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Cognitive dysfunction, negative symptoms, and tardive dyskinesia in schizophrenia. Their association in relation to topography of involuntary movements and criterion of their abnormality.

Little is known of factors that, on an individual basis, confer vulnerability to the emergence of involuntary movements (tardive dyskinesia) during long-term neuroleptic treatment. In this study of 88 chronic schizophrenic inpatients, 22 variables (four demographic, 14 medication history, and four features of illness) were compared for any association(s) with the presence, by differing topographies and criteria of abnormality, and severity of involuntary movements. Irrespective of the criterion used, the presence of marked cognitive dysfunction-muteness bore a consistent and highly significant primary association with both the presence and the overall severity of orofacial dyskinesia; no such association was found in relation to the presence of limb-truncal dyskinesia. Flattening of affect was the only other variable consistently associated with the presence of orofacial movements. The reliability and prominence of the association between the presence of orofacial, but not of limb-truncal, movements and cognitive dysfunction-negative symptoms suggest that these varying topographies may not constitute a unitary syndrome. This strong association, not with indexes of neuroleptic exposure but rather with features of the illness for which that treatment was prescribed, suggests some neurologic process, more subtle than may previously have been appreciated, as a vulnerability factor of some importance. In schizophrenia it appears to be intimately related to the disease process.

Adult

Treatment of cognitive dysfunctions and behavioral deficits in schizophrenia.

Integrated Psychological Therapy (IPT) is a structured intervention program that prescribes steps to remediate cognitive and behavioral dysfunctions that are characteristic of the psychopathology of schizophrenia. Evaluative studies of IPT indicated that the program improved schizophrenic patients' elementary cognitive processes such as attention, abstraction, and concept formation but that patients' performance was still below the normal range. The clinical utility of IPT will depend on studies that document the hierarchical generalization of improvements from the cognitive to the social and symptomatic levels of functioning.

Antisocial Personality Disorder

The Test for Severe Impairment: an instrument for the assessment of patients with severe cognitive dysfunction.

OBJECTIVE: To develop a reliable and valid test of cognitive function suitable for patients with severe cognitive impairment. DESIGN: Administration of a test; test-retest reliability; comparison to traditional test. SETTING: Chronic long-term-care facility. PATIENTS OR OTHER PARTICIPANTS: The participants were 40 elderly residents with severe cognitive impairment. MAIN OUTCOME MEASURES: Results of the Test for Severe Impairment (TSI) and its subsections (language, memory, executive function, and motor performance); correlation of test and retest scores; correlation of TSI with Mini-Mental State Exam. RESULTS: The TSI was significantly correlated with the Mini-Mental State Exam (r = 0.83, P less than or equal to 0.0001). Test-retest reliability was high (r = 0.96, P less than 0.0001). The internal reliability of the test was also good (alpha = 0.90). Preliminary result of a factor-analysis suggests that factor scores may be derived that relate to memory, language production, and knowledge of body parts. CONCLUSIONS: The TSI is a valid and reliable test of cognitive function in patients with severe cognitive impairment. It is appropriate to use it as a unified scale.

Aged

[Disseminated sclerosis: organic basis for mental disorders and cognitive dysfunction].

The MRI-(magnetic resonance imaging) scanner has improved the knowledge of the organic basis of cognitive defects in multiple sclerosis. Recent studies demonstrated a correlation of MRI-verified single lesions, atrophy of the corpus callosum and cognitive defects; but failed to demonstrate the convincing correlation between psychic symptoms and MRI-verified lesions.

Atrophy

Delayed hypoxic encephalopathy without cognitive dysfunction.

Three days after an episode of hypoxia, a 20-year-old man developed profound motor deficit in the absence of behavioral or cognitive disturbance. Previous reviews of delayed hypoxic encephalopathy have stressed behavioral and cognitive disturbances as the initial symptoms. This patient's pyramidal tract dysfunction in the absence of higher cortical dysfunction serves to illustrate that delayed hypoxic encephalopathy is predominantly a white matter rather than a gray matter disorder.

Adult

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia

Frontal-lobe cognitive dysfunction in conduct disorder adolescents.

Behavioral similarities between antisocial behavior disorders and frontal-lobe cerebral impairment have led to suggestions that conduct disorders are attributable to disinhibition deficit associated with frontal-lobe cerebral functions. This study compared the performance of 21 conduct disorder adolescents on measures of cognitive processes associated with frontal-lobe functions with that of a matched comparison sample. Conduct disorder adolescents performed more poorly on measures sensitive to frontal-lobe dysfunction (conceptual perseveration, poorly sustained attention, impaired sequencing on memory and motor tasks), but not on non-frontal-lobe specific cognitive measures. Although the findings support a neurobehavioral explanation of antisocial behavior as a product of cerebral disinhibition, caution is urged in overinterpreting causal relationships through neurobehavioral data.

Adolescent