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PubMed2002

Factor structure of the Wechsler Adult Intelligence Scale-III in schizophrenia.

This report examines and compares the factor structure of the new edition of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of chronic schizophrenia and schizoaffective disorder outpatients (n = 120) and an age-matched sample of individuals drawn from the WAIS-III standardization sample (n = 200). Exploratory and confirmatory factor analyses similar to those reported by the developers of the scale suggested that a model of WAIS-III performance with correlated factors for verbal comprehension, perceptual organization, working memory, and processing speed fit the data from the schizophrenia sample as well as it fit the nonclinical comparison sample and fit the data from both samples better than alternative models.

Adult↗

PubMed2006

WISC-IV and WISC-III profiles in children with ADHD.

Wechsler Intelligence Scale for Children, 3rd and 4th editions (WISC-III n = 586 and WISC-IV n = 118), profiles were compared for children with ADHD and normal intelligence. Mean Verbal Comprehension Index (VCI) and Perceptual Organization/Perceptual Reasoning Index (POI/PRI) scores were significantly higher than Freedom From Distractibility/Working Memory Index (FDI/WMI) and Processing Speed Index (PSI), and Symbol Search was higher than Coding. FDI/WMI and PSI scores were similar on both tests, but VCI and POI/PRI were higher on the WISC-IV than on the WISC-III. Therefore, index discrepancies were greater for the WISC-IV, suggesting that the WISC-IV might be better than the WISC-III in delineating the strengths and weaknesses of children with ADHD. All children in the WISC-IV sample scored lowest on WMI or PSI, whereas only 88% of the WISC-III children scored lowest on FDI or PSI. Thus, the WISC-IV may be more helpful in diagnosing ADHD than the WISC-III.

Adolescent↗

PubMed1999

Miniaturization of a Mammalian Cell-Based Assay: Luciferase Reporter Gene Readout in a 3 Microliter 1536-Well Plate.

The combined efforts of the fields of combinatorial chemistry and genomics have significantly increased the number of compounds and therapeutic targets available for screening. The number of compounds will reach into the million range in the near future and provide vast chemical diversity for drug discovery. However, this reservoir of chemical diversity creates downstream hurdles for any screening effort. Properly examining this number of compounds increases investments dramatically, both in the number of dollars spent and amount of limited reagents depleted. Traditional HTS techniques, such as the use of 96-well microtiter plates, have paved the way for faster processing speeds, but are being rapidly overwhelmed by screening demands. Miniaturization of such assays will allow for greater throughput, while concurrently reducing cost. To date, miniaturization efforts have been most successfully applied to bacterial and soluble protein based assays. Questions about the ability to deliver microquantities of mammalian cells without disruption of the cell membrane and/or activation of stress responses have been raised. An assay has been developed in which a human T-cell screen has been adapted to a 1536-well plate format. Through the use of a luciferase reporter gene system, it is shown that a mammalian cell-based assay may be successfully performed in 3 µl and potent inhibitors of the target of interest identified.

Journal Article↗

PubMed2006

Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide poisoning.

Carbon monoxide is a colorless, odorless gas produced as a byproduct of combustion. Carbon monoxide is the leading cause of poisoning injury and death worldwide. Morbidity following CO poisoning includes neurologic sequelae, neuropathologic abnormalities on brain imaging, neurobehavioral changes, and cognitive impairments. It is estimated that as high as 50% of individuals with carbon monoxide poisoning will develop neurologic, neurobehavioral, or cognitive sequelae. Carbon monoxide related cognitive impairments included impaired memory, attention, executive function, motor, visual spatial, and slow mental processing speed. Given the high rate of brain related morbidity and the fact that the majority of carbon monoxide is avoidable, awareness and prevention of carbon monoxide poisoning is warranted.

Brain Injuries↗

PubMed2004

Event-related potentials in young and elderly adults during a visual spatial working memory task.

The P300 event-related brain potential (ERP) was examined in 14 young (20-29 years of age) and 16 elderly (60-82 years of age) subjects during the performance of a visuospatial memory task requiring recognition of locations. Elderly and young adults exhibited similar recognition accuracy, but recognition reaction times were significantly slower in the elderly. Midline P300 amplitudes recorded in response to visuospatial probe stimuli were significantly attenuated in the elderly, and, depending on the nature of the probe, P300 latency-derived indices indicated that both cognitive and motoric slowness characterized visuospatial recognition in the aged. The results, discussed in relation to neural mechanisms supporting working memory function, suggest that alterations in attention and processing speed may play a role in visual-spatial working memory deficits associated with normal and pathological aging.

Adult↗

PubMed1997

Enhancement of attention processing by Kantroll in healthy humans: a pilot study.

This is the first report in humans of the effects of daily ingestion of a specific amino acid mixture, Kantroll, on cognitive event-related potentials (ERPs) associated with performance. Cognitive ERPs were generated by two computerized visual attention tasks, the Spatial Orientation Task (SOT) and Contingent Continuous Performance Task (CCPT), in normal young adult volunteers, where each subject acted as his own control for testing before and after 28-30 days of amino acid ingestion. A statistically significant amplitude enhancement of the P300 component of the ERPs was seen after Kantroll for both tasks, as well as improvement with respect to cognitive processing speeds. The enhancement of neurophysiologic function observed in this study on normal controls is consistent with the facilitation of recovery of individuals with RDS (i.e., substance use disorder, ADHD, carbohydrate bingeing) following the ingestion of the amino acid supplement, Kantroll, and warrants additional placebo-controlled, double-blind, studies to confirm and extend these results.

Adult↗

PubMed2006

Neuropsychiatric manifestations of multiple sclerosis.

Multiple sclerosis is one of the most frequently observed neurological causes of progressive disability in early to middle adulthood. The disease is variable in its presentation and course, affects roughly 100 to 300 per 100,000 persons within the US alone and is slightly more common among females than males. Multiple sclerosis places substantial burdens on patients, families and caregivers. Its presentation includes disturbances in cognitive abilities and psychiatric functioning, as well as motor difficulties. This article reviews the current literature on the neuropsychiatric manifestations of multiple sclerosis. Cognitive domains discussed include general cognitive functioning, learning and memory ability, attention, processing speed, executive functioning, visual perceptual ability and language functioning. Attention is also given to alterations in neuropsychiatric functioning associated with disease progression and across various disease subtypes. In addition, reports are also reviewed regarding various psychiatric disturbances, affective changes, quality of life issues and fatigue and pain in individuals with multiple sclerosis. Finally, factors pertaining to pediatric populations in multiple sclerosis are addressed.

Attention↗

PubMed2004

No evidence of association between Catechol-O-Methyltransferase (COMT) Val158Met genotype and performance on neuropsychological tasks in children with ADHD: a case-control study.

BACKGROUND: Several studies have suggested an association between the functional Val158Met polymorphism in the Catechol-O-Methyltransferase (COMT) gene and neurocognitive performance. Two studies showed that subjects with the low activity Met allele performed better on the Wisconsin Card Sorting Test (WCST) and another study found an effect on processing speed and attention. METHODS: We set out to examine the association between the Val158Met polymorphism and performance on neurocognitive tasks including those tapping working memory, attention and speed, impulsiveness and response inhibition in a sample of 124 children with ADHD. Task performance for each genotypic group was compared using analysis of variance. RESULTS: There was no evidence of association with performance on any of the neurocognitive tasks. CONCLUSIONS: We conclude that Val158Met COMT genotype is not associated with neurocognitive performance in our sample.

Adolescent↗

PubMed2006

Working memory deficits in adults with ADHD: is there evidence for subtype differences?

BACKGROUND: Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. METHODS: This study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT). RESULTS: The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. CONCLUSION: In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.

Journal Article↗

PubMed2002

Determinants of health-related quality of life in multiple sderosis: the role of illness intrusiveness.

The relationship between the cognitive and physical aspects of multiple sclerosis (MS) and health-related quality of life (HRQL) was examined with particular focus on illness intrusiveness as a mediator of this relationship. Disease severity, cognitive functioning HRQL, depression, and illness intrusiveness were assessed in 90 patients with MS. Disease severity (Expanded Disability Status Scale [EDSS]) predicted physical aspects of HRQL (SF-36 Physical Component Summary [PCS], fatigue, and bladder control). Information-processing speed (Paced Auditory Serial Addition Test [PASAT]) predicted mental and emotional aspects of HRQL (SF-36 Mental Component Summary [MCS]). However, both the EDSS and the PASAT predicted depression. Illness intrusiveness was significantly correlated with all indicators of HRQL Illness intrusiveness also mediated the manner in which disease severity predicted: physical health, fatigue, and depression. Results underscore the need to assess MS and its impact more broadly rather than relying on traditional mobility-centered assessments. While in most cases physical indices of disease predict physical quality of life and cognitive assessments predict mental and emotional quality of life, the individuals perception of MS is also a major factor contributing to quality of life. MS dearly affects multiple aspects of life and activity, as illustrated by the broad and powerful network of relationships between illness intrusiveness and all aspects of HRQL Perceptions of illness intrusiveness appear to be a central and essential measure of the impact of MS on HRQL.

Activities of Daily Living↗

PubMed2003

Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire.

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Questionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. Analyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. Cronbach's alpha coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.

Adult↗

PubMed2005

Subjective cognitive complaints relate to mild impairment of cognition in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), but cannot be reliably predicted by physical impairment. The negative impact of cognitive impairment makes early detection important, but subjective cognitive complaints may be attributed to depression. We examined the relationship between subjectively reported and objectively measured cognitive impairment in MS, adjusting for mood. A neuropsychological battery, the Multiple Sclerosis Functional Composite (MSFC), the Mental Health Inventory (MHI), the Modified Fatigue Impact Scale (MFIS), the Perceived Deficits Questionnaire (PDQ) were administered to 136 patients. Demographically-adjusted cognitive scores were calculated. Subjective impairment was defined as PDQ score >2 standard deviations above that for healthy persons. We modeled the relationship of cognitive scores (independent variables) to being subjectively impaired (dependent variable) using logistic regression. Immediate Memory (IM) and Processing Speed Index (PSI) scores were non-linearly related to subjective impairment Patients were less likely to report subjective impairment if their PSI was normal (OR =0.11; 0.02-0.73) or markedly impaired (OR =0.17; 0.03-0.91), compared to mildly reduced PSI. In young patients decreases in IM were associated with increased subjective impairment (OR = 1.25; 1.07-1.47). Subjectively reported impairment reflects subtle declines in PSI and IM independent of mood, fatigue, and physical impairment Cognitive complaints should not be discounted due to depression.

Adult↗

PubMed2005

Pattern of neuropsychological impairment in the early phase of relapsing-remitting multiple sclerosis.

To investigate the neuropsychological profile in the first few years post-onset of relapsing-remitting multiple sclerosis (MS) we carried out a comprehensive neuropsychological evaluation of 33 patients characterized by very short evolution of this disease, minimal levels of neurological disability and preserved general cognition. Thirty-three individually pair-matched controls were also evaluated. Patients performed as well as controls on many of the cognitive exploration measures. Nevertheless, the group of patients evinced a general slowness that affected motor execution and cognitive processing. Memory functions were characterized by preservation of working memory, retrieval or storage of information and a deficit at the acquisition phase in (verbal and visual) supraspan tasks. In addition, significant correlations were observed between some measures of information processing speed and memory. These results highlight the importance of studying cognitive deficits not only in the different subtypes of MS but also in different phases of the disease.

Adult↗

PubMed1976

Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.

Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.

Antipsychotic Agents↗

PubMed1992

The effect of neuroleptics on cognitive and psychomotor function. A preliminary study in healthy volunteers.

The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and caffeine (400 mg) on subjective and objective measures of cognitive and psychomotor function were compared with placebo in 20 healthy volunteers. While both diazepam and benzhexol were associated with highly significant impairments in subjective altertness, critical flicker fusion threshold and choice reaction time (CRT), haloperidol could not be distinguished from placebo in most tests but was actually associated with an apparent improvement in CRT (in males) and simple visual reaction time. The perceptual maze test detected impairment by benzhexol on processing speed but was not sensitive to any other drug effects. Multiple-dose studies are required to establish if there is a true activating effect of haloperidol using a test of sustained attention. No effect of Eysenck personality subtype or life events on baseline or drug response data was detected.

Adult↗

PubMed1992

The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease.

To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

PubMed2005

ADHD deficit as measured in adolescent boys with a continuous performance task is related to antenatal maternal anxiety.

Antenatal maternal anxiety has been shown to be related to infant temperament, childhood disorders, and impulsivity in adolescence. This study prospectively investigated whether antenatal maternal anxiety is associated with performance on a continuous performance task. Sixty-four adolescents (mean age, 15 y; 34 boys, 30 girls) were examined with a computerized continuous performance task (CPT) measuring sustained attention. Results showed that the CPT performance of boys of mothers with high levels of state anxiety during the 12th to 22nd postmenstrual week of pregnancy declined as the task progressed: their processing speed became slower and the variability in their reaction times increased. The study controlled for the possible confounding influences of postnatal maternal anxiety, the parents' educational level, and intelligence. Establishing a link between antenatal maternal anxiety and an objective measure of sustained attention/self-regulation, our results extend the growing evidence for an association between antenatal maternal anxiety and the neurobehavioral development of the offspring up into adolescence.

Adolescent↗

PubMed1996

Neuropsychological assessment in a case of pseudoneurologic symptamology.

A 35-year-old woman undergoing an evaluation for possible multiple sclerosis had deficits in motor coordination, information processing speed, memory, verbal fluency and executive functions on neuropsychological testing Although presenting symptoms and cognitive impairments suggested multiple sclerosis, clinical history, personality features and neurologic workup were more consistent with a somatoform disorder This case illustrates the importance of interpreting neuropsychological deficits within a broad clinical context.

Journal Article↗