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PubMed2006

Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy.

PURPOSE: All major antiepileptic drugs (AEDs) have been reported to be associated with cognitive side effects. Uncertainty exists regarding the degree of cognitive effects, primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of discontinuation of AEDs in patients receiving monotherapy on measures of attention, reaction time, and speed of information processing. METHODS: The 150 subjects who had been seizure free>2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after discontinuation. RESULTS: The major finding in this study is that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the two groups on these tasks was between 24 to 43 ms. Simple tasks of attention and reaction time revealed no significant differences between the discontinuation group and the nondiscontinuation group. Most of the subjects in the study were medicated with carbamazepine (CBZ) and valproate (VPA). The outcome of discontinuation of CBZ was similar to the outcome for the total study population, whereas withdrawal of VPA revealed only a nonsignificant tendency in the same direction. CONCLUSIONS: The results suggest that seizure-free epilepsy patients receiving monotherapy can obtain improvement in cognitive function if they discontinue AED treatment.

Adolescent↗

PubMed2004

Preclinical memory profile in Alzheimer patients with and without allele APOE-epsilon4.

To investigate the association between APOE-epsilon4 allele and memory phenotype in the preclinical stage of Alzheimer's disease (AD). We compared an extensive preclinical memory profile at the baseline evaluation of 2 AD genotype groups: APOE-epsilon4 allele carriers and patients with APOE-epsilon3 homozygosity. Baseline memory performance was carried out at least 2 years (interval of 27.7 +/- 4 months) before AD diagnosis was established, and analysis included different modalities of working memory (visuoperceptive, visuospatial, digit span and processing speed), of declarative memory (recent, verbal learning, prospective and semantic) and of nondeclarative memory (procedural, incidental and priming). We found no significant differences: memory performance was similar in both genotype groups. The presence of the APOE-epsilon4 allele does not seem to be sufficient to cause a distinctive preclinical memory phenotype in AD patients.

Aged↗

PubMed2003

Gender influence on cognitive function after cardiac operation.

BACKGROUND: Women are at higher risk than men for stroke after cardiac operation. The purpose of this study was to evaluate for gender influences on the more common postoperative neurologic complication, cognitive dysfunction. METHODS: A standard battery of neuropsychological tests was administered to 117 patients (79 men and 38 women) the day before and again 4 to 6 weeks after cardiac operation. The battery assessed a broad array of cognitive domains, including attention, memory, executive function, and psychomotor processing speed. Analysis was performed only on patients with data from both testing sessions. Data were analyzed to assess for a dichotomous definition of postoperative cognitive impairment and to evaluate for factors influencing test results for specific cognitive domains. RESULTS: The frequency of one standard deviation decline on two or more cognitive tests compared with preoperative results (women, 10.7 % versus men, 9.9 %; p = 0.527), no decline, or one standard deviation improvement on each test postoperatively was no different between genders. After adjusting for age, gender, preexisting medical conditions, level of attained education, preoperative cognitive tests results, type of operation, and duration of cardiopulmonary bypass, female gender was independently associated with poorer performance postoperatively on visuospatial tasks. Other variables significantly related to postoperative cognitive function varied among the specific cognitive domains. CONCLUSIONS: These data suggest that, although the frequency of cognitive dysfunction after cardiac operation is similar for women and men, women appear more likely to suffer injury to brain areas subserving visuospatial processing. Risk factors for postoperative cognitive impairment vary depending on cognitive domain, suggesting multiple etiologies for this form of perioperative neurologic injury.

Cardiac Surgical Procedures↗

PubMedDate not supplied

MR lesion load and cognitive function in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disease most often associated with progressive physical impairment; however, its effects are noted to extend beyond physical disability. Our purpose was to determine the relationship between T2 lesion volume and neurocognitive and physical disability in relapsing-remitting multiple sclerosis. METHODS: We studied a cohort of 19 patients with relapsing-remitting MS. Of this group, there were 15 women and four men from varying socioeconomic backgrounds. This volunteer sample was selected from a larger group of 53 patients with MS in our longitudinal MS study because they had been untreated with any beta-interferon medications, had been followed for at least 12 months, and had a clinical status of relapsing-remitting MS. RESULTS: Of 12 neurocognitive parameters tested, two correlated significantly with lesion loads. The correlation of the Symbol-Digit Modalities test, which analyzes information-processing speed, was significant (P = .0204). The correlation of the fifth trial of the Rey Auditory Verbal Learning test, which tests verbal long-term memory, was also significant (P = .0348). None of the other 10 neurocognitive examinations, however, showed a significant correlation with total lesion volume (Paced Auditory Serial Addition test-1.6, P = .7381; Paced Auditory Serial Addition test-2.0, P = .4180; Controlled Oral Word Association test, P = .8906; Category Fluency test, P = .4423; Bells test, P = .9097; Rey Auditory Verbal Learning test-delay, P = .9843, Rey Auditory Verbal Learning test-recognition, P = .7467; Word Span test, P = .4939; Road Map test, P = 0.4939). The lesion load also did not correlate with the physical disability scales as rated according to the Expanded Disability Status Scale (P = .68) or Ambulation Index (P = .95). CONCLUSION: Our results indicate that T2 lesion volume does not seem to be a robust surrogate marker of neuropsychological impairment in patients with MS. We think that global measurements of parameters that are more specific to the disease process may offer more precise correlation with cognitive dysfunction and other disability parameters.

Adult↗

PubMed1987

Neurobehavioral outcome following minor head injury: a three-center study.

The majority of hospital admissions for head trauma are due to minor injuries; that is, no or only transient loss of consciousness without major complications and not requiring intracranial surgery. Despite the low mortality rate following minor head injury, there is controversy surrounding the extent of morbidity and the long-term sequelae. The authors postulated that consecutively admitted patients who fulfilled research diagnostic criteria for minor head injury and who were carefully screened for antecedent neuropsychiatric disorder and prior head injury would exhibit subacute cognitive and memory deficits that would resolve over a period of 1 to 3 months postinjury. To evaluate this hypothesis, the neurobehavioral functioning of 57 patients was compared within 1 week after minor head injury (baseline) and at 1 month postinjury with that of 56 selected control subjects at three medical centers. Quantified tests of memory, attention, and information-processing speed revealed that neurobehavioral impairment demonstrated at baseline by all means of measurement generally resolved during the first 3 months after minor head injury. Although nearly all patients initially reported cognitive problems, somatic complaints, and emotional malaise, these postconcussion symptoms had substantially resolved by the 3-month follow-up examination. The data suggest that a single uncomplicated minor head injury produces no permanent disabling neurobehavioral impairment in the great majority of patients who are free of preexisting neuropsychiatric disorder and substance abuse.

Adolescent↗

PubMed2005

An integrated approach to fast and informative morphological vouchering of nematodes for applications in molecular barcoding.

Molecular surveys of meiofaunal diversity face some interesting methodological challenges when it comes to interstitial nematodes from soils and sediments. Morphology-based surveys are greatly limited in processing speed, while barcoding approaches for nematodes are hampered by difficulties of matching sequence data with traditional taxonomy. Intermediate technology is needed to bridge the gap between both approaches. An example of such technology is video capture and editing microscopy, which consists of the recording of taxonomically informative multifocal series of microscopy images as digital video clips. The integration of multifocal imaging with sequence analysis of the D2D3 region of large subunit (LSU) rDNA is illustrated here in the context of a combined morphological and barcode sequencing survey of marine nematodes from Baja California and California. The resulting video clips and sequence data are made available online in the database NemATOL (http://nematol.unh.edu/). Analyses of 37 barcoded nematodes suggest that these represent at least 32 species, none of which matches available D2D3 sequences in public databases. The recorded multifocal vouchers allowed us to identify most specimens to genus, and will be used to match specimens with subsequent species identifications and descriptions of preserved specimens. Like molecular barcodes, multifocal voucher archives are part of a wider effort at structuring and changing the process of biodiversity discovery. We argue that data-rich surveys and phylogenetic tools for analysis of barcode sequences are an essential component of the exploration of phyla with a high fraction of undiscovered species. Our methods are also directly applicable to other meiofauna such as for example gastrotrichs and tardigrades.

Animals↗

PubMed2003

Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life.

Low-grade gliomas frequently are associated with epilepsy. The purpose of this study is to determine the impact of epilepsy and antiepileptic drug (AED) treatment on cognitive functioning and health-related quality of life (HRQOL) in these patients. One hundred fifty-six patients without clinical or radiological signs of tumor recurrence for at least 1 year after histological diagnosis and with an epilepsy burden (based on seizure frequency and AED use) ranging from none to severe were compared with healthy controls. The association between epilepsy burden and cognition/HRQOL was also investigated. Eighty-six percent of the patients had epilepsy and 50% of those using AEDs actually were seizure-free. Compared with healthy controls, glioma patients had significant reductions in information processing speed, psychomotor function, attentional functioning, verbal and working memory, executive functioning, and HRQOL. The increase in epilepsy burden that was associated with significant reductions in all cognitive domains except for attentional and memory functioning could primarily be attributed to the use of AEDs, whereas the decline in HRQOL could be ascribed to the lack of complete seizure control. In conclusion, low-grade glioma patients suffer from a number of neuropsychological and psychological problems that are aggravated by the severity of epilepsy and by the intensity of the treatment.

Adult↗

PubMed2005

Within session practice effects on the PASAT in clients with multiple sclerosis.

Impaired information processing speed (IPS) is common in multiple sclerosis (MS). As a measure of IPS the Paced Auditory Serial Addition Test (PASAT), the measure recommended for serial assessments by the National MS Society Task Force, is influenced by practice effects. Within session practice effects for the PASAT were examined in a sample of 30 individuals with MS. Significant practice effects on all PASAT trials were identified, with the exception of the slowest trial. Those with relapsing-remitting MS showed greater improvement on repeated assessment than those with chronic-progressive MS, on all except the slowest PASAT trial. It was concluded that, due to the extensive practice effects found at faster presentation, serial use of the PASAT in MS samples should either rely on use of slower presentations, or include some correction to account for practice effects.

Adult↗

PubMed2006

White matter damage on diffusion tensor imaging correlates with age-related cognitive decline.

BACKGROUND: Damage to white matter tracts, resulting in "cerebral disconnection," may underlie age-related cognitive decline. METHODS: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. RESULTS: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance in all three cognitive domains. After controlling for age, DTI parameters correlated with working memory but not with the other two cognitive domains. MRS studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI parameters (r = 0.253, p < 0.05). CONCLUSION: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

Aged↗

PubMed2006

Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children.

AIM: The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. METHODS: Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. RESULTS: 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. CONCLUSION: After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

Adolescent↗

PubMed1990

Auditive and cognitive factors in speech perception by elderly listeners.

A key issue in research on speech perception in the elderly is whether the difficulties in understanding speech are caused by auditive and/or cognitive factors. Resolving this issue is not only scientific interest but has many practical, i.e. diagnostic and rehabilitative, implications as well. We developed a test battery comprising auditive (sensitivity, frequency selectivity and temporal resolution), cognitive (memory performance, processing speed and intellectual abilities), and speech perception tests (at the phoneme, spondee and sentence level). This test battery was administered to 72 elderly subjects (aged 60 to 93 years). The results show that the deterioration of speech perception in the elderly consists of two statistically independent components (a) a large component mainly representing the progressive high-frequency hearing loss with age which accounts for approximately two-thirds of the systematic variance of the tests of speech perception, and (b) a smaller component (accounting for one-third of the systematic variance of the speech perception tests) mainly representing a general performance decrement due to reduced mental efficiency, which is indicated by a general slowing of performance and a reduced memory capacity. Although both components are correlated with age, it was found that the balance between auditive and cognitive contributions to speech perception performance did not change with age.

Aged↗

PubMed1999

Neuropsychologic outcome after deep hypothermic circulatory arrest in adults.

INTRODUCTION: Pediatric patients undergoing prolonged periods of deep hypothermic circulatory arrest have been found to experience long-term deficits in cognitive function. However, there is limited information of this type in adult patients who are undergoing deep hypothermic circulatory arrest for thoracic aortic repairs. METHODS: One hundred forty-nine patients undergoing elective cardiac or thoracic aortic operations were evaluated preoperatively; 106 patients were evaluated early in the postoperative period (EARLY), and 77 patients were evaluated late in the postoperative period (LATE) with a battery of neuropsychologic tests. Seventy-three patients had routine cardiac operations without deep hypothermic circulatory arrest, and 76 patients with deep hypothermic circulatory arrest were divided into 2 subgroups: those with 1 to 24 minutes of deep hypothermic circulatory arrest (n = 36 patients) and those with 25 minutes or more of deep hypothermic circulatory arrest (n = 40 patients). The neuropsychologic test battery consisted of 8 tests encompassing 5 domains: attention, processing speed, memory, executive function, and fine motor function. Data were normalized to baseline values, and changes from baseline were analyzed by analysis of covariance, multivariate logistic regression, and survival functions. RESULTS: In all domains, poor performance or inability to be tested EARLY were significant predictors of poor performance LATE (odds ratio, 5.27; P <.01). Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were significant predictors of poor performance LATE for the memory and fine motor domains. Deep hypothermic circulatory arrest of 25 minutes or more (odds ratio, 4. 0; P =.02) was a determinant of prolonged hospital stay (>21 days). CONCLUSION: Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were associated with memory and fine motor deficits and with prolonged hospital stay.

Age Factors↗

PubMed1988

Quantitative immunocytochemistry using an image analyzer. I. Hardware evaluation, image processing, and data analysis.

In this review we describe how video-based image analysis systems are used to measure immunocytochemically labeled tissue. The general principles underlying hardware and software procedures are emphasized. First, the characteristics of image analyzers are described, including the densitometric measure, spatial resolution, gray scale resolution, dynamic range, and acquisition and processing speed. The errors produced by these instruments are described and methods for correcting or reducing the errors are discussed. Methods for evaluating image analyzers are also presented, including spatial resolution, photometric transfer function, short- and long-term temporal variability, and measurement error. The procedures used to measure immunocytochemically labeled cells and fibers are then described. Immunoreactive profiles are imaged and enhanced using an edge sharpening operator and then extracted using segmentation, a procedure which captures all labeled profiles above a threshold gray level. Binary operators, including erosion and dilation, are applied to separate objects and to remove artifacts. The software then automatically measures the geometry and optical density of the extracted profiles. The procedures are rapid and efficient methods for measuring simultaneously the position, geometry, and labeling intensity of immunocytochemically labeled tissue, including cells, fibers, and whole fields. A companion paper describes non-biological standards we have developed to estimate antigen concentration from the optical density produced by antibody labeling (Nabors et al., 1988).

Animals↗

PubMed2005

Measuring automatic retrieval: a comparison of implicit memory, process dissociation, and speeded response procedures.

Using the stem completion task, we compared estimates of automatic retrieval from an implicit memory task, the process dissociation procedure, and the speeded response procedure. Two standard manipulations were employed. In Experiment 1, a depth of processing effect was found on automatic retrieval using the speeded response procedure although this effect was substantially reduced in Experiment 2 when lexical processing was required of all words. In Experiment 3, the speeded response procedure showed an advantage of full versus divided attention at study on automatic retrieval. An implicit condition showed parallel effects in each study, suggesting that implicit stem completion may normally provide a good estimate of automatic retrieval. Also, we replicated earlier findings from the process dissociation procedure, but estimates of automatic retrieval from this procedure were consistently lower than those from the speeded response procedure, except when conscious retrieval was relatively low. We discuss several factors that may contribute to the conflicting outcomes, including the evidence for theoretical assumptions and criterial task differences between implicit and explicit tests.

Analysis of Variance↗

PubMed1989

Cognitive disturbances in patients with relapsing remitting multiple sclerosis.

The performance of 42 patients with relapsing remitting (RR) multiple sclerosis was compared with that of 24 age-, education-, and gender-matched control subjects on a battery of neuropsychological tests known from previous studies to be sensitive to the impairments of patients with chronic progressive (CP) multiple sclerosis. Like CP patients, RR patients exhibited deficits on tests of information-processing speed, verbal fluency, and problem solving, and on recall measures of anterograde and remote memory. Although a few patients were mildly dysnomic, the RR patients were not generally impaired on visual confrontation naming and they did not exhibit perseverative responding on verbal fluency measures. The pattern of neuropsychological deficits exhibited by RR patients closely approximates the profile observed in other subcortical dementias and does not contain the features of cortical dementia evident in some CP patients. The impairment of RR patients on cognitive tests were less severe than those observed in CP patients in our previous studies. Differences in the age of patients in the CP and RR groups did not account for group differences in the severity of cognitive impairments, but differences in disease duration or severity of disability, as well as disease course, could explain why CP patients exhibit more serious cognitive disturbances than RR patients.

Adult↗

PubMed1992

Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Adult↗

PubMed1995

General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson's disease.

OBJECTIVE: To contrast the neuropsychological profiles of Parkinsonian patients, before and after fetal ventral mesencephalic tissue transplantation. DESIGN: Case series of personally examined patients. SETTING: Patients were evaluated by neurologists, neurosurgeons, and neuropsychologists as outpatients at a university hospital. PATIENTS: Fetal mesencephalic tissue was implanted in the right caudate nucleus of three patients and both nuclei of one patient. These patients were evaluated prior to surgery and at 12, 24, and 26 months postoperatively. RESULTS: Factor analysis of the test battery identified four statistically orthogonal test clusters. No statistically significant changes were identified postoperatively for clusters assessing verbal cognitive ability, nonverbal cognitive ability, and information-processing speed. An improvement of verbal memory cluster index was observed 12 months after surgery, and the improvement reached the level of statistical significance at 24 months after surgery. However, the verbal memory of all patients declined between 24 and 36 months after surgery. CONCLUSIONS: Fetal tissue transplantation to one or both caudate nuclei did not permanently arrest cognitive dysfunction. Although there is some evidence of improved cognitive ability after transplantation, it is improbable that normal cognitive function can be restored by this procedure because the impairments of cognitive ability associated with Parkinson's disease do not appear to originate solely from dopamine deficiency.

Adult↗

PubMed1995

The relationship of neuropsychological functioning to quality of life in epilepsy.

OBJECTIVE: To examine the relationship of objectively assessed cognitive functioning to self-reported quality of life. DESIGN: Correlational, multiple regression, and factor analytic comparisons of a new self-report quality of life inventory with neuropsychological tests of cognition and mood. SUBJECTS: Two hundred fifty-seven patients with epilepsy. SETTING: Twenty-five epilepsy centers and neurology clinics across the United States. MEASURES: A recently developed self-report (ie, Quality of Life in Epilepsy-89 inventory) and objective tests of memory, verbal abilities, spatial functions, psychomotor and cognitive processing speed, cognitive flexibility, and mood. RESULTS: Factors that assessed mood, psychomotor speed, verbal memory, and language correlated significantly with selected scales of the Quality of Life in Epilepsy-89 inventory (P < .0001) and were predictive of overall quality of life (P < .002 to P < .0001). The mood factor showed the highest correlations (r = -.20 to r = -.73) and was the strongest predictor of quality of life in regression analyses (46.7% explained variance, P < .0001). CONCLUSIONS: Mood may be adversely affected by diminished quality of life, or perceived quality of life may be affected by mood disturbance. Quantitative quality of life assessments can be used in conjunction with formal neuropsychological testing of mood and cognition when evaluating patients with epilepsy.

Adult↗