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PubMed2006

A longitudinal study of neurocognitive function in individuals at-risk for psychosis.

INTRODUCTION: Clinically defined prodromal diagnostic criteria identify at-risk individuals with a 35-40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established. METHODS: A comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed. RESULTS: At-risk subjects performed more poorly than healthy subjects (t=2.93, P=0.01), but better than first episode subjects (t=4.72, p<0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N=11; z=-1.2), while those at-risk subjects who did not progress to psychosis (N=17) performed better (z=-0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis. CONCLUSION: Neurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.

Adolescent↗

PubMed1994

Analysis of adult age differences on the Raven's Advanced Progressive Matrices Test.

The purpose of this project was to examine the nature of performance, and specifically, age-related performance, on the Raven's Advanced Progressive Matrices (APM) Test (Raven, Court, & Raven, 1983). In the 1st of 2 studies, 2 tests presumed to measure each of 4 hypothesized components of the APM and 3 tests presumed to measure processing speed were presented to 165 young adults. On the basis of correlational and confirmatory analyses, 1 of the components was not included in Study 2. The 2nd study was designed to examine the influence of the 3 remaining components, processing speed, and working memory on the individual and age-related differences on the APM. Participants included 183 adults between the ages of 21 and 83. The results suggest that although all 3 components are important to performance on the APM, rule application tasks seem to hold the most promise in accounting for age-related variance on the APM.

Adult↗

PubMed2006

Mental performance in old age dependent on cortisol and genetic variance in the mineralocorticoid and glucocorticoid receptors.

Depression and cognitive decline have been associated with changes in circulating cortisol concentrations. Cortisol exerts its functions through mineralocorticoid (MR) and glucocorticoid (GR) receptors. However, data on the influence of variations in the MR and GR genes on depressive symptoms and cognitive functioning in older adults are scarce. Therefore, we explored the impact of MR-215G/C, MR-I180V, GR-ER22/23EK, GR-N363S, and GR-BclI polymorphisms on these end points in the population-based Leiden 85-plus Study. This prospective study includes 563 participants aged 85 years and older, with a mean follow-up of 4.2 years. In this study, high morning cortisol levels (per 1 SD cortisol) associated with impairments in global cognitive functioning (p=0.002) at baseline (age 85). These impairments were mainly attributable to lower attention (p=0.057) and slower processing speed (p=0.014). Similar effects were also observed during follow-up (age 85-90), where participants with higher cortisol levels (per 1 SD cortisol) had impaired global cognitive functioning (p=0.003), as well as impairments in attention (p=0.034) and processing speed (p=0.013). Changes in depressive symptoms were observed for the MR-I180V single-nucleotide polymorphism (SNP), where during follow-up the prevalence of depressive symptoms was higher in the 180V-allele carriers (p=0.049) compared to noncarriers. Dependent on these polymorphisms, no differences in overall and in specific domains of cognitive functioning were observed. In conclusion, the MR-I180V SNP has a specific effect on depressive symptoms, independent from cognitive functioning, and other polymorphisms in the MR and GR genes. In contrast, these genetic variants in the MR and GR genes do not influence cognitive functioning in old age.

Aged, 80 and over↗

PubMed2005

Neuropsychological profile following suicide attempt by hanging: two adolescent case reports.

Hippocampal damage and amnesia following hypoxia and ischemia are described in the few published adult cases of suicide attempt by hanging. However, a recent review (Caine & Watson, 2000) suggests a variable pattern of brain involvement and neuropsychological impairments following hypoxic-ischemic injury that may or may not involve amnesia. To help clarify the impact of hanging on the developing brain, we examined neuropsychological functioning in two adolescents who survived suicide attempt by hanging. Despite differences in Glasgow Coma Scale (GCS), coma duration, and structural imaging findings, both patients had similar IQ (VIQ>PIQ) and presented with various combinations of deficits in expressive/receptive language, visual-constructional and perceptual ability, processing speed, attention, working memory, and/or executive functioning shortly after injury. In spite of their similarities, only one of the patients presented with classic amnesia symptoms in his early recovery. This patient was evaluated 1 year postinjury, and persistent deficits in processing speed and memory encoding were noted. Several hanging-related variables, including longer estimated hanging duration, greater weight, and severe airway edema, were thought to place this patient at increased risk for cognitive deficits. Clinical MRI scans of this patient obtained 6 weeks postinjury revealed mild volume loss as well as abnormalities in bilateral superior cortex. However, CT and MRI scans obtained throughout early recovery did not reveal overt evidence of injury to specific memory-related structures. Comprehensive neuropsychological evaluation of all adolescent survivors of suicide attempt by hanging is recommended, as a variety of postacute cognitive deficits were observed in these patients despite relatively short (<or=15 minutes) estimated hanging durations.

Adolescent↗

PubMed2001

Inhibitory control across the life span.

Findings from previous research suggest that inhibitory control improves during early childhood and declines during late adulthood. Very few researchers, however, have examined life-span changes in this ability in single studies. Within this life-span context, we investigated 1 type of inhibitory control--the ability to inhibit aprepotent response and generate an incompatible response--in individuals ranging from 6 to 82 years of age. Examination of raw reaction time data revealed a significantly larger inhibitory control effect for children and older adults than for young adults. Using proportional and z score transformations, we demonstrated that a processing speed explanation is sufficient to account for the differences in performance between children and young adults; this explanation, however, did not adequately explain the discrepancy between young and older adults. Taken together, these findings suggest that, above and beyond differences in processing speed, inhibitory control was less efficient in older adults. Our findings are consistent with the assertion that inhibitory control develops quite early and declines at the later end of the developmental spectrum.

Adolescent↗

PubMed2005

Attentional functions of parietal and frontal cortex.

A model of normal attentional function, based on the concept of competitive parallel processing, is used to compare attentional deficits following parietal and frontal lobe lesions. Measurements are obtained for visual processing speed, capacity of visual short-term memory (VSTM), spatial bias (bias to left or right hemifield) and top-down control (selective attention based on task relevance). The results show important differences, but also surprising similarities, in parietal and frontal lobe patients. For processing speed and VSTM, deficits are selectively associated with parietal lesions, in particular lesions of the temporoparietal junction. We discuss explanations based on either grey matter or white matter lesions. In striking contrast, measures of attentional weighting (spatial bias and top-down control) are predicted by simple lesion volume. We suggest that attentional weights reflect competition between broadly distributed object representations. Parietal and frontal mechanisms work together, both in weighting by location and weighting by task context.

Acoustic Stimulation↗

PubMed2005

A model of verbal memory impairments in schizophrenia: two systems and their associations with underlying cognitive processes and clinical symptoms.

BACKGROUND: In a broad cognitive study of schizophrenia we investigated the relationships of verbal memory impairments with cognitive underpinnings on the one hand, and clinical symptomatology on the other. The results have been reported in previous papers. In this paper we show how all these data could be integrated into a consistent pattern of associations. METHOD: Fifty schizophrenic patients underwent a cognitive battery including a verbal memory task with free recall and recognition, a source memory task, and tests of processing speed and selective attention. Ratings for positive, negative and depressive symptoms were available for 40 of the patients. RESULTS: A factorial analysis revealed a distinction between measures of memory efficiency and measures of memory errors. The system of memory efficiency was associated with processing speed and selective attention at the cognitive level, and with depression at the symptom level. The system of memory errors was assumed to be underlain by source-monitoring deficits. These memory errors were increased by positive symptoms and decreased by certain negative symptoms. CONCLUSIONS: All the measures drawn from various memory tasks could be integrated into a model describing their associations with cognitive underpinnings and clinical symptomatology. This model provides a heuristic for the cognitive and pharmacological treatments of verbal memory impairments in schizophrenia, as well as for the understanding of positive symptoms.

Adult↗

PubMed2001

Limitations of the Paced Auditory Serial Addition Test as a measure of working memory in patients with multiple sclerosis.

The Paced Auditory Serial Addition Test (PASAT) is a commonly used procedure that combines elements of both a working memory task and a test of information processing speed. Patients with multiple sclerosis (MS) have consistently been found to be impaired on this test and it has been recommended as a core outcome measure in clinical trials. The standard score for this task is the number of correct responses at each stimulus presentation rate but a concern has been raised that subjects may ignore some test items in order to chunk the information into manageable portions and avoid performing several cognitive tasks simultaneously. To account for this strategy, one can examine the proportion of correct responses that are consecutive (termed dyads), since such responses require that the task be performed according to the instructions. We compared a group of 35 mildly to moderately disabled MS patients and matched healthy controls on the PASAT. The MS patients made significantly fewer correct responses at the 2 slowest presentation rates (2.4, 2.0 s/digit) while their scores at faster rates (1.6, 1.2 s/digit) did not discriminate them from controls as well. Nevertheless, the MS patients' percentage of dyads was significantly lower than that of the control sample across all stimulus presentation rates. While our study supports the use of the PASAT as a test that distinguishes MS patients from healthy individuals, our results also illustrate problems that lie in the interpretation of this difference in performance. It appears that a chunking strategy may be common in the PASAT, particularly as task demands increase, and that this may mask actual performance differences. If so, the total correct response score alone is limited as a measure of working memory and information processing speed. More detailed analyses of PASAT performance, coupled with other measures of information processing, may help clarify the underlying cognitive deficits of MS patients.

Adult↗

PubMed2004

Factors affecting increasing radiation dose for mammography in North Carolina from 1997 through 2001: an analysis of Food and Drug Administration annual surveys.

RATIONALE AND OBJECTIVES: To determine which factors affected the increase in average glandular dose recorded at the annual US Food and Drug Administration Mammography Quality Standards Act inspections of mammography equipment in North Carolina from 1997 to 2001. MATERIALS AND METHODS: Average glandular dose, HVL, kVp, ambient light, luminance, equipment age, processing speed, and system speed for every mammography unit at all facilities in the state were collected by state inspectors. A mixed-effect model was used to assess the average changes of glandular dose over time and to identify the factors associated with these changes. RESULTS: There was a statistically significant increase in the average glandular dose in North Carolina in 1999, 2000, and 2001 when compared with the baseline year of 1997. Factors that were statistically significantly linked to this effect were changes in kVp, processing speed, and system speed. CONCLUSION: Average glandular dose for mammography has recently increased in North Carolina. This change is likely caused by changes in screen-film products and processing techniques.

Annual Reports as Topic↗

PubMed1991

Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test.

Forty-six Attention Deficit Disorder (ADD) adolescents took a Continuous Performance Test (CPT) under placebo and methylphenidate (35.33 mg/day). The task required pressing one button for targets (p = .133), and another button for nontargets. Subjects displayed a strong bias to make the more frequent negative response before completely evaluating stimuli. Consistent with this assumption, subjects responded faster (by an average of 87 ms) to nontargets than to targets. Methylphenidate increased accuracy and speeded reaction times (RTs) to targets. The drug also increased the amplitude of the P3b component of the event-related potential for nontargets and shortened the latency of P3b for both targets and nontargets. These results suggest increased capacity allocation to and faster evaluation of task stimuli. Finally, the stimulant lengthened relative motor processing time (RT-P3b latency) for nontargets, a finding implying that response processing was accomplished with the benefit of earlier completion of evaluation processes for these stimuli.

Adolescent↗

PubMed1997

General lexical slowing and the semantic priming effect: the roles of age and ability.

Older adults performed three lexical information-processing tasks approximately 1.3 times slower than young adults. Consistent with general lexical slowing, slopes of regressions based on individual subjects' RTs on two of the tasks (single lexical decision and category judgment) did not differ from slopes based on the third (double lexical decision) task. Moreover, slopes based on the single lexical decision and category judgment tasks accurately predicted the size of semantic priming effects on the third (double lexical decision) task. This was true for the older group as a whole, and also for subgroups of fast, medium and slow older adults, as well as for young adult subgroups. The size of the semantic priming effects for the fast old and slow young subgroups (who differed in age but not in processing speed) were approximately equal, consistent with the idea that the effect of age on priming is entirely attributable to slowing. Across all tasks, each old subgroup (fast, medium, or slow) showed the same degree of slowing relative to the corresponding young subgroup, so that the differences in RTs observed between subgroups in the young sample were magnified in the old sample. Taken together, the present findings suggest that ability-related differences in lexical processing speed may be functionally equivalent to age-related differences and that both factors interact to determine performance on speeded lexical tasks.

Adult↗

PubMed2004

Components of executive function in typically developing and head-injured children.

To identify the key components of executive functions (EFs) in children following traumatic brain injury (TBI), data from a series of EF tests administered to 286 pediatric TBI patients at least 3 years postinjury were subjected to an exploratory factor analysis. A 5-factor model included discourse, EFs (e.g., problem solving, planning), processing speed (e.g., coding), declarative memory, and motor speed. Confirmatory factor analysis based on data obtained from 265 pediatric TBI patients at 3 months postinjury disclosed that the 5-factor model provided a good fit to the data. A second exploratory analysis of the 3-month postinjury data disclosed a 4-factor model in which processing speed and motor speed measures loaded on a common factor. Severity of TBI and age at test had significant effects on all factors in both the 5- and 4-factor models. Adaptive functioning, as measured by the Vineland Adaptive Behavioral Scale-Revised, was moderately related to factor scores at 3 years or longer postinjury, but weakly related to factor scores obtained at 3 months postinjury. The factor scores could be used in clinical trials to facilitate data reduction and appear to have validity as indicators of TBI outcome.

Activities of Daily Living↗

PubMed2002

Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender.

BACKGROUND: Executive function, particularly behavioral inhibition, has been implicated as a core deficit specific to Attention-Deficit/Hyperactivity Disorder (ADHD) whereas rapid naming has been implicated as a core deficit specific to reading disabilities (RD). Females may be less impaired in executive function although adolescent females with ADHD have yet to be studied. METHOD: Neuropsychological profiles of four adolescent groups aged 13-16 with equal female representation were investigated: 35 ADHD, 12 RD, 24 ADHD+RD, and 37 normal controls. A semi-structured interview (K-SADS-PL), the Conners Rating Scales and the Ontario Child Health Study Scales were used to diagnose ADHD. RD was defined as a standard score below 90 on at least one of the following: Reading or Spelling of the WRAT3 or Word Attack or Word Identification of the WRMT-R. The WISC-III, Rapid Automatized Naming, Stroop and Stop tasks were used as measures of cognitive and executive function. RESULTS: The two ADHD groups (ADHD, ADHD+RD) showed deficits in processing speed, naming of objects, poor behavioral inhibition and greater variability in reaction times whereas the two RD groups (RD, RD+ADHD) showed verbal working memory deficits and slower verbal retrieval speed. Only the comorbid group was slower with naming of numbers and colors and had slower reaction times. Regression analyses indicated that incongruent color naming (Stroop) and variability in go reaction time were the best predictors of hyperactive/impulsive ADHD symptoms whereas variability in go reaction time and processing speed were the best predictors of inattentive ADHD symptoms. Speed of letter naming and verbal working memory accounted for the most variability in composite achievement scores. No gender differences were found on any of the cognitive tests. CONCLUSIONS: This study challenges the importance of behavioral inhibition deficits in ADHD and that naming deficits are specific to RD. Further investigation into cognitive deficits in these groups is required.

Adolescent↗

PubMed2004

Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study.

This pilot study examines whether hormone therapy for breast cancer affects cognition. Patients participating in a randomised trial of anastrozole, tamoxifen alone or combined (ATAC) (n=94) and a group of women without breast cancer (n=35) completed a battery of neuropsychological measures. Compared with the control group, the patients were impaired on a processing speed task (p=0.032) and on a measure of immediate verbal memory (p=0.026) after controlling for the use of hormone replacement therapy in both groups. Patient group performance was not significantly related to length of treatment or measures of psychological morbidity. The results showed specific impairments in processing speed and verbal memory in women receiving hormonal therapy for the treatment of breast cancer. Verbal memory may be especially sensitive to changes in oestrogen levels, a finding commonly reported in studies of hormone replacement therapy in healthy women. In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly.

Affect↗

PubMed2006

The WAIS-III and major depression: absence of VIQ/PIQ differences.

Poor Performance IQ (PIQ) relative to Verbal IQ (VIQ) is a standard finding in depressed patients administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R). This study examined performance of depressed subjects on the instrument's latest revision, the WAIS-III, which provides a more detailed subdomain profile of intellectual functioning. WAIS-III IQ, index and subscale scores were compared between 121 unmedicated subjects in major depressive episode and 41 healthy volunteers, using demographically adjusted T-score conversions. Depressed subjects had significantly lower PIQ scores, but neither the absolute VIQ/PIQ difference nor prevalence of VIQ/PIQ discrepancies >1 SD differed between groups. Index score differences were exclusively in Processing Speed, and subtest differences only on timed tasks. WAIS-III scores did not differ between subjects with major depressive and bipolar disorders, nor between subjects with and without melancholia or history of suicidal behavior. Results suggest general intellectual performance in depression is best characterized by deficits in processing speed, rather than global nonverbal abilities, and that this deficit is consistent across depression subtypes.

Adult↗

PubMed1999

Asymmetric dependencies in perceiving identity and emotion: experiments with morphed faces.

We investigated whether an asymmetric relationship between the perception of identity and emotional expressions in faces (Schweinberger & Soukup, 1998) may be related to differences in the relative processing speed of identity and expression information. Stimulus faces were morphed across identity within a given emotional expression, or were morphed across emotion within a given identity. In Experiment 1, consistent classifications of these images were demonstrated across a wide range of morphing, with only a relatively narrow category boundary. At the same time, classification reaction times (RTs) reflected the increased perceptual difficulty of the morphed images. In Experiment 2, we investigated the effects of variations in the irrelevant dimension on judgments of faces with respect to a relevant dimension, using a Garner-type speeded classification task. RTs for expression classifications were strongly influenced by irrelevant identity information. In contrast, RTs for identity classifications were unaffected by irrelevant expression information, and this held even for stimuli in which identity was more difficult and slower to discriminate than expression. This suggests that differences in processing speed cannot account for the asymmetric relationship between identity and emotion perception. Theoretical accounts proposing independence of identity and emotion perception are discussed in the light of these findings.

Adult↗

PubMed2006

Age-related change in executive function: developmental trends and a latent variable analysis.

This study examined the developmental trajectories of three frequently postulated executive function (EF) components, Working Memory, Shifting, and Inhibition of responses, and their relation to performance on standard, but complex, neuropsychological EF tasks, the Wisconsin Card Sorting Task (WCST), and the Tower of London (ToL). Participants in four age groups (7-, 11-, 15-, and 21-year olds) carried out nine basic experimental tasks (three tasks for each EF), the WCST, and the ToL. Analyses were done in two steps: (1) analyses of (co)variance to examine developmental trends in individual EF tasks while correcting for basic processing speed, (2) confirmatory factor analysis to extract latent variables from the nine basic EF tasks, and to explain variance in the performance on WCST and ToL, using these latent variables. Analyses of (co)variance revealed a continuation of EF development into adolescence. Confirmatory factor analysis yielded two common factors: Working Memory and Shifting. However, the variables assumed to tap Inhibition proved unrelated. At a latent level, again correcting for basic processing speed, the development of Shifting was seen to continue into adolescence, while Working Memory continued to develop into young-adulthood. Regression analyses revealed that Working Memory contributed most strongly to WCST performance in all age groups. These results suggest that EF component processes develop at different rates, and that it is important to recognize both the unity and diversity of EF component processes in studying the development of EF.

Adolescent↗

PubMedDate not supplied

Efficient generation, storage, and manipulation of fully flexible pharmacophore multiplets and their use in 3-D similarity searching.

Pharmacophore triplets and quartets have been used by many groups in recent years, primarily as a tool for molecular diversity analysis. In most cases, slow processing speeds and the very large size of the bitsets generated have forced researchers to compromise in terms of how such multiplets were stored, manipulated, and compared, e.g., by using simple unions to represent multiplets for sets of molecules. Here we report using bitmaps in place of bitsets to reduce storage demands and to improve processing speed. Here, a bitset is taken to mean a fully enumerated string of zeros and ones, from which a compressed bitmap is obtained by replacing uniform blocks ("runs") of digits in the bitset with a pair of values identifying the content and length of the block (run-length encoding compression). High-resolution multiplets involving four features are enabled by using 64 bit executables to create and manipulate bitmaps, which "connect" to the 32 bit executables used for database access and feature identification via an extensible mark-up language (XML) data stream. The encoding system used supports simple pairs, triplets, and quartets; multiplets in which a privileged substructure is used as an anchor point; and augmented multiplets in which an additional vertex is added to represent a contingent feature such as a hydrogen bond extension point linked to a complementary feature (e.g., a donor or an acceptor atom) in a base pair or triplet. It can readily be extended to larger, more complex multiplets as well. Database searching is one particular potential application for this technology. Consensus bitmaps built up from active ligands identified in preliminary screening can be used to generate hypothesis bitmaps, a process which includes allowance for differential weighting to allow greater emphasis to be placed on bits arising from multiplets expected to be particularly discriminating. Such hypothesis bitmaps are shown to be useful queries for database searching, successfully retrieving active compounds across a range of structural classes from a corporate database. The current implementation allows multiconformer bitmaps to be obtained from pregenerated conformations or by random perturbation on-the-fly. The latter application involves random sampling of the full range of conformations not precluded by steric clashes, which limits the usefulness of classical fingerprint similarity measures. A new measure of similarity, The Stochastic Cosine, is introduced here to address this need. This new similarity measure uses the average number of bits common to independently drawn conformer sets to normalize the cosine coefficient. Its use frees the user from having to ensure strict comparability of starting conformations and having to use fixed torsional increments, thereby allowing fully flexible characterization of pharmacophoric patterns.

Adrenergic beta-Antagonists↗