Although age, education, and the presence of schizophrenia each contributed to a model that accounted for 27% of the variation in functional independence, adding terms for auditory divided attention and verbal learning increased the proportion of explained variance to 45% and decreased the beta weights for age and education--but not schizophrenia--to nonsignificant levels. These findings demonstrate the relevance of cognitive performance to everyday functioning in severe mental illness. They are discussed with respect to hypothesized determinants of psychiatric disability.

Construct and concurrent validity of the Hopkins Verbal Learning Test-revised.

The present investigation examined the validity of the revised Hopkins Verbal Learning Test (HVLT-R). In a principal components analysis with varimax rotation, measures of new learning and delayed recall loaded on a single factor distinguishable from measures related to general cognitive function and visual memory. The HVLT-R also correlated most strongly with other tests of verbal memory and relatively weakly with a test of general intelligence. Group comparisons showed that normal controls performed better than age- and education-matched patients with probable Alzheimer's disease (AD) or vascular dementia (VaD). Discriminant function analyses and Bayesian statistics revealed high classification accuracies for dementia patients versus controls. When scores on the HVLT-R and other neuropsychological tests were subjected to discriminant function analyses, performance on the HVLT-R delayed recognition task was found to be the most useful in discriminating patients with AD from those with VaD. We conclude that the HVLT-R is a valid test of verbal learning and memory that is best suited for use with elderly patients suspected of dementia.