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PubMed1993

Organic brain dysfunction and cognitive deficits in young schizophrenic patients with tardive dyskinesia.

Tardive dyskinesia (TD) has been associated with cognitive deficits, especially in older psychiatric patients on neuroleptic medication. This study investigated the relationship between presence of TD, organic brain dysfunction (OBD), and cognitive deficits in young psychiatric outpatients maintained on minimal doses of oral neuroleptics, with anticholinergics prescribed only on as-needed basis. Sixty-four patients, aged 20-39 years, were evaluated for the presence of abnormal movements, localizing and nonlocalizing physical signs, and deficits in memory, ability to shift, and sustained attention. Sixteen patients showed definite signs of TD. Significant associations were found between TD and OBD, and between cognitive deficits and OBD, but not between TD and cognitive deficits. Significant regression predictors of TD were the interaction between OBD and previous dystonia, as well as duration of neuroleptic treatment. These findings suggest that some potential risk factors for TD already identified in the literature also apply to younger patients with relatively shorter exposure to neuroleptics. However, the results indicate that the relationship between movement disorders and cognitive deficits may be more apparent in older patients.

Adult↗
PubMed2005

Temporal dissociation of components of cognitive control dysfunction in severe TBI: ERPs and the cued-Stroop task.

Cognitive control comprises two essential interactive component processes: a regulative component supporting the activation and implementation of control and an evaluative component that monitors the need for regulative control and signals when adjustments in control are necessary. Survivors of severe traumatic brain injury (TBI) experience cognitive control impairments, but the specific nature of these impairments is poorly characterized. Using event-related potentials (ERPs) acquired in the context of a trial-by-trial task-switching version of the Stroop task we temporally dissociated the regulative and evaluative processes in order to shed light on the potential roles of these components in TBI-related cognitive control impairment. Behaviorally, TBI patients showed a specific performance deficit suggestive of a failure to implement cognitive control in the service of processing conflict information. ERP findings showed that TBI patients were impaired in both the implementation of control and subsequent detection and processing of conflict. TBI patients were also impaired on a measure of working memory capacity, a measure that correlated with the ability to implement regulative control and overcome conflict. These findings suggest that patients with predominantly chronic severe TBI patients are impaired on both regulative and evaluative components of cognitive control, and may have implications for the design and evaluation of behavioral and pharmacological remediation strategies.

Adult↗
PubMed2005

The applicability and the inter-rater reliability of the Comprehensive Psychopathological Rating Scale in an elderly clinical population.

BACKGROUND: Psychopathological rating scales are developed and tested on a relatively young population. Their applicability and psychometric performance in the elderly (aged above 60-65 years) are mostly unknown. It is unknown how factors related to ageing or mild cognitive dysfunction influence the applicability and the reliability of these scales. We tested the applicability and the inter-rater reliability of the Dutch version of the Comprehensive Psychopathological Rating Scale (CPRS) on an elderly (age > 60 years) inpatient population. METHODS: The applicability and reliability (expressed by differently weighted Kappa coefficients) of the CPRS was assessed by investigating 62 consecutively referred patients in a ward for elderly patients with acute psychiatric problems that were primarily functional in nature. The results are compared with those found in a younger population. RESULTS: The applicability and reliability of the CPRS on the elderly can be categorised as sufficient to good and is comparable with results for a younger population. We did not find any specific factors influencing the practicality, or the reliability of the CPRS when applied to an elderly group of people with a mild cognitive dysfunction. CONCLUSIONS: The CPRS does not loose its clinical relevance with age, as the applicability and the reliability of the CPRS is not influenced by ageing or mild cognitive dysfunction. The CPRS can detect a broad range of symptoms and due to its psychometric properties it is a useful instrument for measuring an elderly or young population.

Age Factors↗
PubMed2003

Tolterodine and memory: dry but forgetful.

BACKGROUND: Anticholinergic drugs are known to produce or enhance cognitive deficits. Tolterodine tartrate is marketed as a bladder-selective anticholinergic drug that is reported to be free of significant cognitive adverse effects. OBJECTIVE: To describe a 46-year-old woman who had memory loss and abnormal memory test results that improved when she discontinued tolterodine therapy. RESULTS: While taking tolterodine, the patient's score on the delayed free recall portion of the Hopkins Verbal Learning Test-Revised was at the first percentile. One month after discontinuing tolterodine therapy, this test was administered a second time using an alternative form and she showed marked improvement scoring above the 75th percentile. CONCLUSIONS: Tolterodine therapy caused cognitive dysfunction in our patient. It is possible that cognitive dysfunction is a common result of tolterodine treatment, but in the absence of testing, remains undiagnosed. Alternatively, our patient may have had aberrant metabolism of this drug or an increased sensitivity as a result of incipient Alzheimer disease.

Benzhydryl Compounds↗
PubMed2005

Neurocognitive outcomes: the year in review.

PURPOSE OF REVIEW: This review is a survey of the recent literature investigating the etiology and the relative incidence of postoperative neurological and cognitive dysfunction after cardiac surgery. RECENT FINDINGS: Several studies reviewed here have employed transcranial Doppler for detection of cerebral emboli and compared results between patients undergoing beating-heart versus conventional cardiopulmonary bypass. A transcranial Doppler device ostensibly discriminating between particulate and gaseous emboli has additionally been employed, yet despite a consistently lower incidence of cerebral emboli associated with avoidance of cardiopulmonary bypass, several groups have reported similar incidences of cognitive dysfunction across these procedures, suggesting other, potentially more important, factors. Two recent studies have focused on the hazards associated with perioperative anemia in both infants and older patients, and which can result in developmental delay or profound changes in cerebral blood flow. A further study has identified an adverse interaction with postoperative hypoxia. The use of intraortic filtration for capture and removal of particulate macroemboli has been associated with a reduction in the incidence of clinically apparent central-nervous-system injury and should be further investigated. Several other studies identify pre-existing levels of central-nervous-system impairment prior to surgery, underscoring the confounding issues introduced by the failure to include a non-surgical comparator group. SUMMARY: While further evidence of cerebral embolization continues to accrue, several studies suggest that other factors may be of equal or greater importance in cognitive dysfunction. Further investigations into the role of perioperative anemia, co-incident hypoxemia and other aspects of perioperative care, e.g. hyperglycemia and postoperative hyperthermia, are warranted.

Journal Article↗
PubMedDate not supplied

Correlations of Perceived Deficits Questionnaire of Multiple Sclerosis Quality of Life Inventory with Beck Depression Inventory and neuropsychological tests.

The Perceived Deficits Questionnaire (PDQ) is a part of the Multiple Sclerosis (MS) Quality of Life Inventory that assesses self-perceived cognitive difficulties. We used baseline data from 49 MS subjects participating in a clinical trial to evaluate the correlation of the PDQ with two measures of cognitive impairment, the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test, 2nd edition (CVLT-II), total score, and one measure of depression, the Beck Depression Inventory-Amended (BDI-IA). The PDQ correlated significantly (r = 0.42; 95% confidence interval [CI], 0.15 to 0.62; p = 0.003) with the BDI-IA scores but not with either the PASAT (r = -0.22; 95% CI, -0.48 to 0.06; p = 0.2) or the CVLT-II total (r = -0.17; 95% CI, -0.43 to 0.12; p = 0.25). A subset of 38 of these subjects who scored worse than 0.5 standard deviation below the mean on the PASAT or CVLT-II received a more extensive neuropsychological battery of tests. No significant correlations were found between any of these tests and the PDQ. These results suggest that self-perceived cognitive dysfunction relates more to depression than to objective cognitive dysfunction.

Adolescent↗
PubMed2005

Relationship between cognition and work functioning among patients with schizophrenia in an urban area of India.

OBJECTIVE: Employment rates and work functioning are poor among patients with schizophrenia and are related to cognitive dysfunction. This study examined the relationship between work functioning and cognition, other clinical and demographic variables, and measures of social functioning among patients with schizophrenia in an urban area of India. METHODS: This study evaluated cognitive dysfunction and work functioning among 88 patients with chronic schizophrenia. Attention, executive function, and memory were tested with a battery of neuropsychological tests. Work and social functions were evaluated with standardized instruments. RESULTS: Fifty-nine patients (67 percent) were employed, most in a mainstream environment. Moderate to significant work dysfunction was present among 21 patients (24 percent). When multivariate analysis was performed, cognitive deficits did not relate significantly to current employment status or to level of performance at work. Negative symptoms predicted employment status, and poor social functioning predicted poor work performance. CONCLUSIONS: The relationship between work and cognitive status in schizophrenia was not as strong as has been previously reported in this population. It was speculated that social factors, such as the compelling need to be employed, a supportive work environment, and the number of years of formal education, were factors underlying the high level of work functioning in this group despite cognitive deficits.

Adult↗
PubMed2003

Cognitive impairment: a key feature of congestive heart failure in the elderly.

Congestive heart failure (CHF) has been proposed as a possible cause of cognitive dysfunction but only a few studies have directly assessed cognitive performance in CHF. The aim of the present study was to compare the cognitive patterns of patients with CHF and patients having cardiovascular diseases uncomplicated by CHF (no-CHF group). In a multicenter observational case-control study, we studied 149 hospitalized elderly CHF patients in the New York Heart Association (NYHA) class II (CHFm, m: moderate), 159 CHF patients in NYHA class III-IV (CHFs, s: severe), and 207 no-CHF patients. Patients underwent a multidimensional assessment and neuropsychological tests for the following cognitive domains: attention, visual-spatial intelligence, verbal attainment, verbal and visuo-spatial memory. Neuropsychological performances of groups were compared by multivariate analysis. Correlates of an abnormal performance on at least three neuropsychological tests were assessed by logistic regression analysis. CHFs performed worse than no-CHF patients on 4 of the 7 neuropsychological measures, the largest difference being in tests of attention and verbal learning (p < 0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001). The following qualified as independent correlates of the outcome at logistic regression analysis: CHFs group membership (Odds Ratio-OR = 2.56, 95% Confidence Interval-CI = 1.49-4.40), depression (OR = 2.37, 95% CI = 1.54-3.66), hypertension (OR = 1.88, 95% CI = 1.18-2.99). Our results demonstrate that cognitive impairment is common among CHF patients and seems to be causally related to CHF severity, depression and hypertension. The cognitive dysfunction also characterizes a relevant fraction of patients with cardiovascular diseases uncomplicated by CHF.

Aged↗
PubMed2002

Hippocampal brain amines in methotrexate-induced learning and memory deficit.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

Animals↗
PubMedDate not supplied

Effect of intracerebroventricular methotrexate on brain amines.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.

Animals↗
PubMed2001

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Adult↗
PubMed2006

Testosterone and cognitive function: current clinical evidence of a relationship.

BACKGROUND: Testosterone levels decline as men age, as does cognitive function. Whether there is more than a temporal relationship between testosterone and cognitive function is unclear. Chemical castration studies in men with prostate cancer suggest that low serum testosterone may be associated with cognitive dysfunction. Low testosterone levels have also been observed in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). This paper reviews the current clinical evidence of the relationship between serum testosterone levels and cognitive function in older men. METHODS: A systematic literature search was conducted using PubMed and EMBASE to identify clinical studies and relevant reviews that evaluated cognitive function and endogenous testosterone levels or the effects of testosterone substitution in older men. RESULTS: Low levels of endogenous testosterone in healthy older men may be associated with poor performance on at least some cognitive tests. The results of randomized, placebo-controlled studies have been mixed, but generally indicate that testosterone substitution may have moderate positive effects on selective cognitive domains (e.g. spatial ability) in older men with and without hypogonadism. Similar results have been found in studies in patients with existing AD or MCI. CONCLUSIONS: Low endogenous levels of testosterone may be related to reduced cognitive ability, and testosterone substitution may improve some aspects of cognitive ability. Measurement of serum testosterone should be considered in older men with cognitive dysfunction. For men with both cognitive impairment and low testosterone, testosterone substitution may be considered. Large, long-term studies evaluating the effects of testosterone substitution on cognitive function in older men are warranted.

Androgens↗
PubMed2004

Phase II study of alpha-tocopherol in improving the cognitive function of patients with temporal lobe radionecrosis.

BACKGROUND: Radiotherapy is an important treatment modality for brain tumors and is the standard radical treatment for nasopharyngeal carcinoma (NPC). However, the treatment is not free of side effects, and one possible neurologic sequela is the occurrence of temporal lobe radionecrosis (TLN) associated with cognitive dysfunction. Currently, there is no effective intervention to improve patients' cognitive performance. METHODS: Twenty-nine patients with TLN after radiotherapy for NPC were recruited on a voluntary basis. Among them, 19 patients (15 males and 4 females) received a megadose of alpha-tocopherol (vitamin E) (2000 international units per day) for 1 year, whereas the other 10 (5 males and 5 females) served as control patients. Their cognitive function (i.e., global cognitive ability, attention, memory, language, and executive function) was evaluated by a battery of neuropsychological tests before and after treatment. RESULTS: Significant improvement in global cognitive ability (P = 0.035) and memory (verbal: P = 0.036; visual: P = 0.007) occurred among patients in the treatment group after a 1-year medication period. In addition, the executive function of the treatment group improved significantly (P = 0.04). No difference was found between the two groups with respect to attention or language. CONCLUSIONS: The current investigation was a preliminary study on the effect of alpha-tocopherol on the cognitive function of patients with TLN after radiotherapy for NPC. In view of the absence of effective treatment for patients with cerebral radionecrosis, alpha-tocopherol has the potential to be a complementary intervention for patients with cognitive dysfunction due to TLN.

Aged↗
PubMed2000

Long-term dysfunction following diffuse traumatic brain injury in the immature rat.

Children often suffer sustained cognitive dysfunction after severe diffuse traumatic brain injury (TBI). To study the effects of diffuse injury in the immature brain, we developed a model of severe diffuse impact (DI) acceleration TBI in immature rats and previously described the early motor and cognitive dysfunction posttrauma. In the present study, we investigated the long-term functional ability after DI (150 gm/2 m) compared to sham in the immature (PND 17) rat. Beam balance and inclined plane latencies were measured daily for 10 days after injury to assess gross vestibulomotor function. The Morris water maze (MWM) paradigm was evaluated monthly up to 3 months after DI and sham injuries. Reduced latencies on the balance beam and inclined plane were observed in DI rats (p < 0.05 vs. sham [n = 10 per group]) at 24 h and persisted for 10 days postinjury. DI produced sustained MWM performance deficits (p < 0.05 vs. sham) as indicated by the greater latencies to find the hidden platform remarkably through 90 days after injury. Lastly, the brain and body weights of the injured animals were less than sham (p < 0.05) after 3 months. We conclude that a diffuse TBI in the immature rat: (a) created a consistent, marked, but reversible motor deficit up to 10 days following injury; (b) produced a long-term, sustained performance deficit in the MWM up to 3 months posttrauma; and (c) affected body and brain weight gain in the developing rat through 3 months after injury. This TBI model should be useful for the testing of novel therapies and their effect on long-term outcome and development in the immature rat.

Aging↗
PubMed2003

Tryptophan modulation and cognition.

The interest in the function of the serotonergic system in relation to cognition stems from three sources: (1) the association of depression, cognitive dysfunction and 5-HT dysregulation; (2) the association of drug-induced 5-HT dysregulation and cognitive dysfunction; and (3) the association of cognitive performance and serotonergic function per se. We performed several experiments in subjects at risk for cognitive impairment and in healthy volunteers, in which 5-HT was manipulated by means of either tryptophan depletion or tryptophan loading. The results show that tryptophan and cognitive performance are associated in a complex non-linear fashion. Dissociations are observed between cognitive functions: tryptophan depletion impairs memory consolidation but improves focussed attention; as well as between subject groups: tryptophan depletion impairs problem solving in healthy 1st degree relatives of bipolar depressed patients but improves it in healthy volunteers without such a family history. It was demonstrated that the mood- and memory effects of tryptophan-depletion were specifically mediated by the depletion of tryptophan and also that the observed memory and cognitive deficits were emotionally biased in a manner consistent with depressive symptoms. We conclude that experimental manipulations of tryptophan mediate temporal and frontal cognitive functions such as memory consolidation and working memory respectively, in an opposite manner.

Cognition↗
PubMed2006

'I think therefore I am': improving cognition.

PURPOSE OF REVIEW: In the absence of a specific treatment for dementia, the effective management of cognitive symptoms is a clinical priority. RECENT FINDINGS: Although some differences have been observed in the profile of cognitive complaints observed in subtypes of dementia, there is increasing recognition of common, interacting neurobiological causes suggesting the need to seek a common treatment applicable to all causes of cognitive deterioration. There also exists increasing interest in intervening at the level of minor cognitive dysfunction by reducing risk factors for subclinical states. SUMMARY: Pharmacological treatment of cognitive disorder is beneficial but has only temporary benefit for a subgroup of patients. Pharmacogenetics may have an important future role to play in deciding which patients may best benefit from the treatment. Low side effect therapies such as cognitive therapy and acupuncture show some benefits but their utility in combination with pharmacotherapies remains to be demonstrated. Prevention of milder forms of cognitive disorder by controlling risk factors such as hypertension and diabetes may reduce rates of more severe cognitive degeneration. Persons with cognitive dysfunction are commonly excluded from making decisions about the implementation of cognition-enhancing treatments although they wish to do so.

Cognition↗
PubMed1996

[Supratentorial gliomas: neuropsychological study of long-term survivors].

A battery of psychologic tests was administered to 32 patients, aged from 26 to 61 years, who had survived 2 years or more after treatment with surgery and radiotherapy for supratentorial gliomas (18 low grade and 14 high grade) without evidence of recurrent tumor on MRI. Two groups were identified. A first group of 17 patients had neuropsychologic scores similar to estimated premorbid level (group I). A second group of 15 patients had abnormal neuropsychologic scores, lower that their estimated premorbid level (group II). In comparison with "normal" patients, those with abnormal neuropsychologic scores were older at the time of treatment, had a lower post-operative Karnofski Performance Status, a longer delay between surgery and the date of the tests and more often had left sided lesions. Comparison of Karnofski Performance Status between the post-operative time point and the date of neuropsychological evaluation did not show a significant change over time in groups I and II except in 3 patients who experienced progressive deterioration. Vigorous treatment of gliomas with surgery, radiotherapy and sometimes chemotherapy does not induce a substantial cognitive dysfunction in about half of the long term survivors (53%). Cognitive dysfunction is identified in the other half that could be related to post-operative sequelae (due to the tumor itself or to surgery) and/or to radiotherapy- and chemotherapy-induced delayed toxicity.

Adult↗