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PubMed2006

Suppressive effect of clozapine but not haloperidol on the increases of neuropeptide-degrading enzymes and glial cells in MK-801-treated rat brain regions.

MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces neurotoxicity in adult rodent brain, and causes schizophrenia-like psychosis and cognitive dysfunction. Since neuropeptides and neuropeptide-degrading enzymes play important roles in cognitive function, we examined whether or not MK-801-induced schizophrenia-like psychosis is co-related with the changes of these enzymes in rat brain regions. In the present study, we investigated the effect of systemic treatment with MK-801 (0.5mg/kg) on neuropeptide-degrading enzymes, prolyl oligopeptidase (POP) and thimet oligopeptidase (EP 24.15), and glial marker proteins GFAP and CD11b in rat brain regions. The levels of POP and EP 24.15 activities increased significantly three days after treatment with MK-801 in the posterior cingulate/retrosplenial cortices (PC/RSC). Since atypical neuroleptic clozapine but not typical neuroleptic haloperidol prevents the MK-801-induced schizophrenia-like symptoms, we further examined the pretreated effects of the neuroleptics. Clozapine, but not haloperidol, significantly attenuated MK-801-induced changes in the levels of the neuropeptide-degrading enzymes. Immunohistochemical studies on GFAP and CD11b showed the increase in the PC/RSC of MK-801-treated rat brain and the pretreatment with clozapine suppressed these changes. Double immunostain experiments of EP 24.15 and GFAP antibodies demonstrated some co-localization of the neuropeptidase with astrocytes. The present findings suggest that change of neuropeptidases in the brain is in part correlated with changes of glial cells, and may play an important role in the control of schizophrenia-like psychotic disorders.

Animals↗

PubMed2005

Functional brain imaging of symptoms and cognition in schizophrenia.

The advent of functional magnetic resonance imaging and positron emission tomography has provided novel insights into the neural correlates of cognitive function and psychopathological symptoms. In patients with mental disorders, cognitive and emotional processes are disrupted. In this chapter, we review the basic methodological and conceptual principles for neuroimaging studies in these patients. By taking schizophrenia as an example, we outline the cerebral processes involved in the symptoms of this disorder, such as auditory hallucinations and formal thought disorder. We also characterize the neural networks involved in their emotional and cognitive dysfunction.

Brain↗

PubMed2004

Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review.

Adult subjects with classical phenylketonuria (PKU) who were diagnosed and treated neonatally participated in this long-term follow-up study. Twenty-four subjects received neuropsychological (NP) assessment and a subset received magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to identify: (1) pattern of cognitive dysfunction; (2) effect of high blood phenylalanine (Phe) level at time of cognitive testing; and (3) treatment variables that may be associated with cognitive difficulties in adulthood. All subjects had average IQ except one subject in the borderline range. Diet was initiated by the 15th day of life. All subjects except one were on diet until age 6 years (mean years of treatment = 15). Blood Phe levels at cognitive testing ranged from 157 to 1713 micromol/L (mean = 1038); 11 subjects had levels < 1000 micromol/L and 13 subjects had levels >1000 micromol/L. Results suggest that adults with early-treated PKU demonstrate specific cognitive deficits, a number of which are associated with the frontal and temporal area of the brain. Deficits were noted in several domains including executive functioning, attention, verbal memory, expressive naming and verbal fluency. Self-report measures of depression and anxiety were generally in the normal/mild range. The group with a Phe level > 1000 micromol/L scored lower than the group with Phe level < 1000 micromol/L on measures of focused attention, verbal fluency, reaction time, verbal recognition memory, visual memory and naming. Tests of cognitive functioning were often correlated with measures of treatment during childhood rather than with Phe level at the time of cognitive testing. Subjects with abnormal MRI scored significantly lower on two cognitive tests (Trails A and CVLT Recognition Memory). We found no significant correlation between current brain Phe level obtained through MRS (n = 10) and neuropsychological functioning. Future longitudinal investigation with a larger sample size will assist in clarifying the aetiology of neuropsychological deficits and association with treatment history.

Adult↗

PubMed1994

Social-cognitive processes of severely violent, moderately aggressive, and nonaggressive boys.

This study examined social-cognitive processes of aggressive and nonaggressive boys at preadolescent and early adolescent age levels. The social-cognitive variables included processing of cues, attributions, social problem solving, affect labeling, outcome expectations, and perceived competence and self-worth. Results indicated that a wide range of social-cognitive processes is distorted and deficient for violent and moderately aggressive children, and that different types of social cognition contribute unique variance in discriminating among groups. Severely violent boys at both age levels had difficulties with cue recall, attributions, social problem solving, general self-worth, and a pattern of endorsing unusually positive affects that they may experience in different settings. Moderately aggressive boys shared some of the social-cognitive difficulties demonstrated by severely violent boys, but they also displayed indications that their aggression may be more planfully aimed to achieve expected outcomes. When the moderately aggressive and the violent boys differed from the nonaggressive boys on attributional biases and low perceived self-worth, a continuum existed with violent boys displaying more extreme social-cognitive dysfunctions than the moderately aggressive boys. These findings carry implications for cognitive-behavioral intervention with severely violent and moderately aggressive youths.

Adolescent↗

PubMed2005

Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats.

Clinical symptoms in multiple sclerosis include cognitive dysfunction. Difficulties in learning and remembering new information represent the most common cognitive deficit and are associated with a general and progressive brain pathology. Possible pathogenetic mechanisms for neuronal damage such as neuroprotective strategies are under active investigation also in experimental allergic encephalomyelitis, the most widely used experimental model for multiple sclerosis. In this paper we demonstrate that a selective deficit in learning and memory performance, as investigated by the Morris water maze test, is a consistent feature in rat encephalomyelitis, which correlates with a decline in choline acetyltransferase activity and nerve growth factor mRNA level in cerebral cortex, hippocampus, and basal forebrain. Treatment aimed to restore acetylcholine content through chronic administration of selective acetylcholinesterase inhibitors (rivastigmine and donepezil) restores cognitive performance, choline acetyltransferase activity, and nerve growth factor mRNA expression.

Animals↗

PubMed2001

Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey.

BACKGROUND: High circulating total homocysteine (tHcy) concentrations are associated with stroke, which is a major cause of cognitive dysfunction. Blood homocysteine concentrations are inversely correlated with performance on some cognitive-function tests and a relation was recently shown between hyperhomocysteinemia and Alzheimer disease. OBJECTIVE: The objective was to evaluate the relation between serum tHcy concentrations and performance on short delayed-recall tests of elderly men and women participating in the third National Health and Nutrition Examination Survey, phase 2 (1991--1994). DESIGN: Subjects were aged > or =60 y. Subjects reported no previous stroke, completed > or =8 y of education, and took a test of delayed recall of story ideas (n = 1200) or words (n = 1270). RESULTS: After adjustment for sex, age, race-ethnicity, income, years of education, and serum creatinine concentration, subjects in the upper half of the folate distribution recalled, on average, >4 of 6 story ideas; subjects with lower folate status recalled significantly fewer ideas (P < 0.001). Of the subjects with low folate status, story recall was significantly poorer in those with serum tHcy concentrations above the 80th percentile of the distribution (13.7 micromol/L) than in those with lower tHcy concentrations (P < 0.03). The odds ratio relating hyperhomocysteinemia to recall of > or =1 of 3 previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5 demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for serum folate concentration. CONCLUSION: Hyperhomocysteinemia is related to poor recall and this association was partially independent of folate status.

Age Factors↗

PubMed1984

Substantive and methodological issues in a rating of cognitive and psychological function in multiple sclerosis.

There is a need for a practical, reliable, and valid rating scale for cognitive function in Multiple Sclerosis due to the high frequency of cognitive dysfunction and its consequences for patients and family. The process of rating cognitive function is examined from the point of view of the observer, the observed, and the examination and rating scales. It is concluded that observers can be trained to reduce bias and increase reliability. The patient may be a source of information through diaries, check lists, and interviews. Rating items must be based on the major cognitive deficit factors in multiple sclerosis. Standardized examination must be the basis for ratings. Rating items must be clear and closely tied to observable behaviour. A series of steps for a project to develop an acceptable international cognitive rating scale is proposed.

Cognition Disorders↗

PubMed1993

Auditory event-related potentials in patients with systemic lupus erythematosus.

We studied auditory event-related potentials (ERPs) in 17 patients with systemic lupus erythematosus (SLE). Latencies of N100 and P200 components were normal in all patients, whereas the latencies of target P300 and nontarget P300 components were significantly prolonged in SLE patients with and without cognitive dysfunction. The P300 component of ERPs can be applied to evaluate the cognitive aspects of central nervous system manifestations in SLE patients.

Adult↗

PubMed2002

Cognitive and behavioral features discriminate between Alzheimer's and Parkinson's disease.

OBJECTIVE: To compare the cognitive and behavioral profiles of Alzheimer's disease (AD) and cognitively impaired patients with Parkinson's disease (PD) and to determine the individual measures that best discriminate the two patient groups. BACKGROUND: Neuropsychologic studies of patients with AD and PD have generated debate over the distinction between "cortical" and "subcortical" dementias, with some studies showing significant differences and others showing little difference in the cognitive profiles of these groups. Studies evaluating behavioral differences between the patient groups have been somewhat more successful in adequately discriminating these syndromes. To address this issue, we examined cognitive and behavioral profiles of patients with AD and cognitively impaired patients with PD on two frequently used assessment instruments. METHOD: Patients were diagnosed according to published and accepted criteria for AD and PD. Eighteen patients with AD and 18 patients with PD, matched on age and education, were administered the Mattis Dementia Rating Scale and Frontal Systems Behavior Scale (formally Frontal Lobe Personality Scale). RESULTS: The two groups did not differ on overall Dementia Rating Scale score or total Frontal Systems Behavior Scale score. However, examination of subscale scores revealed that the patients with AD performed significantly worse than the patients with PD on the Memory subscale of the Dementia Rating Scale, and patients with PD were rated as being more apathetic than the patients with AD on the Frontal Systems Behavior Scale. When these two variables were entered into a discriminant function analysis, an overall classification accuracy of 86% was demonstrated, with 89% of the AD group and 83% of the PD group correctly classified. CONCLUSIONS: These findings suggest that even though global cognitive dysfunction and behavioral disturbance may appear similar in patients with AD and cognitively impaired patients with PD, specific measures of these functions that are sensitive to the underlying neuropathology of each disease do differ significantly.

Aged↗

PubMed2003

Single suture synostosis and intracranial hypertension.

It is difficult to determine the incidence and importance of intracranial hypertension in children with single suture synostosis. A review of the literature suggested that some number of affected children have high intracranial pressure. The incidence of cognitive disability also appears to be high in this population. Currently, it cannot be proven that the intracranial hypertension seen in these children causes the cognitive dysfunction or that, for the group as a whole, surgical intervention alters cognitive outcome.

Child↗

PubMedDate not supplied

Cognitive-behavioral-expressive interventions with aggressive and resistant youths.

Research into the nature of aggressive behavior in youths has demonstrated that these youths are often the victims of abuse, exhibit aggressive behavior in early childhood, and remain aggressive into young adulthood. The treatment approach described in this article is a modification of Monahan's [1981] model of the prediction of violent behavior and the anger-management approach of Novaco [1985], and integrates the developmental models of Piaget [1963] and Erikson [1959]. The program is a combination of cognitive, behavioral, and expressive therapies and is targeted to the reduction of dysfunctional cognitive, affective, behavioral, and problem-solving patterns of aggressive youths. As referrals of such aggressive clients are often involuntary, interventions with unwilling and resistant clients are also presented.

Adolescent↗

PubMed2005

[Vascular dementia: the dubious disease].

Vascular dementia is not a disease or even a clearly defined disorder. It is a construct, which brings together very heterogeneous disturbances at the clinical, pathological and etiological levels. Due to the absence of neuropathologic diagnostic criteria, the frequency of associated degenerative pathology (mainly of Alzheimer type), and the heterogeneity of the construct, its clinical diagnosis remains questionable using various diagnostic criteria. The concept of vascular cognitive impairment (VCI) has been proposed as a substitute for vascular dementia to provide some clarification about the relationship between ischemic brain lesions and cognitive dysfunction. Its main interest is to allow diagnosis and treatment of minor cognitive deficits associated with ischemic brain lesions before the occurrence of dementia. Clinical and neuropsychological manifestations of VCI are of fronto-subcortical type, quite distinct from those of Alzheimer's disease. From a practical point of view, the main point is to find out and to treat the vascular risk factors which cause cognitive deficits by themselves or increase those associated with Alzheimer's disease.

Arterial Occlusive Diseases↗

PubMed1980

Diagnostic criteria for primary neuronal degeneration of the Alzheimer's type.

The diagnosis of patients presenting with memory or attentional deficits characteristic of dementia is a growing problem. Dementia may be symptomatic of a range of reversible medical and psychiatric conditions which appear to be indistinguishable from primary neuronal degeneration of the Alzheimer's type. While Alzheimer's disease is a neuropathological diagnosis, the importance of establishing a presumptive diagnosis which can be employed for investigational as well as clinical use is underscored. This paper proposes a diagnostic schema which reflects the current understanding of this disorder. There must be evidence of gradual progressive mental deterioration in attention, learning, memory, cognitive style, motivation, and higher order thinking. A comprehensive medical and psychiatric evaluation is obligatory to eliminate reversible physical illness, psychiatric disorder, or cerebrovascular condition as underlying causes of cognitive dysfunction.

Aged↗

PubMed2001

Cognition in schizophrenia.

Cognitive dysfunction has been described as a hallmark feature of schizophrenia since the first descriptions of the illness. Kraepelin described a number of features of the disorder that he thought reflected impairments in cognition and attention. He also speculated that cognitive impairments were mediated by neurobiologic dysfunction, specifically impairments in the functions of the frontal lobe. Since Kraepelin's time, there have been many changes in the general conceptions of schizophrenia, including ideas regarding the status and importance of cognitive impairment in the illness. Due to increased sophistication of neuropsychologic assessment and neuroimaging techniques, cognitive impairment has again has risen to the forefront of importance in terms of theories regarding the etiology and treatment of schizophrenia.

Attention↗

PubMed1991

Implications of self-reported cognitive and motor dysfunction in HIV-positive patients.

OBJECTIVE: The authors examined HIV-positive subjects to determine the relationship of patient complaints of cognitive and motor dysfunction to psychiatric status and performance on established cognitive and motor function tests. METHOD: HIV-positive volunteers (N = 77) were evaluated at entry into a longitudinal neurological study. Forty were asymptomatic, 29 had AIDS-related complex, and eight had AIDS. The subjects were not selected for the presence or absence of cognitive or motor complaints. Complaints of cognitive and motor dysfunction were assessed with items from the AIDS Clinical Trials Group Macro Neurologic Exam. Current depression and anxiety were assessed with the Profile of Mood States. Psychiatric status was assessed with the NIMH Diagnostic Interview Schedule, a structured interview that provides DSM-III psychiatric diagnoses. Actual cognitive and motor performance was measured with standard neuropsychological tests known to be sensitive to the effects of HIV. RESULTS: Cognitive complaints were found in 38 (49%) of the subjects. These complaints were associated with psychiatric symptoms but not with cognitive performance. Motor complaints, found in 12 (16%) of the subjects, were associated with poorer motor performance but not with psychiatric symptoms. The overall frequency of psychiatric diagnosis was high. CONCLUSIONS: Self-reports of cognitive and motor dysfunction were common in this unselected group and are of concern to health care providers. Potentially treatable psychiatric conditions were also common, particularly in subjects with cognitive complaints, and appropriate treatment referrals are indicated. Patients who report motor dysfunction should be neurologically evaluated for treatable causes.

AIDS Dementia Complex↗

PubMedDate not supplied

Enhanced cognitive-behavioral therapy for vocational rehabilitation in schizophrenia: Effects on hope and work.

To address the effects of dysfunctional cognitions on vocational outcome of people with schizophrenia spectrum disorders, we developed the Indianapolis Vocational Intervention Program (IVIP), a cognitive-behavioral program of group and individual interventions. Fifty participants with schizophrenia or schizoaffective disorder were offered 6-month work placements and randomized to receive IVIP (n = 25) or standard support services (n = 25). Hours worked were measured weekly, and work performance was assessed biweekly with the use of the Work Behavior Inventory. Hope and self-esteem were assessed at baseline and at 5 months with the Beck Hopelessness Scale and the Rosenberg Self-Esteem Schedule. Analysis of variance (ANOVA) revealed that the IVIP group worked significantly more weeks and had better average work performance than the standard support group. Repeated measures ANOVA of baseline and follow-up scores indicated that the IVIP group sustained baseline levels of hope and self-esteem through follow-up, while the standard support group experienced declines. Results provide initial evidence of the effectiveness of the IVIP.

Adult↗

PubMed2000

Assessment of the damage of the cerebral hemispheres in MS using neuroimaging techniques.

The pattern of mental dysfunction in multiple sclerosis (MS) is characteristic of the so-called subcortical dementia. Cognitive dysfunction results predominantly by the disruption of communication among cortical and subcortical areas, as a consequence of the white matter damage. As expected, studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to the lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by the invisible damage in the normal-appearing white matter (NAWM). Recent studies using non-conventional MRI techniques with a higher specificity for the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM, support this interpretation. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

Brain Diseases↗

PubMed2005

Correlates of cognitive impairment among patients with heart failure: results of a multicenter survey.

PURPOSE: Cognitive impairment is an exceedingly prevalent condition among patients with heart failure, independently associated with disability and mortality. However, the determinants of cognitive dysfunction associated with heart failure are still unclear. We assessed the correlates of cognitive impairment among patients with heart failure enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association with cognition of demographic characteristics, objective tests and measures, medications, and comorbid conditions was assessed in 1511 patients with heart failure who had been admitted to 81 hospitals throughout Italy. Cognitive impairment was defined by a Hodkinson Abbreviated Mental Test score < 7. RESULTS: According to multivariate logistic regression modeling, age (per each decade: OR = 2.01; 95% confidence interval [CI] 1.72-2.35), the comorbidity score (OR 1.11; 95% CI 1.03-1.20), education (OR 0.88; 95% CI 0.84-0.2), low serum albumin (OR 1.78; 95% CI 1.35-2.34), sodium (OR 1.56; 95% CI 1.06-2.29), and potassium levels (OR 1.58; 95% CI 1.09-2.29), hyperglycemia (OR 1.33; 95% CI 1.02-1.73), anemia (OR 1.38; 95% CI 1.09-1.75), and systolic blood pressure levels > or = 130 mm Hg (OR 0.60; 95% CI 0.37-0.97) were independently associated with cognitive impairment, after adjusting for potential confounders. Among participants with abnormal laboratory findings on admission, restoration of normal glucose, potassium, and hemoglobin levels during hospital stay was associated with improved cognitive performance at discharge. CONCLUSIONS: Cognitive impairment among patients with heart failure is associated with several comorbid conditions, some of which are potentially treatable. This highlights the key role of comprehensive approach to the assessment and treatment of patients with heart failure.

Aged↗