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Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.

Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.

Child↗

Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury.

A cohort of 1022 consecutive singleton births was generated during 1986-1987 in the Faroe Islands. Increased methylmercury exposure from maternal consumption of pilot whale meat was indicated by mercury concentrations in cord blood and maternal hair. At approximately 7 years of age, 917 of the children underwent detailed neurobehavioral examination. Neuropsychological tests included Finger Tapping; Hand-Eye Coordination; reaction time on a Continuous Performance Test; Wechsler Intelligence Scale for Children-Revised Digit Spans, Similarities, and Block Designs; Bender Visual Motor Gestalt Test; Boston Naming Test; and California Verbal Learning Test (Children). Clinical examination and neurophysiological testing did not reveal any clear-cut mercury-related abnormalities. However, mercury-related neuropsychological dysfunctions were most pronounced in the domains of language, attention, and memory, and to a lesser extent in visuospatial and motor functions. These associations remained after adjustment for covariates and after exclusion of children with maternal hair mercury concentrations above 10 microgram(s) (50 nmol/g). The effects on brain function associated with prenatal methylmercury exposure therefore appear widespread, and early dysfunction is detectable at exposure levels currently considered safe.

Adult↗

Low education is a genuine risk factor for accelerated memory decline and dementia.

A relatively high prevalence and incidence of dementia have been found in population strata with low levels of education in comparison to population strata with high levels of education. However, doubt remains whether this may be an artifact of education bias in the screening tests used. To investigate this matter, we analyzed results of two Dutch population surveys in which unbiased measures of memory decline were used. In the Longitudinal Aging Study Amsterdam (n = 1774) the percentage of words retained in a verbal learning test was found to be disproportionately low in the oldest age cohort (80-85 years) with less than 11 years of education. The Amsterdam Study of the Elderly (n = 4051) found a "dose-response" relationship between education and dementia prevalence. Cross-sectional and longitudinal results showed that, in less educated people, memory decline is faster and sets in at an earlier age. These findings indicate that the relationship between dementia and education is not just an artifact of case detection methods.

Aged↗

Complex partial and secondarily generalized seizure patients: cognitive functioning prior to treatment with antiepileptic medication. VA Epilepsy Cooperative Study 264 Group.

This investigation of cognitive functioning in patients with symptomatic localization-related (partial) epilepsy prior to administration of antiepileptic medication is part of a nationwide prospective, double-blind study of drug efficacy and longitudinal changes in cognition associated with seizure disorders. Recently-diagnosed patients with complex partial or secondarily generalized tonic clonic seizures, equated for age, education and IQ, were compared with normal controls on a battery of neuropsychological tests: verbal and figural memory measures (Rey auditory verbal learning test, Rey Osterrieth complex figure), and a brief behavioral toxicity battery comprising measures of motor function, concentration and mental flexibility (Lafayette grooved pegboard, controlled word association test, Stroop, paced auditory serial addition test [PASAT]). Control subjects perform significantly better than both groups of seizure patients on several measures of motor speed/integration and memory, specifically the pegboard and the RAVLT learning (3-5) and recall trials. Secondarily generalized seizure patients show greatest impairment. They perform significantly worse than patients with complex partial seizures and control subjects on the controlled word association test and the most demanding Stroop color word trial, both measures of concentration and mental flexibility. These findings document deficits in memory as well as concentration and motor function in complex partial and in secondarily generalized seizure patients prior to treatment with antiepileptic medication.

Adult↗

Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

Adult↗

The Penn Conditional Exclusion Test (PCET): relationship to the Wisconsin Card Sorting Test and work function in patients with schizophrenia.

Performance on the Penn Conditional Exclusion Test (PCET), a new computerized measure of executive function with alternate forms, was compared with performance on the Wisconsin Card Sorting Test (WCST) in a sample of 32 patients with schizophrenia. In Analysis 1, the PCET and WCST were administered with several other standard neuropsychological measures to assess convergent and divergent validity. Results revealed that categories achieved and total errors on the PCET were closely related to analogous measures from the WCST. Divergent validity was supported through nonsignificant correlations between the PCET and measures of speeded visual sequencing, verbal learning and psychomotor speed. In Analysis 2, the relationship between the PCET, WCST and a detailed measure of vocational function, the Work Behavior Inventory (WBI), was compared. Results revealed that both executive-function measures were related to specific dimensions of work function as measured in a vocational setting. More specifically, categories achieved and total errors on both the WCST and PCET were related to measures of cooperativeness on the job. Errors on the PCET were also related to measurements of work quality and general impressions of work. These results provide the first evidence of criterion-related validity for the PCET and are part of a growing literature suggesting a relationship between performance on measures of executive function and work skills.

Adult↗

Neuroleptic dose reduction in older psychotic patients.

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropsychological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics (n = 19) or maintained on neuroleptics (n = 22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in any group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.

Age Factors↗

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia.

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.

Activities of Daily Living↗

Cognitive patterns in subtypes of schizophrenia.

AIM: Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS: The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION: This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.

Adolescent↗

Functional comparison of primacy, middle and recency retrieval in human auditory short-term memory: an event-related fMRI study.

Primacy and recency effects refer to the better performance or shorter response time on the first and last items than the middle ones of a memory list. In order to investigate its neural basis in auditory short-term memory, event-related fMRI was used to measure brain activities when subject was recalling the first, the last, or the middle items. Recalling the middle item was associated with more extensive activation in the left parietal and visual cortex, basal ganglia, and dorsal cerebellum. Recalling items from different serial positions also resulted in different activation time courses in the bilateral primary auditory cortex, left prefrontal cortex and left premotor cortex. These data indicate that the auditory cortex may serve as a transient storage or the auditory input buffer, which seems to play an important role in the primacy and recency effects.

Acoustic Stimulation↗

Surgery of the thoracic aorta using deep hypothermic total circulatory arrest. Are there neurological consequences other than frank cerebral defects?

OBJECTIVE: Deep hypothermic total circulatory arrest has reduced primary morbidity and mortality in thoracic aortic surgery. Although frank neurological deficits have been proven to be a rare complication of this technique, the rate of subtle but irreversible neuropsychological disorders remains unknown. METHODS: A total of 23 patients (15 male, 8 female) who had undergone surgery for dissection or aneurysm of the thoracic aorta using deep hypothermic total circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively. The mean follow-up was 17 months. The following psychometric tests were conducted: a computer-based test battery to assess tonic alertness and sustained attention, the trail making test (TMT part A and B), the Münchner Gedächtnistest and a verbal learning test. In addition, a cerebral dopamine D2 receptor scintigraphy (using the SPECT technique) was performed. For comparison, 10 healthy subjects were studied. RESULTS: With regard to tonic alertness, 69.6 and 30.4% were below the 50th and 10th centiles, respectively, according to age- and education-corrected standard values. The impairment in sustained attention correlated significantly with the duration of the circulatory arrest. On the tests assessing short-term memory, the patients scored 30% below their age- and education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the patients were below one and two standard deviations, respectively. Concerning speed of information processing whilst 78.3% of the patients were below the 50th and 21.7% below the 10th centile. Indicative of some persistent and functional brain alteration, the dopamine D2 receptor binding was significantly reduced when compared with healthy subjects. CONCLUSIONS: These data prove a substantial and chronic reduction of higher cognitive function in some of the patients who underwent cardiac surgery using deep hypothermic total circulatory arrest; this was accompanied by a depression of the cerebral dopamine D2 receptor binding.

Adult↗

Pain mapping during minilaparoscopy in infertile patients without pathology.

STUDY OBJECTIVE: To draw a map of pelvic pain and quantify the level of provoked pain during minilaparoscopy under local anesthesia and conscious sedation. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twenty infertile women. INTERVENTIONS: Minilaparoscopy was performed under local anesthesia and conscious sedation, and cognitive performance was evaluated with the Rey auditory verbal learning task. MEASUREMENTS AND MAIN RESULTS: The diagnostic procedure was performed with one 2-mm micrograsper and one 2-mm microprobe to evaluate the pelvis. In particular we grasped utero-ovarian ligaments; we touched, grasped, and distended fallopian tubes with blue dye; we moved the uterus with a manipulator inserted at the cervix; and we touched and grasped bowel and omentum. Level of pain was recorded on a visual analog scale. Patients had no pathologic findings, including minimal endometriosis and pelvic adhesions. The highest level of pain was recorded when we distended the tubes. No pain was elicited when we touched and grasped ovary, omentum, and bowel. In 10% of women when we stretched the tubo-ovarian ligament we provoked a minimal vagal reaction. CONCLUSION: Minilaparoscopy under conscious sedation for pelvic pain mapping in women without pain or pathology revealed consistently negative findings, validating the value of this measurement. (J Am Assoc Gynecol Laparosc 6(1):51-54, 1999)

Adult↗

Memory functions, alprazolam and exposure therapy: a controlled longitudinal study of agoraphobia with panic disorder.

Benzodiazepines (BZs) produce transient anterograde amnesia when given to normal subjects. The present longitudinal study assessed whether BZs impair memory functions in a clinically anxious group. Eighty-two agoraphobics with panic disorder were randomly allocated to one of four treatment groups resulting from a combination of two drug treatments (alprazolam or placebo) and two psychological treatments (exposure or relaxation). Of these, 38 subjects were assessed on a range of objective and subjective indices of memory and mood at three time points: before treatment, after 8 weeks of treatment and again at 24 weeks when patients had been free of medication from 5-8 weeks. Alprazolam produced pronounced impairments on a word recall task. At the 24-week medication-free follow-up, alprazolam patients were still impaired on the task compared with placebo patients. Alprazolam did not impair performance on an implicit memory task and did not affect digit span. Differences between psychological treatments emerged mainly in subjective memory effects. Findings are discussed in terms of the specificity of BZ-induced amnesia and differential tolerance to the varying effects of BZs. Implications are drawn out for the patient's ability to function optimally in daily life while taking alprazolam.

Adult↗

Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.

Aged↗

Memory and attention test performance of young and elderly subjects after retest practice.

The effects of training on two memory and two attention tasks were investigated in 24 healthy elderly and 23 young subjects. Two training periods, each consisting of four sessions, were performed, and the effects of training were assessed during two test sessions 1 week thereafter. Significant age-related effects at the pretraining test session were found for reaction times to a simple visual stimulus, retrieval time of information from long-term storage, and the speed of focusing attention. In both age groups, performance of the first two tasks was significantly improved by training; however, the age-related effect remained significant after training. In the focused attention task, the age difference at baseline disappeared after training due to an opposite learning trend in young and elderly subjects. Thus, the cognitive performance of elderly subjects could be trained to a large extent. Significant age differences, however, could be decreased only if the test performance of young subjects did not improve.

Adult↗

Long-term effects of high-dose zidovudine treatment on neuropsychological performance in mildly symptomatic HIV-positive patients: results of a randomized, double-blind, placebo-controlled investigation.

This study examined the treatment outcome of high-dose (1500 mg/day) zidovudine (AZT) on neuropsychological (NP) functioning (Trailmaking Test A & B, WAIS-R Digit Symbol, and Rey Auditory Verbal Learning Test) across a 12-month period in mildly symptomatic HIV-1 seropositive men (n = 46 at entry) enrolled in a randomized, double-blind, placebo-controlled trial (VA Cooperative Studies Program #298). Neither short-term (0-6 months) nor long-term (0-12 months) AZT administration revealed enhancement in NP performance. The results suggest that, although AZT may afford patients prophylactic benefits, protracted high-dose AZT treatment does not improve NP functioning in mildly symptomatic HIV-positive individuals.

Adult↗

Effects of retroactive and proactive interference on word list recall in schizophrenia.

Schizophrenia spectrum patients (N = 143) and healthy controls (N = 160) were administered the Rey Auditory Verbal Learning Test (RAVLT) and tests of executive functioning to directly investigate the effects of proactive interference (PI) and retroactive interference (RI) on word list recall. It was hypothesized that by virtue of the predicted preferential association between executive functioning and RI (relative to PI), patients would demonstrate increased susceptibility to RI in their ability to recall word lists. Results indicated that patients show increased susceptibility to RI relative to PI. Furthermore, this difference appeared to be related to the frontally-mediated central executive functions that were preferentially associated with RI but not PI susceptibility.

Adult↗

The serial position effect in mild and moderately severe vascular dementia.

The present study examined the serial position effect in 2 subgroups of individuals with vascular dementia (VaD). Nineteen individuals with mild VaD and 17 individuals with moderate VaD were administered the California Verbal Learning Test. Both groups were impaired on a general memory measure, and the moderately impaired group demonstrated significantly poorer recall than the mildly impaired group on the first learning trial and on total learning across trials. In addition, individuals with mild dementia demonstrated an intact primacy and recency effect, whereas individuals with moderate dementia demonstrated neither primacy nor recency effects. The latter findings are consistent with studies examining the serial position effect in other dementia populations, and suggests that the absence of primacy and recency effects in more advanced dementia may occur regardless of dementia type.

Cytidine Diphosphate Choline↗