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PubMed2001

The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus.

OBJECTIVE: To describe the prevalence of neuropsychiatric (NP) syndromes in a Finnish population of patients with systemic lupus erythematosus (SLE) and to classify them according to the recently developed American College of Rheumatology (ACR) nomenclature and case definitions for NPSLE. METHODS: Cross-sectional, population-based study covering an area with 440,000 people. A total of 58 patients with a definite diagnosis of SLE and aged 16 to 65 years were found in the computerized database of the area hospitals. Of these, 46 (79%) agreed to participate. The diagnosis of various NP syndromes was based on clinical impression (H.A.) following history, examination, review of medical records, and neuropsychologic testing. RESULTS: At least one NP syndrome was identified in 42 patients (91%). The most frequent manifestation was cognitive dysfunction (n = 37; 81%), followed by headache (n = 25; 54%) and mood disorder (n = 20; 43%). When mild NP syndromes (mild cognitive deficit, headache, mild depression, anxiety, electroneuromyography-negative polyneuropathy) were excluded, the prevalence of NPSLE dropped to 46%. CONCLUSIONS: According to the ACR nomenclature, there is a high prevalence of NP manifestations in a population-based sample of patients with SLE. Most NP syndromes were classified as minor; if they were excluded, the 46% prevalence of NPSLE would be slightly less than estimated in previous studies.

Adult↗

PubMed2003

Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging.

Although extensive evidence exists for the reinforcing properties of drugs of abuse such as cocaine, relatively less research has addressed the functional neuroanatomical correlates of the cognitive sequelae of these drugs. We present a functional magnetic resonance imaging study of a GO-NOGO task in which successful performance required prepotent behaviors to be inhibited. Significant cingulate, pre-supplementary motor and insula hypoactivity was observed for both successful NOGOs and errors of commission in chronic cocaine users relative to cocaine-naive controls. This attenuated response, in the presence of comparable activation levels in other task-related cortical areas, suggests cortical and psychological specificity in the locus of drug abuse-related cognitive dysfunction. The results suggest that addiction may be accompanied by a disruption of brain structures critical for the higher-order, cognitive control of behavior.

Adult↗

PubMed2004

Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness.

BACKGROUND: Truly effective treatments for schizophrenia require much more than clinical efficacy. Symptom improvement is all that is required to demonstrate clinical efficacy. However, for a treatment to be effective in a wide-ranging manner, improvement in various life domains, such as social functioning, independent living, and employment, should also be found. Thus, a much wider range of improvements, not widely produced by previous treatments, is required to take treatment for schizophrenia to a new level of effectiveness. CONSENSUS PROCESS: A teleconference consensus meeting was held with the bylined authors on December 10, 2002, to explore the factors that hinder the most effective treatments for schizophrenia. We argue that a possible unifying factor underlying these apparently disparate domains of effective treatment is cognitive functioning, which is impaired in people with schizophrenia. Treatment of cognitive dysfunction may have a central role in increasing the breadth of effective treatment for schizophrenia. CONCLUSIONS: Novel antipsychotics and specific cognitive-enhancing medications have preliminarily been shown to have cognitive benefits that might lead to broader effectiveness of treatments, eventually reflected in improvements in the daily lives of patients. These treatments may have their greatest impact when combined with focused psychological interventions. While the research to date does not provide a large number of successes, this area will be one of considerable research interest for the next decade, with developments likely to be very important to clinicians treating patients with schizophrenia.

Antipsychotic Agents↗

PubMed2006

Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of circulating anti-NR2 antibodies and their association with neuropsychiatric systemic lupus erythematosus (NP-SLE), particularly cognitive function, in women with SLE. METHODS: Cognitive function was assessed in 65 consecutive women with SLE from a single referral center using standardized neuropsychological tests. These were selected subtests of the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test, which provided information on 8 areas of cognitive function. After a mean followup of 64 (range 52-71) months, cognitive assessments were repeated. Global and domain-specific cognitive impairment was examined using predetermined decision rules, and the change in individual tests of cognitive performance over time was also examined. Overt NP-SLE was identified by clinical assessment and classified using the American College of Rheumatology nomenclature. Circulating IgG anti-NR2 and anti-dsDNA antibodies were determined by ELISA on up to 4 occasions over the study period. A positive result was defined as at least 3 standard deviations above the mean of healthy controls. RESULTS: At enrollment, 15/65 (23%) patients had cognitive impairment. This fell to 7/54 (13%) at followup. In addition 15/65 (23%) patients had a history of clinically overt NP-SLE. Twenty-three of 65 (35%) patients had anti-NR2 antibodies and 48/65 (74%) had anti-dsDNA antibodies. Anti-NR2 antibodies were present in 18/48 (38%) patients with anti-DNA antibodies, and 18/23 patients (78%) with anti-NR2 antibodies also had anti-dsDNA antibodies. There was no association between global cognitive impairment, domain-specific cognitive impairment, or a history of clinically overt NP-SLE and either the presence or amount of anti-NR2 or anti-dsDNA antibodies (p > 0.05). When change in cognitive performance or the occurrence of new NP-SLE events over the 5-year followup period was examined, there was no significant association with persistent elevation of either antibody (p > 0.05). Similarly there was no association between a rise in autoantibodies over time and the development of overt NP events or cognitive decline (p > 0.05). CONCLUSION: These results indicate that anti-NR2 antibodies occur in 35% of women with SLE and are infrequent in the absence of detectable anti-dsDNA antibodies. Their presence in the circulation is not associated with cognitive dysfunction at a single timepoint, and an increase in or persistently elevated antibody levels are not associated with a change in cognitive performance over time. There was no association with clinically overt NP-SLE. However, as our study did not examine cerebrospinal fluid samples, these results do not exclude a potential pathogenic role in selected patients for this group of autoantibodies should they penetrate the blood-brain barrier and thereby gain direct access to neuronal tissues.

Adult↗

PubMed1996

The relationship between complaint-related cognitions in referred patients with irritable bowel syndrome and subsequent health care seeking behaviour in primary care.

BACKGROUND: It is generally accepted that it is important to explore patients' beliefs and fears about the meaning of their symptoms during medical consultations. OBJECTIVE: To discover how referral behaviour of GPs and attention to dysfunctional cognitions of medical specialists affect the subsequent health care seeking behaviour of patients with irritable bowel syndrome. METHOD: Questionnaires were distributed to GPs and to doctors and patients at an outpatient clinic in the University Hospital of Nijmegen. RESULTS: The results of the present study indicate that doctors' attention to the complaint-related cognitions of IBS-patients is also related to a reduced use of medical health services in primary care. On the other hand, when referred IBS-patients continue to attribute their complaints to a somatic abnormality even after such an abnormality has been ruled out through extensive physical examinations, the subsequent use of medical health services in primary care is likely to increase. Moreover, GPs' referral behaviour appears to strengthen these dysfunctional somatic attributions in IBS-patients. CONCLUSION: These unfavorable consequences might be avoided by handling cognitions and anxiety more specifically during medical consultations in primary as well as secondary care.

Adult↗

PubMed2001

Decrease in jugular venous oxygen saturation during normothermic cardiopulmonary bypass predicts short-term postoperative neurologic dysfunction in elderly patients.

OBJECTIVES: We sought to examine whether the decrease in jugular venous oxygen saturation (SjvO(2)) during cardiopulmonary bypass (CPB) can be used to predict short-term and long-term postoperative cognitive disorders in elderly patients. BACKGROUND: It has been reported that elderly patients might be more susceptible to hypoperfusion during CPB. METHODS: One hundred eighty-five patients scheduled for elective coronary artery bypass graft surgery were studied. Group 1 (n = 56) was young (<50 years old), group 2 (n = 67) was middle-aged (50 to 69 years old) and group 3 (n = 62) was elderly (>70 years old). After induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor SjvO(2) continuously. Hemodynamic variables and arterial and jugular venous blood gases were measured at seven time points. RESULTS: The cerebral desaturation time (duration when SjvO(2) was <50%) and the ratio of the cerebral desaturation time to the total CPB time in group 3 were significantly different from those in groups 1 and 2 (group 1: 20 +/- 6 min and 16 +/- 5%; group 2: 19 +/- 7 min and 14 +/- 6%; group 3: 34 +/- 9 min and 24 +/- 7%, respectively; p < 0.05). Also, age (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0 to 1.8, p = 0.02) and desaturation time (OR 1.3, 95% CI 1.0 to 1.4, p = 0.03) were perioperative factors in relation to short-term cognitive impairment. However, age and desaturation time were not perioperative factors in relation to long-term cognitive impairment. CONCLUSIONS: Reduced SjvO(2) was associated with short-term cognitive dysfunction in elderly patients.

Age Factors↗

PubMed1995

Tardive dyskinesia in schizophrenia. Relationship to minor physical anomalies, frontal lobe dysfunction and cerebral structure on magnetic resonance imaging.

BACKGROUND: It was hypothesised that schizophrenic patients with tardive dyskinesia show an excess of neurodevelopmental disturbance, particularly minor physical anomalies, in association with cognitive dysfunction and abnormalities of cerebral structure. METHOD: Forty-seven out-patients with a DSM-III diagnosis of schizophrenia were examined for tardive dyskinesia using the Abnormal Involuntary Movement Scale; they were examined also for minor physical anomalies and neuropsychological test performance. Cortical atrophy, signal hyperintensities and lateral ventricular volume were determined on magnetic resonance imaging. RESULTS: Patients with and without tardive dyskinesia could not be distinguished by age, gender distribution or a number of clinical measures; however, patients with tardive dyskinesia sorted fewer categories on the Wisconsin Card Sorting Test (P = 0.04). Cerebral structure in patients with and without tardive dyskinesia could not be distinguished on magnetic resonance imaging but those with dyskinesia, all of whom showed involvement of the orofacial region, showed more evident minor physical anomalies of the head relative to those of the periphery (P = 0.02). CONCLUSIONS: Tardive orofacial dyskinesia in schizophrenia appears to be associated particularly with poorer frontal lobe function, while predominance of craniofacial dysmorphogenesis may constitute a vulnerability factor that is related to the early origins of the disease process.

Adult↗

PubMed1989

Neuropsychological and neurological function of human immunodeficiency virus seropositive asymptomatic individuals.

Although individuals with acquired immunodeficiency syndrome (AIDS) are often impaired on a variety of neuropsychological tasks, questions remain as to when neuropsychological decline can be reliably detected during the course of human immunodeficiency virus (HIV) infection. Detailed neuropsychological testing was accomplished on a cohort of 83 immunologically and neurologically intact asymptomatic HIV-infected individuals drawn from a larger pool of 649 US Air Force personnel with HIV antibodies. These asymptomatic subjects were compared with a group of HIV-negative subjects, and no significant differences in neuropsychological functioning were found. No significant neuropsychological differences were found as a function of cerebrospinal fluid abnormalities in these asymptomatic subjects. When data from 13 subjects with immune compromise were included in the analyses, those with abnormal cerebrospinal fluid values performed significantly poorer on a task of verbal memory, suggesting that cognitive dysfunction is antedated by immunological decline. Methodological problems that inhibit specification of the incidence, prevalence, and natural history of HIV-related cognitive impairment are discussed, as are data suggesting that previously published high estimates of the frequency of HIV-related dementia may not be representative of all HIV-infected populations.

Central Nervous System↗

PubMed1998

Quality of life perception in patients with intractable epilepsy or pseudoseizures.

OBJECTIVES: To contrast and compare self-reported quality of life in patients with intractable epilepsy and pseudoseizures and to examine the relationship between self-reports and objective measures of cognitive functioning in both of these groups. DESIGN: Case series using profile analysis and analysis of covariance. SETTING: University epilepsy surgery program. PARTICIPANTS: Forty-three patients with intractable complex partial seizures of unilateral temporal lobe origin and 25 patients with pseudoseizures. MEASURES: Quality of Life in Epilepsy Inventory-89; neuropsychological tests assessing verbal memory, nonverbal memory, naming, and attention; and the Depression Scale (2) of the MMPI-2 (Minnesota Multiphasic Personality Inventory). RESULTS: Patients with pseudoseizures described themselves as more limited in the physical health domain than patients with complex partial seizures. Self-perceptions of cognitive functioning were similar between groups, despite the superior performance of patients with pseudoseizures on objective measures. Self-perception of cognitive dysfunction was related to mood disorder in the pseudoseizure group only, and there were no relationships between subjective and objective measurements of cognitive status within this group independent of mood disorder. For the complex partial seizures group, relationships between subjective and objective measures of cognitive function were dependent on the side of seizure onset. CONCLUSIONS: Results are consistent with hypotheses that suggest that patients with pseudoseizures focus on physical rather than psychological explanations for stress, and that this focus is related, at least in a subgroup of patients, to mood disorder. Results also provide support for the validity of the Quality of Life in Epilepsy Inventory-89 in populations with intractable seizure disorder, although there is evidence for a possible floor effect on some of the subscales.

Adolescent↗

PubMed2003

Generalized cognitive impairment in male adolescents with schizotypal personality disorder.

Schizotypal Personality Disorder (SPD) shares common genetic and biological substrates with schizophrenia, and patients with SPD have been reported to suffer both from specific cognitive impairments, and from a generalized cognitive dysfunction, similar to those found in schizophrenia. The aim of this cross-sectional, population-based study was to assess general cognitive functioning in adolescents with SPD. The Israeli Draft Board systematically assesses cognitive functioning and administers psychiatric screening in all 16-17-year-old males in the population. Of 341,511 males assessed, the cognitive test scores of adolescents with SPD (N = 326) were retrieved, and compared to the scores of adolescents diagnosed as suffering from schizophrenia (N = 901), and adolescents with no neurological or psychiatric diagnosis (controls, N = 293,820). Male adolescents with SPD or with schizophrenia scored lower on all measures compared to healthy individuals (effect sizes ranging from 0.6-0.88, all P < 0.001). The SPD patients scored significantly higher than the schizophrenia patients on the sub-tests of similarities and Ravens Progressive Matrices, tests that reflect abstract reasoning. On the sub-tests of arithmetic and instruction comprehension, tests that rely on concentration, SPD and schizophrenia patients' scores did not differ significantly from each other. These results might be interpreted to imply that a generalized cognitive impairment, in the presence of schizotypal personality traits and in the absence of psychosis, might be conceptualized as being the core of the schizotaxia syndrome. The greater impairment in abstract reasoning in the schizophrenia patients might be correlated with the psychotic symptoms that differentiate schizophrenia from SPD.

Adolescent↗

PubMed2004

Magnetic resonance spectroscopy in cognitive research.

The neurophysiological basis of cognition is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event-related potentials, brain size and cerebral blood flow. Magnetic resonance spectroscopy (MRS) is an in vivo method used to detect neurochemicals within the brain that are relevant to certain brain processes. The most widely used methods are 1H-MRS and 31P-MRS, which detect compounds that contain hydrogen and phosphorus, respectively. Recent studies have shown that the absolute concentrations or ratios of these neurochemicals, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in normal subjects. Many studies in adults and children have shown a relationship between neurometabolite values and cognitive status or extent of cognitive dysfunction in various neurological and neuropsychiatric disorders. We review these studies and conclude that MRS has potential applications for the study of cognitive processes in health and disease and may be used clinically for differential diagnosis, the early detection of pathology and the examination of longitudinal change.

Animals↗

PubMed2006

Cerebrovascular risk factors do not contribute to genetic variance of cognitive function: the ERF study.

Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.

Adult↗

PubMed2005

Limbic over-activity in depression during preserved performance on the n-back task.

The profile of cognitive dysfunction observed in patients with major depressive disorder (MDD) may be partially attributed to a deficit in the central executive component of working memory (WM). This could be the consequence of a functional deficit in regions of cortex that are associated with WM function in healthy adults. In order to investigate this assertion, ten patients with a diagnosis of MDD and ten matched healthy controls undertook a parametric WM task (i.e. the n-back task) during the acquisition of blood oxygen level dependent echo planar magnetic resonance images (BOLD EPI fMRI). There was no significant difference in the behavioral performance of depressed patients and controls. This was true for both accuracy and reaction time on the n-back task. Random effects analysis of the functional imaging data (using SPM99) revealed a significant difference in load-dependent activation in the medial orbitofrontal cortex/rostral anterior cingulate between patients and controls (cluster size (K(E))/volume = 128/1024 mm3, P(corrected) = 0.025). While both participant groups exhibited a significant decrease in activation in this region with increased task difficulty, the magnitude of this decrease was smaller in patients with MDD than in controls. Therefore, this study implies that the performance of WM tasks is associated with a dysfunctional activation of the medial orbitofrontal and rostral anterior cingulate cortex in MDD. The study thus offers a rationale for explaining depressive cognitive impairment by the abnormal fronto-limbic activation found in clinical depression.

Adult↗

PubMed2003

[Lacunar infarcts].

Lacunar infarcts, small deep infarcts resulting from occlusion of a penetrating artery, account for about a quarter of all ischemic strokes. The view of lacunar infarcts as a benign and rather innocent vascular lesion has been modified during the last years. Although the prognosis is more favourable than other subtypes during the first years, probably due to the small lesion size, in a longer perspective there is an excess risk of death, continual occurrence of recurrent stroke, and development of cognitive dysfunction. The risk of recurrent stroke is similar to most other types of stroke, and patients are at increased risk to develop cognitive decline and dementia. Increasing age, vascular risk factors, and high nocturnal blood pressure have significant prognostic implications for almost all outcomes. Lacunar infarcts and ischemic white-matter disease, the two main types of cerebral small-vessel disease, frequently co-exist and have synergistic effects on prognosis and risk of cognitive decline. Antiplatelet therapy and risk factor modification are the cornerstones in secondary prevention after a lacunar infarct.

Adult↗

PubMed1978

Adaptational factors in memory function in the aged.

Memory function in the aged is described as due to the interaction of a number of variables in addition to physiology, including affective state and environmental conditions. Depression can cause a series of behavioral patterns ranging from exaggeration of memory complaint, to simulation of organic dysfunction, to "pseudodementia" in which there is production of an actual organic mental syndrome. Stress and noxious environmental conditions also contribute to cognitive dysfunction. Custodial care is singled out as especially harmful, producing a form of "excess disability" termed "unorientation" in which apparently impaired memory results from an apathetic, withdrawn reaction to the environment. All these adaptational patterns are subject to prevention, modification, and in some cases, reversal.

Adaptation, Psychological↗

PubMed1998

Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to chromosome 2p.

A family initially considered to have 'pure' autosomal dominant hereditary spastic paraparesis (HSP), was found on neuropsychological testing to have evidence of late onset cognitive impairment. This family showed genetic linkage to the SPG4 locus on chromosome 2p previously reported for pure HSP. Of 56 living members, 44 were examined, 30 of whom were > 30 years of age and 12 members were found to be affected with HSP including four asymptomatic cases. One other family member (III-5), aged 62 years, died prior to this study of a 4-year dementing illness. Neuropsychological assessment of 11 affected members and 11 matched, unaffected, family controls showed no significant differences between the two groups. However, the neuropsychological test profile in four of 11 affected members tested (mean age 47.2 years) and one of 11 family controls (mean age 41.5 years) showed global cognitive impairment. The pattern of cognitive dysfunction was the same for all five family members identified and was similar to that found in subcortical dementia. The presence of cognitive impairment appeared to be related to age and not the severity of the paraplegia. Both the severity of the paraplegia and the age of onset (21-60 years) varied considerably in this family.

Adult↗

PubMed2003

Targeted psychosocial interventions for bipolar disorder.

Pharmacotherapy is the foundation of treatment for bipolar disorder, but research suggests that adjunctive psychosocial interventions that are manualized, reproducible, time-limited, empirically supported, and strategically target a number of critical domains, can efficiently provide additional benefits. Psychoeducation as an adjunct of pharmacotherapy may be beneficial, but questions remain about the utility of this treatment for patients who are already compliant with medication treatment. Family educational interventions have demonstrated encouraging results in relapse prevention, but follow-up data are limited and application to patients who have limited social networks may be problematic. Reports on interpersonal and social rhythm therapy in patients with bipolar disorder are scarce, and what is available shows no differential effect on time to remission or relapse, but a significant impact on subsyndromal symptoms. Follow-up data suggest that patients receiving cognitive behavior therapy have significantly fewer bipolar episodes, shorter episodes, fewer hospitalizations, and less subsyndromal mood symptoms. It is unclear, however, if cognitive behavior therapy is superior to other active psychosocial treatments and whether its mechanism in patients with bipolar disorder is through changing dysfunctional cognitions or simply enhancing early symptom detection. Psychotherapies should be considered early in the course of illness to improve medication compliance and to help patients identify prodromes of relapse in order to take steps for prevention. In addition, some strategies may have a beneficial effect on residual symptoms, particularly symptoms of depression, and thus help move patients toward a more comprehensive functional recovery.

Bipolar Disorder↗

PubMed2006

The thalamus and behavior: effects of anatomically distinct strokes.

Data on behavioral changes after thalamic lesion are sparse and largely based on isolated reports of patients with thalamic strokes. However, recent findings suggest that behavioral patterns can be delineated on the basis of the four main arterial thalamic territories. The anterior pattern consists mainly of perseverations and superimposition of unrelated information, apathy, and amnesia. After paramedian infarct, the most frequent features are disinhibition syndromes, with personality changes, loss of self-activation, amnesia, and, in the case of extensive lesions, thalamic "dementia"; this pattern may often be difficult to distinguish from primary psychiatric disorders, especially when neurologic dysfunction is lacking. After inferolateral lesion, executive dysfunction may develop but is often overlooked, although it may occasionally lead to severe long-term disability. After posterior lesion, whereas cognitive dysfunction with neglect and aphasia are well known, no specific behavioral syndrome has been reported. In the future, perfusion CT, functional MRI, and tractography using diffusion imaging in stroke patients may provide a better understanding of the role of the corticothalamic relationship in behavioral changes associated with thalamic stroke.

Humans↗