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PubMed2006

Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury.

Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.

Animals↗

PubMed2006

A dopamine agonist, pramipexole, and cognitive functions in Parkinson's disease.

The cognitive performance of 55 non-demented idiopathic Parkinson's disease (PD) patients treated with levodopa alone or receiving dopamine agonist pramipexole as add-on therapy to levodopa was evaluated in the present study during 6 months of treatment. Neuropsychological tests were administered two times. In the first assessment to differentiate test sensitive to cognitive changes typical for PD control group was also assessed. After 6 months of treatment PD patients were retested only with tests that differentiate them from control group. Compared to controls PD patients showed inferior performance on Stroop Interference test, Trail Making test, letter fluency and Hooper Visual Organization Test. No statistically significant differences between two groups and first and second neuropsychological assessment were found. Present findings indicate that pramipexole as add-on therapy to levodopa is safe in non-demented PD patients in terms of the effect on cognitive performance.

Adult↗

PubMed2004

Program to improve cognitive functioning in patients with schizophrenia: reflections.

Cognitive dysfunction in patients who suffer from schizophrenia is a major clinical problem. For such patients, the neurobiological cause(s) for the cognition deficits are not clear. Treatments with high doses of compounds that work at the coagonist site of the NMDA receptor have demonstrated that some degree of improvement can be elicited in patients. Thus, the NIMH effort to delineate the clinical responses that would allow new drugs to be registered for this use is very timely. Significant credit is due Dr. Steven Hyman and his colleagues for stimulating this bold initiative. Many problems remain to be solved to accomplish the goal. This article articulates a few such problems.

Antipsychotic Agents↗

PubMed2003

Dopamine and cognitive function.

PURPOSE OF REVIEW: Although the cognitive deficits of idiopathic Parkinson's disease are now relatively well known, their neuropsychological and neurobiological basis are still discussed. RECENT FINDINGS: As well as recent findings on cognitive changes and their underlying mechanisms, we will review new approaches concerning the effects of levo-dihydroxyphenylalanine, those of deep-brain stimulation and recent developments on personality disorders. SUMMARY: Future research directions concern the relative influence of the striatofrontal loops in cognition and personality, and the respective contribution of subcortical and cortical lesions or dysfunctions, both in dementia and in specific cognitive and personality changes.

Brain Chemistry↗

PubMed1990

Cognitive functions in adult Down's syndrome.

Cognitive profiles of performances were obtained from a selected group of adult Down syndrome (DS) subjects (n = 20; mean age: 34.5 years; s.d.: 7.7) by means of an ad hoc neuropsychological battery. With the aim of examining, from a neuropsychological point of view, the modifications that increasing age produces in this group of patients, cognitive performances of younger DS subjects (mean age: 28 years; s.d.: 4.77) were compared with analogous performances obtained by the older ones (mean age: 39.8 years; s.d.: 5.11). Subsequently, to clarify qualitative aspects of cognitive patterns in the subgroups of young and old DS subjects, two different groups of control patients were utilised. Neuropsychological data collected from a group of adult mentally retarded subjects were compared with cognitive performances demonstrated by young DS subjects, while the old group of DS subjects was analyzed in comparison with a group of patients affected by initial form of Alzheimer disease (AD). Altogether, the results of our study do not seem to support, from a neuropsychological point of view, the hypothesis that mental decline observed in DS subjects reproduces the cognitive patterns of impairment observed in AD patients.

Adult↗

PubMed2005

Cognitive functions in relation to MRI findings 30 years after traumatic brain injury.

OBJECTIVE: The aim of the study was to relate cognitive effects of a remote traumatic brain injury (TBI) to MRI findings and severity of injury. METHOD: Sixty-one patients were assessed on average 30 years after a TBI of variable severity. A comprehensive cognitive test battery was used to evaluate memory, executive functions and cognitive overall impairment. Multiple regression analyses were used to examine the relationships between cognitive variables and MRI volumetric findings (the volumes of the hippocampus and the lateral ventricles) and local contusions on MRI. Also, the effect of injury severity on cognitive outcome was evaluated. RESULTS: Reductions in hippocampal volumes and lateral ventricular enlargement were significantly associated with impaired memory functions, memory complaints and executive functions. Of the MRI parameters used, the best predictor for cognitive outcome was the volume of the lateral ventricle. There was only a modest relationship between severity of injury and cognitive performance. CONCLUSIONS: The results show that long-term memory impairments after TBI are associated with MRI volumetric measures. This suggests that the degree of diffuse injury leading to atrophic changes is prognostically more important than the initial severity of TBI.

Adult↗

PubMed2006

Effects of growth hormone on cognitive function.

Whether growth hormone deficiency (GHD) and/or treatment in childhood and adolescence influences cognitive outcome in children with GHD or girls with Turner syndrome (TS) is controversial. Previous studies also suggest that quality of life (QoL) is reduced in adults with GHD, particularly in the areas of social isolation and fatigue. Baseline QoL scores were significantly lower in patients with GHD than in the general population of the same age, gender, and nationality. Unfortunately, few data are available describing QoL in children with GHD. TS is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal intelligence quotients) and impaired visual-spatial and/or visual-perceptual abilities. This study evaluated the effects of GH treatment on neurocognitive function in girls with TS who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of GH treatment on final adult height. Treatment duration ranged from 1 to 7 years. The major result of this study was the absence of GH treatment effects on cognitive function in girls with TS. GHD and/or treatment in childhood and adulthood influences cognitive and/or QoL outcomes in some but not all studies. This study did not support a role for GH in influencing the characteristic nonverbal neurocognitive deficits associated with TS. However, evaluation of QoL should be a part of the routine clinical management of patients with GHD or TS.

Adolescent↗

PubMed1999

The influences of age and caffeine on psychomotor and cognitive function.

RATIONALE: The response to caffeine is affected by a number of factors, including age. Older subjects may be more sensitive to the objective effects than younger but report fewer subjective effects. OBJECTIVE: This study assessed the influence of age on the effects of caffeine on a variety of psychomotor, cognitive and subjective tests. METHODS: Forty-eight healthy subjects, male and female, were recruited, 24 in the age range 20-25 and 24 in the range 50-65 years. All subjects were regular moderate caffeine drinkers and were not withdrawn from caffeine before entry to the study. A double-blind parallel group design was used with two groups of 12 subjects in each age range. One group in each age range received placebo and the other 250 mg caffeine B.P. A range of tests was used to assess psychomotor, cognitive and subjective functioning before and 1 h post-treatment. RESULTS: Before treatment, young subjects generally performed better than older on psychomotor and cognitive tests. On the subjective tests, however, older subjects rated themselves as more alert and less tired than the younger ones. After placebo, performance and alertness improved in the younger group but declined in the older. After caffeine there were improvements in psychomotor performance and cognitive functioning in both groups, particularly in offsetting declining performance over time in the older subjects. It also produced subjective improvements in alertness. One factor to emerge was that on most assessments older subjects were better earlier in the day whereas in younger subjects performance did not show the same magnitude of decline throughout the day. CONCLUSIONS: Caffeine induced small but significant improvements in vigilance and psychomotor performance.

Adult↗

PubMed2006

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.

Aged↗

PubMed2006

Single-trial EEG-fMRI reveals the dynamics of cognitive function.

Two major non-invasive techniques in cognitive neuroscience, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have complementary advantages with regard to their spatial and temporal resolution. Recent hardware and software developments have made it feasible to acquire EEG and fMRI data simultaneously. We emphasize the potential of simultaneous EEG and fMRI recordings to pursue new strategies in cognitive neuroimaging. Specifically, we propose that, by exploiting the combined spatiotemporal resolution of the methods, the integration of EEG and fMRI recordings on a single-trial level enables the rich temporal dynamics of information processing to be characterized within spatially well-defined neural networks.

Brain↗

PubMed1996

Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates.

We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age at onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD.

Adult↗

PubMed2004

Spared somatomotor and cognitive functions in a patient with a large porencephalic cyst revealed by fMRI.

To date functional magnetic resonance imaging (fMRI) has not been extensively used in presurgical evaluation of patients with intractable epilepsy. Patient S.P. presented with left frontal originating seizures, secondary to a large porencephalic cyst that encompassed much of his occipital and temporal cortex and a substantial portion of ipsilateral parietal cortex. Nevertheless, S.P. did not demonstrate any gross impairments of praxis or speech. Scalp electroencephalogram (EEG) telemetry revealed reduced background activity in the left hemisphere, an absence of identifiable normal sleep states, and confirmed the left frontal origin of his seizures with a prolonged postictal state, suggesting that the remaining cortex in S.P.'s left hemisphere did not function normally despite his apparently normal appearance. Dichotic listening results also suggested that S.P. had an atypical language representation suggestive of either bilateral or right hemisphere speech representation. Surgical intervention to remove the remaining left hemisphere cortex was a serious consideration for treatment of S.P.'s seizures. We used fMRI to evaluate whether or not the remaining cortex in S.P.'s left hemisphere supported any cognitive or motor functions. Even though the volume of cerebral cortex was severely reduced and displaced in the left hemisphere, fMRI revealed significant activation in this remaining tissue in response to motor, somatosensory, and word generation tasks. In other words, we were able to demonstrate using fMRI that the remaining tissue in S.P.'s left hemisphere continued to support some motor and cognitive functions. The possible implications of these findings in terms of functional reorganisation are discussed briefly.

Brain Diseases↗

PubMed2000

Depth electrodes in clinical neurophysiology: neuronal activity and human cognitive function.

Depth intracranial electrodes are used in medicine for the diagnosis and treatment of certain medically intractable disorders including epilepsy and parkinsonism. Electrophysiological studies including the recording of neuronal activity via depth electrodes during cognitive tasks allow the mapping of the functional significance of various brain regions for certain cognitive functions. Knowledge accumulated throughout the last several decades allows us to draw some theoretical inferences about neuronal mechanisms of human cognition. The present paper provides a selective review of studies of neuronal activity of the human brain in relation to language, verbal memory and error detection.

Brain↗

PubMed1998

Cognitive function outcomes after traumatic brain injury.

Investigations of cognitive recovery from traumatic brain injury have utilized experimental cognitive tasks, including measures of executive function and discourse processing, to elucidate specific sequelae. The scope of research, which includes brain imaging and pharmacologic intervention, could potentially enhance rehabilitation of patients with brain injury.

Brain Damage, Chronic↗

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↗

PubMed1982

Anticonvulsant drugs and cognitive functions.

Thirty-five patients with epilepsy were seen before and 3 and 6 months following changes in their anticonvulsant regimes. Patients either underwent a reduction in the number of different drugs prescribed (n = 20) or had at least one drug changed to carbamazepine (n = 15). A third group of patients was seen at the same time intervals but remained on stable anticonvulsant therapy (n = 10). On each assessment session patients performed a series of specially designed tests of cognitive and motor functions, completed rating scales of mood, had a blood sample taken for the analysis of anticonvulsant serum levels, and had their seizure frequency for the previous 3 months documented. In addition, 24 patients had a routine EEG recording made. The overall results obtained suggested that a reduction in polypharmacy and the use of carbamazepine both had beneficial effects on cognitive functioning and mood.

Adult↗

PubMed1997

Cognitive functioning and quality of life in malignant glioma patients: a review of the literature.

The state of current research in the psychosocial and neurocognitive functioning of primary brain tumor patients, particularly those with gliomas, is reviewed. Specific instruments that have been used to evaluate psychosocial and neurocognitive functioning in this population are reviewed. Suggestions are made, based on the review, of the most appropriate psychosocial and neurocognitive instruments to implement in clinical research. Finally, research pertaining to psychosocial and neurocognitive interventions is reviewed and suggestions for further research are outlined. Few studies have adequately addressed the cognitive and psychosocial functioning of brain tumor patients and have focused primarily on relatively insensitive measures of outcome, including IQ scores, performance status, and neurologic examinations. The use of well-accepted, psychometrically sound quality of life instruments and more specific tests of cognitive functioning need to be included in clinical trials since most current treatments have a limited effect on the length of survival. Thus, the main rationale for selecting a given brain tumor therapy may ultimately be related to its profile of neurotoxic side-effects and impact on quality of life.

Adult↗

PubMed1999

Evidence for an association between hookworm infection and cognitive function in Indonesian school children.

The association between helminth infection and cognitive and motor function was investigated in school-age children in Java, Indonesia. 432 children from 42 primary schools participated in the study. Children were stratified by age and sex into two age groups, 8-9 years and 11-13 years. Children infected with hookworm performed significantly worse than children without hookworm infection in 6 of the 14 cognitive or motor tests. After controlling for school (as a random effect) plus age, socio-economic status and parental education, sex, stunting (height-for-age < - 2sd), body mass index, haemoglobin concentration and the presence of A. lumbricoides and T. trichiura infections, infection with hookworm explained significantly lower scores on tests of Fluency (P < 0.01), Digit-Span Forwards (P < 0.01), Number Choice (P < 0.01), Picture Search (P < 0.03), Stroop Colour Word (P < 0.02) and Mazes (P < 0.001). In 4 of the 6-tests (Fluency, Number Choice, Picture Search and Mazes), there was a significant interaction between hookworm infection and age (P < 0.03), indicating that the association between hookworm and lower test scores increased with age. No associations were observed between hookworm infection and scores in tests of Digit-Span Backwards, Corsi-Block, Stroop Colour, Stroop Interference, Free Recall, Verbal Analogies, Bead Threading or the Pegboard (P > 0.05). Tests associated with helminths represented various functions of working memory. No significant associations between helminth infection and motor function were observed that could not be explained by chance. The results suggest that hookworm infection can have a significant adverse effect on children's working memory which may have consequences for a child's reasoning ability and reading comprehension. Although the results are only associational, the fact that differences in cognition were observed at baseline imply that preventing infection with helminths in school-age children could be of benefit.

Adolescent↗