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Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

Brain↗

Attention and memory dysfunctions in mild multiple sclerosis.

This study investigated the relationship between clinical symptoms and cognitive dysfunction in multiple sclerosis. Cognitive dysfunction and visual evoked potentials (VEPs) were studied in patients free of physical disability and mildly to moderately disabled patients with multiple sclerosis (MS). Disability-free patients (EDSS < or = 1.5; n = 13), mildly to moderately disabled patients (EDSS ranging from 2 to 6; n = 13) and a healthy matched control group (n = 16) were examined with respect to attention, verbal and nonverbal memory and early visual processing (VEPs). Disability-free patients showed mild impairments on phasic alertness and divided attention. Deficits were more pronounced in mildly to moderately disabled patients who were additionally impaired with respect to non-verbal memory. Despite adequate visual acuity, one half of all patients showed abnormal VEP latencies for both eyes at the same time. The findings suggest that cognitive deficits are already present in multiple sclerosis even in the absence of physical disability. Even with normal visual acuity, perceptual impairments should be considered as part of the CNS affection.

Adult↗

[Postoperative cognitive deficits].

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Cognition Disorders↗

Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery.

OBJECTIVE: Although coronary artery bypass grafting (CABG) has been shown to improve quality of life and functional capacity for many patients, recent studies have demonstrated that a significant number of patients exhibit impairment in cognitive function immediately following surgery and beyond. We sought to determine the impact of this postoperative cognitive dysfunction on quality of life (QOL) and to characterize the dysfunction from the patient's perspective. METHODS: With Institutional Review Board (IRB) approval and written informed consent, 732 patients at Duke University Hospital undergoing CABG were enrolled. Five hundred fifty-one (75%) completed baseline, 6-week, and 1-year neurocognitive tests and psychometric measures designed to assess QOL. Neurocognitive status was assessed by a composite cognitive index score representing the mean of the scores in four cognitive domains. Change in QOL was assessed by subtracting baseline from 1-year scores for each of 10 QOL measures. The association between QOL and cognitive dysfunction was investigated using multivariable linear regression analysis. RESULTS: Cognitive decline limited improvement in QOL, with substantial correlation between change in cognition and change in QOL. One-year QOL measures are associated with both 6-week and 1-year change in cognition (Instrumental Activities of Daily Living, p < .0001; Duke Activity Status Index, p < .02; Cognitive Difficulties, p < .0001; Symptom Limitations, p = .0001; Center for Epidemiologic Study Depression, p < .0001; General Health Perception, p = .0001). CONCLUSIONS: Postoperative cognitive decline may diminish improvements in QOL. Strategies to reduce cognitive decline may allow patients to achieve the maximum improvement in QOL afforded by CABG, as even short-term cognitive dysfunction has implications for QOL 1 year later.

Aged↗

Treatment delays in the course of electroconvulsive therapy.

Electroconvulsive therapy (ECT) is often delayed because the patient develops cognitive disturbances. The authors reviewed the charts of 45 depressed patients who received ECT and found that 25 patients developed cognitive dysfunctions severe enough to cause a delay in treatment. The development of organic symptoms causing delays in treatment was positively correlated with increased age and the presence of preexisting cognitive dysfunction, and the treatment delays led to longer periods of hospitalization. The authors emphasize the need for early identification of the causes of cognitive dysfunction after ECT and for careful selection of the treatment strategy for each patient to reduce the risk of adverse effects.

Age Factors↗

The FOCIS international survey on psychiatrists' opinions on cognition in schizophrenia.

BACKGROUND: The goal of this project was to develop an interview to evaluate psychiatrists' views on the nature of cognitive dysfunction in schizophrenia, its importance as a potential treatment target, and its relative importance as a treatment target across different phases of schizophrenia. MATERIALS AND METHODS: A survey (available in paper or on-line) consisting of 27 questions, was developed by the Focus on Cognition in Schizophrenia (FOCIS) group, and distributed in a single wave mailing to 63,295 psychiatrists in 21 countries worldwide. RESULTS: The overall response rate was 4.7% (n=2975). The surveyed psychiatrists perceived cognition as a high treatment priority in stabilized schizophrenia patients, but less so for first episode or acute schizophrenia patients. The potential of atypical antipsychotics to improve cognitive dysfunction in schizophrenia was identified by 81% of the respondent psychiatrists. CONCLUSIONS: Cognitive deficits in people with schizophrenia are seen by clinical psychiatrists as relevant to treatment and rehabilitation plans. They were, however, regarded as a higher treatment priority in stabilized chronic rather than in first episode patients. The results suggest clinical psychiatrists need additional education regarding the nature of cognitive dysfunction in schizophrenia and its importance for psychosocial rehabilitation and community re-entry.

Attitude of Health Personnel↗

The cognitive impact of nutritional homocysteinemia in apolipoprotein-E deficient mice.

Homocysteinemia is associated with cognitive dysfunction in the elderly ranging from subtle cognitive decline to dementia. Homocysteine is generated from methionine as a product of biological methylation reactions and is disposed of through reactions that require folate and vitamins B12 and B6. While different disruptions in these reactions can result in homocysteinemia, it is unclear if they will also result in homocysteine-mediated cognitive dysfunction. Young ApoE-deficient mice were fed one of four diets with differing methionine and B-vitamin content for eight weeks, before undergoing psychomotor tests, the Morris Water Maze test of spatial memory and learning, and measurement of home-cage activity. B-vitamin deficiency induced homocysteinemia and selectively impaired Morris Water Maze performance without affecting other behavioral measures. The cognitive deficits occurred in the absence of overt histologic neurodegeneration but in association with moderate impairments of brain methylation potential. Diets that yielded cognitive deficits were different from those that exacerbated aortic pathology. These findings are inconsistent with a single mechanism linking homocysteinemia to neurological dysfunctions mediated by homocysteine vasotoxicity. Instead, they indicate that different "types" of homocysteinemia, or in other words different impairments of nutritional metabolism affecting homocysteine levels, may lead to different end organ dysfunctions and/or diseases.

Animals↗

Mental impairment and utilization of community services: a study of the elderly in a parish of Stockholm.

Before the implementation of the health care reform of 1992 (The Adel Reform), a study of the frequency of mental impairment of people in different residential and care services was conducted in a parish of Stockholm. All residents, 65 years or older, registered with Primary Care Centres, Geriatric Hospitals and other institutions were assessed with respect to cognitive function according to the seven stage "Global Deterioration Scale" (GDS). The age-specific frequencies of mental impairment were similar to prevalences reported in earlier studies. The frequency of cognitive dysfunction of non-institutionalized and institutionalized elderly was 42% and 52%, respectively, and higher for women than for men. There was considerable variation in the prevalence of cognitive dysfunction among subjects in different types of accommodation. For the different stages of mental impairment the average age was about the same. With increasing need and demand for services, and limited resources, these variations in cognitive dysfunction have important implications for structuring appropriate support systems in a population with a rapidly rising proportion of elderly people.

Age Factors↗

Kinetics of tyrosine transport and cognitive functioning in schizophrenia.

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.

Adolescent↗

[Evoked potentials in assessing the sensory, activating and cognitive functions of the normal human brain and in cortical and subcortical types of vascular dementia].

Characteristics of the auditory EP under conditions of stimulus recognition (the P300 technique) and parameters of the visual "nonspecific" EP to light flash were studied in healthy subjects of the wide age range (18-78 years old) and patients with vascular dementia of different severity. It was shown that P300 parameters depended on age in healthy patients and on expression of cognitive dysfunction in demented patients. The changes were more pronounced in dementia of the cortical type. The P300 to nonrelevant stimulus was not age-dependent and slightly changed at cognitive dysfunction. Parameters of the nonspecific visual responses (the latency and duration--the index of homeostatic regulation) and maximal amplitude (reflecting the extent of activation processes) were not age-dependent and changed both in subcortical and cortical dementia types (increase in response latency and duration). In cognitive dysfunctions of subcortical origin homeostatic changes in the form of increase in time of homeostatic regulation and deterioration of stabilization of brain electrical processes were more pronounced.

Adolescent↗

Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey.

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.

Aged↗

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study.

OBJECTIVES: Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS. METHODS: Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated. RESULTS: Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test. CONCLUSIONS: Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.

Aged↗

Cognition in the days following concussion: comparison of symptomatic versus asymptomatic athletes.

BACKGROUND: Concussion is a common neurological injury occurring during contact sport. Current guidelines recommend that no athlete should return to play while symptomatic or displaying cognitive dysfunction. This study compared post-concussion cognitive function in recently concussed athletes who were symptomatic/asymptomatic at the time of assessment with that of non-injured (control) athletes. METHODS: Prospective study of 615 male Australian Rules footballers. Before the season, all participants (while healthy) completed a battery of baseline computerised (CogSport) and paper and pencil cognitive tasks. Sixty one injured athletes (symptomatic = 25 and asymptomatic = 36) were reassessed within 11 days of being concussed; 84 controls were also reassessed. The serial cognitive function of the three groups was compared using analysis of variance. RESULTS: The performance of the symptomatic group declined at the post-concussion assessment on computerised tests of simple, choice, and complex reaction times compared with the asymptomatic and control groups. The magnitude of changes was large according to conventional statistical criteria. On paper and pencil tests, the symptomatic group displayed no change at reassessment, whereas large improvements were seen in the other two groups. CONCLUSION: Injured athletes experiencing symptoms of concussion displayed impaired motor function and attention, although their learning and memory were preserved. These athletes displayed no change in performance on paper and pencil tests in contrast with the improvement observed in asymptomatic and non-injured athletes. Athletes experiencing symptoms of concussion should be withheld from training and competition until both symptoms and cognitive dysfunction have resolved.

Adult↗

Longitudinal consistency of the relationship between depression symptoms and cognitive functioning in multiple sclerosis.

BACKGROUND: Lifetime prevalence rates of cognitive dysfunction and depression in multiple sclerosis (MS) have typically been reported to be approximately 50 percent. However, an inconsistent relationship between these two common features of MS has been reported in the literature. Because neurovegetative depression symptoms overlap with MS symptoms, it may be that literature inconsistencies can partly be explained by the fact that only those depression symptom clusters unambiguously reflective of depression are associated with cognitive dysfunction. OBJECTIVE: To explore the relationship between different depression symptom clusters and a battery of tests measuring cognitive domains commonly impaired in MS and was examined at two time points 3 years apart. METHODS: The Chicago Multiscale Depression Inventory was employed to measure mood, negative evaluative, and neurovegetative symptom clusters in 53 MS patients who were also administered a battery of neuropsychological tests. RESULTS: At time point 1, Mood and Evaluative Chicago Multiscale Depression Inventory scales were significantly associated with tasks of complex speeded attention, planning, and working memory. At time point 2, the Evaluative scale was still significantly associated with these domains, in addition to spatial memory; however, all of the significant correlations with the Mood scale dropped out. CONCLUSION: These results show that negative evaluative depression symptoms are most consistently predictive of cognitive dysfunction in MS. It may be that negative evaluative depression symptoms use up available cognitive capacity, thus compromising performance on cognitive capacity demanding tasks in MS patients.

Cognition Disorders↗

Unraveling the fundamental molecular mechanisms of morphological and cognitive defects in the irradiated brain.

Prenatal radiation exposure may have serious consequences for normal brain development. Results of epidemiological studies clearly pointed towards an increased risk of mental retardation in children of the surviving women of the Hiroshima/Nagasaki atomic bombing when in utero exposure had occurred between weeks 8 and 15 of pregnancy or, at a lower extend between weeks 15 and 25. The high sensitivity of the developing brain, in comparison to the adult brain is related to its higher number of non-differentiated, dividing neural precursor cells. Exposure of the developing brain to ionizing radiation can lead to three main outcomes in the developing brain, depending on the radiation dose and the elapsed period after irradiation. A first event occurs early after irradiation and triggers disturbances in cell proliferation, migration, differentiation, and cell death. A second event involves the generation of morphological abnormalities in the developing brain, if the radiation dose is sufficient. A third event involves cognitive dysfunctions that are a direct consequence from a disturbance in regional brain formation. The latter results from exposure to low doses and is usually only observed in the later period of development. In order to understand the mechanisms of radiation-induced cognitive dysfunctions, it is important to track back the underlying changes in specific molecular pathways. In this review, we present the possible relationships within and between molecular pathways potentially involved in cognitive dysfunctions induced by ionizing radiation in the developing brain.

Animals↗

Formal thought disorder and psychopathology in pediatric primary generalized and complex partial epilepsy.

OBJECTIVE: To examine whether formal thought disorder and psychopathology occurred in children with complex partial seizures (CPS) rather than children with primary generalized epilepsy with absences (PGE) or nonepileptic children. METHOD: Formal thought disorder was coded in 30 children with CPS, 24 children with PGE, and 61 nonepileptic children, and structured interview-based psychiatric diagnoses were obtained for the epileptic subjects. RESULTS: The CPS subjects had significantly more illogical thinking than the PGE and nonepileptic children. The severity of their illogical thinking was related to global cognitive dysfunction and a schizophrenia-like psychosis. Age of onset and seizure control, however, were significantly associated with the severity of illogical thinking in the PGE group. One or more psychiatric diagnoses were found in 63% of the CPS and 54% of the PGE patients, particularly if they had global cognitive deficits. CONCLUSION: Illogical thinking, associated with cognitive dysfunction or schizophrenia-like symptoms, might be a feature of pediatric CPS. Psychopathology might be related to global cognitive dysfunction in pediatric CPS and PGE.

Adolescent↗

Prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement.

OBJECTIVE: To find out the prevalence of vitamin B12 deficiency among demented patients and to look at the effects of cobalamin repletion on cognition in elderly, subjects with low serum cobalamin and evidence of cognitive dysfunction. DESIGN: Time series data collected in a single-blinded trial of parenteral cobalamin therapy. SETTINGS: Nursing home facility and Outpatient geriatric assessment center. PARTICIPANTS: Sixty-two subjects with low serum cobalamin (<300 pg/ml) and evidence of cognitive dysfunction were entered consecutively over a two years period of time. Fifty-six subjects completed the study. INTERVENTIONS: Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of six months. OUTPATIENT MEASURE: The Folstein Minimental Status Examination(MMSE), clock drawing tests, and caregiver interviews were administered both before and at 3 months after full cobalamin replacement therapy. Assessment was repeated thereafter every three months. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms. RESULTS: After a minimum of 12 months of cobalamin therapy, 40 of 56 patients revealed cognitive improvement. There was a prominent correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for <12 months gained an average of six points on the MMSE (paired t test P = 0.0065), whereas patients symptomatic >12 months gained an average of four points (paired t test P = 0.25). Six patients symptomatic for only 3 to six months normalized their MMSE scores, gaining 1,2,3, 6, and 9 points, respectively. CONCLUSION: It seems that there may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin.

Aged↗

Controversial significance of early S100B levels after cardiac surgery.

BACKGROUND: The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for. METHODS: 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion. RESULTS: In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005). CONCLUSIONS: In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

Age Factors↗