Heritability of semantic verbal fluency task using time-interval analysis.

Individual variability in word generation is a product of genetic and environmental influences. The genetic effects on semantic verbal fluency were estimated in 1,735 participants from the Brazilian Baependi Heart Study. The numbers of exemplars produced in 60 s were broken down into time quartiles because of the involvement of different cognitive processes-predominantly automatic at the beginning, controlled/executive at the end. Heritability in the unadjusted model for the 60-s measure was 0.32. The best-fit model contained age, sex, years of schooling, and time of day as covariates, giving a heritability of 0.21. Schooling had the highest moderating effect. The highest heritability (0.17) was observed in the first quartile, decreasing to 0.09, 0.12, and 0.0003 in the following ones. Heritability for average production starting point (intercept) was 0.18, indicating genetic influences for automatic cognitive processes. Production decay (slope), indicative of controlled processes, was not significant. The genetic influence on different quartiles of the semantic verbal fluency test could potentially be exploited in clinical practice and genome-wide association studies.

Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load.

Cardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50-85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.

Acute effects of donepezil in healthy young adults underline the fractionation of executive functioning.

The cholinergic system is involved in the modulation of both bottom-up and top-down attentional control. Top-down attention engages multiple executive control processes, but few studies have investigated whether all or selective elements of executive functions are modulated by the cholinergic system. To investigate the acute effects of the pro-cholinergic donepezil in young, healthy volunteers on distinct components of executive functions we conducted a double-blind, placebo-controlled, independent-groups design study including 42 young healthy male participants who were randomly assigned to one of three oral treatments: glucose (placebo), donepezil 5 mg or donepezil 7.5 mg. The test battery included measures of different executive components (shifting, updating, inhibition, dual-task performance, planning, access to long-term memory), tasks that evaluated arousal/vigilance/visuomotor performance, as well as functioning of working memory subsidiary systems. Donepezil improved sustained attention, reaction times, dual-task performance and the executive component of digit span. The positive effects in these executive tasks did not correlate with arousal/visuomotor/vigilance measures. Among the various executive domains investigated donepezil selectively increased dual-task performance in a manner that could not be ascribed to improvement in arousal/vigilance/visuomotor performance nor working memory slave systems. Other executive tasks that rely heavily on visuospatial processing may also be modulated by the cholinergic system.

The Prospective and Retrospective Memory Questionnaire: a population-based random sampling study.

The Prospective and Retrospective Memory Questionnaire (PRMQ) has been shown to have acceptable reliability and factorial, predictive, and concurrent validity. However, the PRMQ has never been administered to a probability sample survey representative of all ages in adulthood, nor have previous studies controlled for factors that are known to influence metamemory, such as affective status. Here, the PRMQ was applied in a survey adopting a probabilistic three-stage cluster sample representative of the population of Sao Paulo, Brazil, according to gender, age (20-80 years), and economic status (n=1042). After excluding participants who had conditions that impair memory (depression, anxiety, used psychotropics, and/or had neurological/psychiatric disorders), in the remaining 664 individuals we (a) used confirmatory factor analyses to test competing models of the latent structure of the PRMQ, and (b) studied effects of gender, age, schooling, and economic status on prospective and retrospective memory complaints. The model with the best fit confirmed the same tripartite structure (general memory factor and two orthogonal prospective and retrospective memory factors) previously reported. Women complained more of general memory slips, especially those in the first 5 years after menopause, and there were more complaints of prospective than retrospective memory, except in participants with lower family income.

Effects of lorazepam on visual perceptual abilities.

OBJECTIVE: To evaluate the effects of an acute dose of the benzodiazepine (BZ) lorazepam in young healthy volunteers on five distinguishable visual perception abilities determined by previous factor-analytic studies. METHODS: This was a double-blind, cross-over design study of acute oral doses of lorazepam (2 mg) and placebo in young healthy volunteers. We focused on a set of paper-and-pencil tests of visual perceptual abilities that load on five correlated but distinguishable factors (Spatial Visualization, Spatial Relations, Perceptual Speed, Closure Speed, and Closure Flexibility). Some other tests (DSST, immediate and delayed recall of prose; measures of subjective mood alterations) were used to control for the classic BZ-induced effects. RESULTS: Lorazepam impaired performance in the DSST and delayed recall of prose, increased subjective sedation and impaired tasks of all abilities except Spatial Visualization and Closure Speed. Only impairment in Perceptual Speed (Identical Pictures task) and delayed recall of prose were not explained by sedation. CONCLUSION: Acute administration of lorazepam, in a dose that impaired episodic memory, selectively affected different visual perceptual abilities before and after controlling for sedation. Central executive demands and sedation did not account for results, so impairment in the Identical Pictures task may be attributed to lorazepam's visual processing alterations.

Sleep habits and complaints of adults in the city of São Paulo, Brazil, in 1987 and 1995.

This study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995. Representative samples of 1000 adult residents per survey were interviewed using a validated structured sleep questionnaire, the "UNIFESP Sleep Questionnaire". Difficulty maintaining sleep, difficulty initiating sleep and early morning awakening, occurring at least three times a week, were reported in 1987 and 1995, by 15.8/27.6, 13.9/19.1, and 10.6/14.2% of the interviewees, respectively, significantly increasing throughout time. These sleep problems were more often found among women. Frequencies of excessive diurnal sleepiness and sleep attacks were unchanged comparing 1987 with 1995 (4.5 vs 3.8 and 3.1 vs 3.0%, respectively). Parasomnia complaints remained unchanged, with the exception of leg cramps, which doubled in prevalence from 1987 to 1995 (2.6 to 5.8%). Snoring was the most common parasomnia (21.5% in 1995), reported more often by men than by women, and somnambulism was the least common (approximately 1%). Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. Approximately 12% of the subjects in both surveys had consulted a physician due to sleep problems and 3.0% reported habitual use of sleep-promoting substances in 1995. Overall, there was a significant increase in insomnia complaints from 1987 to 1995 in the general population of the city of São Paulo. This major change over a little under a decade should be considered as an important public health issue.

Effects of lorazepam on deductive reasoning.

RATIONALE: Benzodiazepines slow reasoning performance, but it is still unknown which phase of reasoning is affected and whether this effect is present for different types of relations between entities in reasoning problems. OBJECTIVES: We investigated which phases of deductive reasoning are affected by lorazepam and whether this effect varies according to the type of relations in deductive reasoning problems. METHODS: This was a double-blind, crossover design study of acute oral doses of lorazepam (2 mg) and placebo, using young healthy volunteers. We focused on response delay of three separable phases of deductive reasoning and matched working memory tasks (that involved only maintenance of information) the premise processing phase, the premise integration phase, and the validation phase, in which reasoners decide whether a conclusion logically follows from the premises (reasoning task) or is identical to one of the premises (maintenance task). Type of relations in the premises was also manipulated. We employed material that was difficult to envisage visually and visuospatially ("subiconic") and material easy to envisage visually or visuospatially. RESULTS: Lorazepam slowed response as memory load increased, irrespective of type of relations. It also specifically slowed validation in reasoning problems with visual relations, an effect that disappeared after subtraction of maintenance scores, and increased validation time in problems with subiconic relations, which remained after this subtraction. CONCLUSION: Acute lorazepam administration affected reasoning in two ways: it slowed processing nonspecifically when working memory demands increased and augmented validation time depending on the difficulty in generating and/or manipulating mental representations by the central executive.

Zolpidem and memory: a study using the process-dissociation procedure.

RATIONALE: There is a dearth of studies which have employed sophisticated paradigms to investigate the effects of zolpidem on memory. OBJECTIVES: To explore anterograde cognitive deficits induced by acute oral doses of zolpidem by means of the process-dissociation procedure (PDP). METHODS: The present study followed a placebo-controlled, double-blind, parallel-group design. Young, healthy females were randomly allocated to one of three treatments with 12 subjects each: placebo, 5 mg and 10 mg zolpidem. Two word-stem completion tasks were carried out close to theoretical peak-plasma concentration: a) direct inclusion task with cued recall, in which participants had to try to use words seen at study to complete stems; and b) direct exclusion task, in which words seen at study were to be avoided as completions. The PDP was applied to the results in these tasks to yield indices of explicit/controlled (C) and implicit/automatic (A) memory. Classical psychometric tests were also carried out. RESULTS: Zolpidem 10 mg led to cognitive effects similar to benzodiazepines (except for the atypical lorazepam), including impairment of exclusion, but not inclusion-task performance. Results of the application of the PDP were inconclusive but concurred with the pattern established in previously published work on benzodiazepine effects, i.e. that zolpidem (10 mg) impaired C. CONCLUSIONS: Zolpidem leads to cognitive effects similar to most benzodiazepines. Although the application of PDP in drug studies may be counterproductive in view of methodological difficulties that are discussed, the pattern of effects on the stem-completion tasks involved in this paradigm is potentially useful in the investigation of cognitive effects of psychoactive drugs.

Stem-completion tasks (indirect, direct inclusion and exclusion) are differently affected by equipotent doses of lorazepam and flunitrazepam.

This study was designed to explore the effects on performance in stem-completion tasks of two benzodiazepines (BZ) in equipotent doses: lorazepam, a drug that atypically disrupts perceptual priming, and flunitrazepam, a compound with standard BZ effects. The study followed a placebo-controlled, double-blind, parallel-group design. Thirty-six young and healthy subjects carried out three completion tasks at theoretical peak-plasma concentrations of drugs: (a) indirect tasks, in which the subjects were instructed to complete stems with the first word that came to mind; (b) direct inclusion tasks/cued recall, in which the participants had to try to use words seen at study as completions; and (c) direct exclusion tasks, in which words seen at study were to be avoided. The PDP was applied to the results in the inclusion and exclusion tasks, to obtain indices of explicit/controlled (C) and implicit/automatic (A) memory. The C index was lowered by both BZs and A was equivalent in all treatments, confirming the general amnestic action of BZs. However, lorazepam led to decreases in completions in the indirect and inclusion tasks, while flunitrazepam impaired performance in the exclusion task. The qualitative differences between the drugs in their effects on performance suggest that these BZs may lead to differences in response bias.

Lorazepam induces an atypical dissociation of visual and auditory event-related potentials.

Lorazepam has been reported to atypically disrupt visual processing compared to other benzodiazepines (BZs), but it is not known to what extent this effect extends to impairment in other modalities. Our objective was to compare the effects of lorazepam with those of flunitrazepam, a BZ with standard effects, on visual and auditory event-related potentials (ERPs) using the same paradigm. The study followed a placebo-controlled, double-blind, parallel group-design and involved single oral doses of lorazepam (2.0 mg), flunitrazepam (1.2 mg) and placebo. Thirty-six young, healthy subjects completed a test battery before and after treatment including classic behavioural tests, visual and auditory ERPs. Both drugs led to comparable alterations on behavioural tests and double-dissociations were found, indicating that the doses used were equipotent: lorazepam was more deleterious than flunitrazepam and placebo in fragmented shape identification, while simple reaction times were prolonged for flunitrazepam in comparison to lorazepam and placebo. Effects on P3 latencies were also distinct: alterations in both modalities for flunitrazepam were equivalent and greater than placebo's. In contrast, lorazepam at the frontal and central electrode sites led to greater changes in visual than in auditory latency, and also to longer visual latencies than flunitrazepam and placebo, but lorazepam's auditory latency effects were only different to placebo's at the parietal electrode site. Peripheral visual changes were not responsible for these effects. Differences in the impairment profile between equipotent doses of lorazepam and flunitrazepam suggests that lorazepam induces atypical central visual processing changes.

Verbal fluency facilitated by the cholinergic blocker, scopolamine.

This study was designed to explore putative facilitatory effects of low doses of scopolamine (SP) on phonemic (letter) and semantic (category) verbal fluency. A double-blind, parallel-group design was used with 36 subjects who completed a test battery before and 2 h after 0.6 mg or 1.2 mg of SP or placebo. Fluency measures included total number of words generated, clustering (the production of words within semantic or phonemic subcategories) and switching (the ability to shift efficiently to new subcategories). Low doses of scopolamine increased phonemic fluency, as has been shown previously. Semantic fluency was not increased by SP, although subjects treated with 1.2 mg of SP generated higher-frequency words. SP did not affect clustering or switching. It is suggested that phonemic and semantic fluency reflect distinct cognitive processes.

A set of 400 pictures standardised for Portuguese: norms for name agreement, familiarity and visual complexity for children and adults.

The present article provides normative measures for 400 pictured objects (Cycowicz et al., 1997) viewed by Portuguese speaking Brazilian University students and 5-7 year-old children. Name agreement, familiarity and visual complexity ratings were obtained. These variables have been shown to be important for the selection of adequate stimuli for cognitive studies. Children's name agreement was lower than that of adults. The children also failed to provide adequate modal names for 103 concepts, rated drawings as less familiar and less complex, and chose shorter names for pictures. The differences in ratings between adults and children were higher than those observed in the literature employing smaller picture sets. The pattern of correlations among measures observed in the present study was consistent with previous reports, supporting the usefulness of the 400 picture set as a tool for cognitive research in different cultures and ages.

A double-dissociation of behavioural and event-related potential effects of two benzodiazepines with similar potencies.

This study was designed to explore the role of benzodiazepine affinity to benzodiazepine binding site on acute psychomotor, subjective and memory effects, as well as auditory Event Related Potential (ERP) latencies, in healthy volunteers. Two benzodiazepines with similar affinity to benzodiazepine binding sites, or potency, were compared: the atypical compound lorazepam (2.0 mg), which has been reported to impair priming, and a standard benzodiazepine, flunitrazepam (0.6 mg, 0.8 mg, 1.0 mg). The study followed a placebo-controlled, double-blind, parallel-group design. Sixty subjects completed a test battery before treatment and at theoretical peak plasma concentration of drugs. Lorazepam and 1.0 mg of flunitrazepam led to comparable alterations on psychomotor, subjective and auditory episodic memory measures. A double-dissociation was found for lorazepam and the equipotent dose of flunitrazepam (1.0 mg): lorazepam was more deleterious than flunitrazepam in time taken to identify fragmented shapes. Lorazepam also impaired direct and indirect stem-completion in comparison to placebo, but this effect was abolished when time to identify shapes was used as a covariate. By contrast, 1.0 mg of flunitrazepam prolonged auditory ERP latencies to a greater extent than lorazepam. High affinity to the benzodiazepine binding sites does not seem to explain the consistent lorazepam-induced impairment of indirect stem-completion. Differences in impairment profile between the benzodiazepines employed may relate to the modality (visual or not) of the tasks used.

Sistema para análise simultânea de quatro potenciais evocados visuais multicanais utilizando equipamento comercial e processamento off-line / A system for the simultaneous analysis of four multichannel visual evoked potentials using a commercial equipment and off line processing

Numa proposta de pesquisa para estudar os correlatos eletrofisiológicos de processamento semântico de palavras apresentadas visualmente pretendia-se captar (e processar) quatro potenciais evocados cerebrais de algumas derivações num mesmo experimento, utilizando um equipamento comercial usado em centros hospitalares. Para viabilizar tal pesquisa, foi criado um protocolo especial, em que duas respostas visuais evocadas seqüencialmente, com uma latência de 4,15 s, eram adquiridas em uma mesma janela de aquisição. Como a taxa de amostragem resultante no equipamento foi adequada para a aplicação (100 Hz), foi possível realizar o experimento no próprio centro hospitalar, utilizando um equipamento com o qual os pesquisadores da área biomédica estavam bem familiarizados. Um problema adicional surgiu no tocante a artefatos por movimentação ocular. Este foi sanado graças à possibilidade de serem arquivadas todas as respostas individuais, e não somente a média coerente. Um algoritmo simples realizou a detecção de artefatos de forma eficiente. As soluções encontradas possibilitaram a realização da pesquisa proposta, sendo que essas mesmas soluções poderão permitir trabalhos em outros centos que se deparem com uma problemática semelhante à descrita.

Preliminary adaptation into Portuguese of a standardised picture set for the use in research and neuropsychological assessment.

Pictorial stimuli and words have been widely used to evaluate mnemonic processes in clinical settings, neuropsychological investigations, as well as in studies on the mechanisms underlying the phenomena of memory. However, there seem to be few studies of standardisation of pictures for research in this field. The present paper aimed at adapting the use of a set of pictures standardised for English speaking subjects for Portuguese speakers. Name agreement of 150 pictures was assessed in 100 high-school students. Ninety pictures were found to present the same name for over 90 subjects. Results yield data that may help create more controlled tests for the study of memory for pictorial stimuli in Brazil.

Benzodiazepine effects on memory tests: dependence on retrieval cues?

Acute effects of oral flunitrazepam (0.5 and 1 mg), nitrazepam (5 and 10 mg) and placebo were assessed on direct (free recall of words and prose, stem-cued recall) and indirect (stem and fragment completion) memory tasks. Fifty health volunteers took part in this double-blind, independent group study. The relative effects of the two benzodiazepines (BZs) on memory revealed a different pattern from their effects on alertness, indicating that their amnesic effects are not totally secondary to their sedative effects. The higher dose of flunitrazepam impaired free recall of words and prose but not cued recall, while neither drug affected the two indirect tasks. Differences in drug effects on the direct and indirect memory tasks were discussed in terms of resource demands of the various tests. We conclude that whether BZs impair performance on memory tasks depends more on the cues given at retrieval than the retrieval instructions (direct/indirect). The implications for this in terms of BZ amnestic effects are drawn out for contextual encoding deficits induced by BZs.

Does potency determine amnestic effects of benzodiazepines? A dose-response comparison of flunitrazepam and nitrazepam.

This study was designed to explore whether differences in the psychomotor, subjective and memory effects of different benzodiazepines (BDZ) relate to differences in their potencies. Two BDZs with similar kinetics but different potencies were compared. Flunitrazepam (0.5 and 1.0mg, nitrazepam (5 and 10mg) or placebo were administered to 50 healthy volunteers in a double-blind, parallel group design. Subjects completed a test battery before and 1.5h post-treatment. The higher dose of the more potent BDZ, flunitrazepam, impaired episodic memory in relation to placebo. In contrast, differences in psychomotor and subjective effects between BDZ were less clear. We conclude that a main caveat to the conclusion that potency plays a role in determining BDZ amnestic effects is the possible contribution of sedation and differential task sensitivities to apparent differential effects of BDZ compounds.

Scores of Brazilian University students on the Beck Depression and the State Trait Anxiety Inventories.

The profiles of the Beck Depression Inventory and State-Trait Anxiety Inventory scores were obtained for a sample of Brazilian university students and compared with those of other studies. Subjects were 270 students from various universities in São Paulo, age 23.8 yr. (SD=6.7 yr.). The mean Beck score for the total sample was 8.5 (SD=7.0); according to the cut-off score of 16, 86.9% were considered normal, 7.5% had scores compatible with dysphoria, and 5.6% had scores indicative of depression. The mean State-Trait Anxiety score for the total sample was 40.7 (SD=8.6). Considering one standard deviation as the threshold point, 17.8% published data indicated that the Portugese versions of the questionnaires are equivalent to original versions.