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On the relative role of inhibition in age-related working memory decline.

In this cross-sectional study, the mediating role of inhibition relative to speed in age-related working memory decline on different tasks was investigated. It was hypothesized that the role of inhibition is marginal or absent in a relatively "passive" or simple working memory task, but present in a relatively "active" or complex task in which the processing, rather than the storage capacity of working memory, is addressed. This hypothesis was tested with a structural equation model that was fitted on a subsample (N = 213) of the Maastricht Aging Study (MAAS). The first trial of the Verbal Learning Test (VLT) served as the passive test and the Self-Paced Auditory Serial Addition Task (SPASAT) as the active test. Results showed that the role of inhibition was absent in predicting VLT performance, whereas it was comparable to the role of speed in predicting SPASAT performance. These findings suggest a relative, task-dependent role of inhibition in explaining age-related memory decline.

Adult↗

Neuropsychological significance of anosmia following traumatic brain injury.

OBJECTIVES: To investigate the incidence of anosmia following traumatic brain injury (TBI) using a standardized instrument and to test hypotheses that post-TBI anosmics perform significantly more poorly than do post-TBI normosmics on measures of executive skills and functional outcome. DESIGN: Prospective quasi-experimental between-groups design. PARTICIPANTS: Sixty-eight adults diagnosed with TBI. SETTING: Brain injury rehabilitation program based at a Midwestern medical center. MAIN OUTCOME MEASURES: University of Pennsylvania Smell Identification Test (UPSIT), selected neuropsychological measures of executive skills, the Disability Rating Scale (DRS), and the Community Integration Questionnaire (CIQ). RESULTS: Forty-four subjects (65%) demonstrated impaired olfaction; only 13 (30%) acknowledged smell dysfunction. Anosmic and normosmic groups did not differ in demographics, IQ, chronicity, or admission Glasgow Coma Scale (GCS). Anosmics had longer coma (P =. 01), more severe deficits in complex attention (Trailmaking Test, Part B, P =.01), new learning/memory (California Verbal Learning Test Trial V [CVLT-V], P =.001), and problem solving (Wisconsin Card Sorting Test [WCST], P =.001), leading to greater functional impairment (Disability Rating Scale [DRS], P =.003). No differences emerged on the CIQ. CONCLUSIONS: Anosmia is a common sequela of TBI, although only a minority of patients are aware of this deficit. Further, anosmics demonstrated greater impairment in a variety of frontal-lobe mediated executive functions, as well as greater functional disability.

Adult↗

Antipsychotic drug treatment in the prodromal phase of schizophrenia.

OBJECTIVE: The safety and tolerability of short-term treatment with a low dose of risperidone was evaluated in adolescents with prodromal symptoms and a family history of schizophrenia. METHOD: Four prodromal high-risk adolescents and six first-episode patients with schizophrenia were treated with average doses of 1.0 and 1.8 mg/day of risperidone, respectively, in an 8- to 12-week open-label trial. RESULTS: No significant treatment-related adverse events were noted. Severity of thought and behavior disturbance ratings declined by about 30%; performance on a test of verbal learning improved by about 100% during treatment in both prodromal and first-episode patients, changes that achieved statistical significance despite the small group sizes. CONCLUSIONS: These findings are preliminary and should not be used to guide health care decisions at this time. Randomized controlled trials are needed to determine whether antipsychotic drug treatment of prodromal patients can delay or prevent onset or attenuate the clinical course of schizophrenia.

Adolescent↗

Short-term monitoring of cognitive functions before and during the first course of treatment.

PURPOSE: Side effects of chemotherapy on cognitive functions in older patients have rarely been investigated. Addressing this lack of research, the present study evaluated cognitive functions in older cancer patients. METHODS: A total of 130 younger (n=59; age<60) and older (n=71; age>or=60) cancer patients with hematological disease or cancer of the intestinal tract took part in the study. To explore short-term effects of chemotherapy, a group of patients assessed before the start of chemotherapy was compared with patients who already received their first course of chemotherapy. RESULTS: Cognitive impairments of verbal learning, word fluency, and memory were observed following the first few days after treatment onset. Older patients showed stronger memory impairments after start of chemotherapy than younger cancer patients. Additionally, depression was neither associated with short-term effect of chemotherapy nor with age. CONCLUSIONS: The results suggest that chemotherapy has negative short-term effects on some cognitive functions. But age-dependent effects were only found for memory.

Adult↗

Proton magnetic resonance spectroscopy in anorexia nervosa: correlations with cognition.

The aim of this study was to investigate the relationship between cognitive impairment and cerebral metabolites in patients with anorexia nervosa (AN). N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), choline-containing compounds, glutamate/glutamine (Glx) and myoinositol were measured by proton magnetic resonance spectroscopy (H-MRS) of the left prefrontal cortex. Compared with healthy controls, AN patients displayed a significantly poorer performance in verbal learning and in attentional and executive tasks. Performance in the divided attention task was correlated with NAA and Cr in the dorsolateral prefrontal cortex, while executive functioning and depressive symptomatology were associated with Glx levels in the anterior cingulate. Our results provide evidence for cognitive impairment in AN patients which is associated with cerebral metabolism in the prefrontal cortex.

Adult↗

Neuropsychological deficits associated with antiphospholipid antibodies.

Neurologic events associated with antiphospholipid antibodies (aPAs) include transient ischemic attack, stroke, and vascular dementia in individuals much younger than is typically observed with these disorders. The present study evaluated 27 non-elderly adults with aPAs but without concurrent disease processes or history of neurologic event and 27 age- and education-matched controls. MANOVA (p <.01) indicated group differences in executive functioning, verbal learning and memory, and visuospatial ability. In contrast, gross attentional processes and fine motor skills appeared unaffected by the <?Pub Caret>syndrome. Moreover, the frequency of impaired neuropsychologic performance was greater among individuals with aPAs than among controls (p <.01). The presence of cognitive deficits in otherwise asymptomatic patients with aPAs indicates a preclinical phase of neurologic involvement and may prove to be the most sensitive markers of the syndrome.

Antibodies, Antiphospholipid↗

A comparison of the effects of lorazepam with those of propranolol on experimentally-induced anxiety and performance.

In a double-blind cross-over study the effects of propranolol (80 mg) and of lorazepam (1 or 2.5 mg) were assessed in normal student volunteers using a number of performance tests and mood-rating and bodily symptom questionnaires. Drug effects on experimentally-induced anxiety were also studied. The high dose of lorazepam impaired performance in digit-symbol substitution, symbol copying and verbal learning tests, and increased subjects' ratings of dizziness. Both lorazepam and propranolol increased simple reaction time. Lorazepam but not propranolol increased ratings of sedation. Although the stressor increased subjects' ratings of anxiety, neither drug altered anxiety ratings. Propranolol decreased and lorazepam increased subjects' pulse. These changes were not reflected in subjects' self-ratings - lorazepam caused a reduction in ratings of palpitations. The results suggest that if administered acutely, neither drug is beneficial in the treatment of short-term anxiety associated with intellectual stress.

Adult↗

Intelligence, memory, and handedness in pedophilia.

A sample of 473 male patients with pedophilia (assessed by the patients' sexual history and penile response in the laboratory to standardized, erotic stimuli) or other problematic sexual interests or behaviors received brief neuropsychological assessments. Neuropsychological measures included a short form of the Wechsler Adult Intelligence Scale--Revised (D. Wechsler, 1981), the Hopkins Verbal Learning Test--Revised (R. H. B. Benedict, D. Schretlen. L. Groninger. & J. Brandt, 1998), the Brief Visuospatial Memory Test--Revised (R. H. B. Benedict, 1997), and the Edinburgh Handedness Inventory (S. M. Williams, 1986). Pedophilia showed significant negative correlations with IQ and immediate and delayed recall memory. Pedophilia was also related to non-right-handedness even after covarying age and IQ. These results suggest that pedophilia is linked to early neurodevelopmental perturbations.

Adult↗

Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex.

Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.

Adolescent↗

Routes to actions and their efficacy for remembering.

Four experiments focused on the influence that different controls of actions have on memory for these actions. A verbal-to-action task in which subjects had to perform actions on verbal command was distinguished from a movement-to-action task in which subjects had to perform the same action that a model had shown (imitation). We expected free recall to be worse for the imitation condition than for the enactment-on-command condition. The following rank order of recall performances was observed: verbal learning << perceiving the model = imitating the watched model < performing on command = performing on command in addition to perceiving the model. The less pronounced effect of imitation on memory is explained by the fact that subjects in this condition could directly use the information provided by perception for enactment without selection and detailed planning of motor actions. In contrast, subjects in the command-to-action condition had to look up the "motor program". The inefficiency of using two modalities, i.e. perception and action, as compared to using only one is explained by the redundancy of encoded information in the visual and "motor" modality.

Adult↗

Longitudinal changes in verbal memory in older adults: distinguishing the effects of age from repeat testing.

OBJECTIVE: To characterize the relationship between age-related memory change and repeat testing using serial administrations of the California Verbal Learning Test (CVLT) in 385 nondemented Baltimore Longitudinal Study of Aging participants aged 55 and older with two or more memory assessments. METHODS: The authors investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of learning and interference, short- and long-delay free and cued recall, and recognition hits in separate mixed-effects regressions. RESULTS: The authors found cross-sectional effects of age (p < or = 0.001) and sex (p < or = 0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. Longitudinal age changes were documented across total learning and long-delay free and cued recall regardless of baseline scores (p < or = 0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on Trial 5, short-delay cued recall and recognition hits (p < or = 0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short- and long-delay recall such that younger baseline age was associated with improvement over time whereas older baseline age was associated with decline over time. CONCLUSION: Longitudinal declines in CVLT performance exist in normal aging and are influenced by baseline age. Furthermore, failure to account for the influence of repeat testing with aging may decrease sensitivity to detect pathologic decline.

Age Factors↗

Ecstasy (MDMA) exposure and neuropsychological functioning: a polydrug perspective.

Ecstasy (MDMA) is a popular drug that can act as a selective serotonin neurotoxin in several species. The goal of the present study was to examine the relationship between ecstasy exposure and cognitive functioning after controlling for other drug use and demographic variables. Furthermore, we assessed whether gender was a moderator of the relationship between cognitive functioning and ecstasy use. Data were collected from 31 men and 34 women with a wide range of ecstasy use (17 marijuana users with no ecstasy use and 48 ecstasy users ranging from low to heavy use). Participants were interviewed and administered a battery of neuropsychological tests. The primary finding was that ecstasy exposure was significantly related to poorer verbal learning and memory ability in a dose-dependent manner, while no such relationship was observed between ecstasy exposure and executive functioning or attentional ability. Gender was found to significantly moderate the relationship between ecstasy consumption and design fluency. These results suggest primary memory dysfunction among abstinent recreational ecstasy users. This finding is consistent with reports of hippocampal vulnerability, particularly among heavy users.

Adolescent↗

Characteristic patterns of verbal memory function in patients with Huntington's disease.

Various aspects of verbal memory in patients with Huntington's disease (HD) were studied using the California Verbal Learning Test (CVLT). We tested if the level and interplay between 5 parameters of different memory mechanisms and processes were sufficiently specific to allow acceptable discrimination between patients with HD, patients with Parkinson's disease (PD), and patients without known CNS disease or injury. The HD-patients were characterized by a deficit in acquisition, elevated rates of recall errors and increased use of a passive learning strategy. Preserved aspects were shown in retention over time, interference effects and recognition relative to recall. Employing multivariate classification and validation techniques, the 5 CVLT-features demonstrated good separability between the HD-patients and the control patients. Qualitative similarities between subgroups were suggested, but more disease-specific data seemed necessary in further studies. A number of findings suggested a defect in the active organization of items to be encoded and recalled in HD. Similar findings in the PD-group might indicate that this trait is common in several types of 'subcortical dementia'.

Adult↗

Familial cognitive deficits in schizophrenia.

Susceptibility to schizophrenia is considered familial, but the mechanism for transmission has not been found. Since widespread cognitive deficits have been found in patients with schizophrenia, several of these have been proposed as candidate familial endophenotypes that may or may not be predictive of who develops the illness. The current study examines these candidates in individuals from 32 families with at least 2 members having the diagnosis of chronic schizophrenia and normal comparison subjects using an extensive neuropsychological battery. Consistent with previous literature, family members with schizophrenia were significantly impaired on all measures compared with controls. Well relatives demonstrated significantly worse performance on a measure of verbal learning, delayed visual recall, perceptual-motor, and pure motor speed. Expressive and receptive language, but not other functions, were highly correlated within both concordant for schizophrenia and discordant sibling pairs, suggesting that they are familial vulnerability endophenotypes, but not predictive of whom becomes ill. On the other hand, some measures of perceptual-motor, pure motor speed, and frontal/executive functioning were significantly correlated in concordant, but not discordant pairs. These latter correlations suggest that some cognitive measures may be genetically related to the illness.

Adult↗

Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study.

RATIONALE: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. OBJECTIVES: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy ((31)P-MRS) before and after citicoline treatment. METHODS: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a (31)P-MRS scan at baseline and following 6 and 12 weeks of treatment. RESULTS: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters ( P=0.008), including an 11.6% increase in glycerophosphoethanolamine ( P=0.002) and a 5.1% increase in glycerophosphocholine ( P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. CONCLUSIONS: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.

Administration, Oral↗

Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging.

OBJECTIVE: Neurocognitive dysfunction is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Studies using magnetic resonance imaging (MRI) have demonstrated that new focal brain lesions can occur after coronary artery bypass grafting (CABG), even in patients without apparent neurological deficits. Diffusion-weighted MRI is superior to conventional MRI and allows for sensitive and early detection of ischemic brain lesions. We prospectively investigated cerebral injury early and 3 months after CABG using diffusion-weighted MRI and related the findings to clinical data and neurocognitive functions. METHODS: Twenty-nine patients [67.6+/-8.6 (52-85) years, 5 females] undergoing elective CABG with CPB were examined before surgery, at discharge and 3 months after surgery. A battery of standardized neuropsychological tests and questionnaires on depression and mood were administered. Conventional and diffusion-weighted MRI of the brain was performed and new lesions were analyzed. Clinical characteristics, neuropsychological test performance and radiographic data were collected and compared. RESULTS: There was no major neurological complication after CABG. Thirteen patients (45%) exhibited 32 new ischemic lesions on postoperative diffusion-weighted MRI. The lesions were small, rounded and equally dispersed in both hemispheres. Eight patients had at least two lesions. At discharge, significant deterioration of neuropsychological performance was observed in 6 of the 13 tests compared to baseline assessment. By 3 months postoperatively, 5 of the 6 tests returned to preoperative levels. Verbal learning ability, however, remained impaired. The presence of new focal brain lesions was not associated with impaired neuropsychological performance. There was also no correlation between clinical variables, intraoperative parameters and postoperative complications and MRI findings. CONCLUSIONS: Although neurocognitive decline after CABG is mostly transient, memory impairment can persist for months. New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline.

Aged↗

Relationship between dissociative symptomatology and declarative and procedural memory in adolescent psychiatric patients.

The purpose of this study was to examine the relationship between dissociative symptomatology and declarative and procedural memory. Subjects were 41 consecutively admitted adolescent psychiatric patients, 13 to 19 years old. Each subject completed the Adolescent Dissociative Experiences Scale (A-DES). Declarative memory was assessed by the California Verbal Learning Test and procedural memory by the Tower of Toronto puzzle. All subjects were controlled for IQ and severity of psychiatric illness. Data analysis was done by multiple regression. Multiple regression analysis revealed a model in which 71% variance of the A-DES scores was explained by psychiatric illness and specific memory variables. This study confirms a strong interrelationship between clinical dissociation and severity of psychiatric illness. Moreover, clinical dissociation seems to be associated with specific memory dysfunctions, indicating that dissociation exerts an impact on basic information processing.

Adolescent↗

Neuropsychological correlates of electroencephalograms in children with epilepsy.

INTRODUCTION: This study examined the degree to which neurophysiological activity on routine clinical EEG is associated with neuropsychological deficiencies in children with epilepsy. METHODS: Ninety-five children with epilepsy (58 chronic, 37 recent-onset; mean age = 10.41 years, S.D. = 2.87 years; mean age at onset = 5.86 years, S.D. = 3.46 years) completed a neuropsychological battery. Neurophysiological data were collected from the most recent EEG. RESULTS: In the recent-onset sample, no neuropsychological scores were related to any EEG variable. In the chronic sample, however, presence of slow-wave activity was related to memory impairment (p < 0.01). Post-hoc analyses on other neuropsychological measures showed localization of epileptiform activity (EA) might be related to verbal learning. DISCUSSION: Children with slow-wave activity on EEG might be at increased risk for developing neuropsychological deficits. When these abnormalities are observed on a child's EEG, closer monitoring of cognitive and academic functioning seems warranted. Differences between these findings and past research suggest that conclusions drawn from adult surgical studies cannot be generalized to pediatric patients, especially recent-onset samples, without qualification. Differences between the recent-onset and chronic samples in this cross-sectional study raise the possibility that neurophysiological abnormalities have a cumulative effect on cognitive development.

Adolescent↗