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PubMed1998

[Relationship between cognitive function and discharge place among stroke patients after rehabilitation].

One hundred and ninety-nine elderly stroke patients, who received rehabilitation treatment, were examined, to clarify the relationship between cognitive function and discharge place. The patients who moved to long-term care facilities showed more severe disabilities of basic activities of daily living (ADL), more frequent incontinence, and lower functional impairments (Brunnstrom stage), compared with those discharged to their home. Multivariate regression analysis was done with discharge place as the dependent variable. Independent variables were age, sex, kind of stroke, rehabilitation period, level of ADL and IQ on Kohs test, or performance IQ on the Wechsler Adult Intelligence Scale. Older age, higher levels of ADLs, and higher scores on Kohs test IQ or Wechsler Adult Intelligence Scale Performance IQ were all significantly linked with home discharge. These results suggest that non-verbal cognitive dysfunction may affect discharge place in elderly stroke patients after rehabilitation therapy.

Activities of Daily Living↗

PubMed2001

Neuropsychological differences among empirically derived clinical subtypes of schizophrenia.

Neuropsychological profile differences between empirically derived clinical subtypes of schizophrenia were examined. Two hundred five patients and 209 demographically matched controls were administered a neuropsychological battery examining 8 domains. Subtypes included negative, disorganized, paranoid, Schneiderian, and mild. All subtypes displayed a neuropsychological profile of generalized impairment with greater deficits in learning, memory, and attention. Results were suggestive of diffuse cognitive dysfunction in schizophrenia with more severe deficits in learning and memory relative to executive skills. This pattern of greater learning and memory impairment was pronounced for disorganized patients. In contrast, paranoid patients outperformed disorganized and negative patients in several domains. These findings reflect bilateral frontal-temporal dysfunction, particularly in disorganized and negative patients. Subtype differences highlight the importance of conceptualizing schizophrenia as a multifocal disorder.

Adolescent↗

PubMed2004

Learning and memory impairment in rats with chronic atypical absence seizures.

Atypical absence seizures (AASs) represent a pediatric malignant seizure type that commonly exists as a component of Lennox-Gastaut syndrome. AAS involves both the hippocampal and thalamocortical circuitry in slow spike-and-wave discharges (SSWD) and is associated with cognitive dysfunction. The electrographic, behavioral, and pharmacological features of clinical AAS have been reproduced in rats chronically in the AY-9944 (AY) model. AY rats show spontaneous SSWD involving the hippocampus, a structure that is highly implicated in learning and memory. The purpose of the present study was to determine whether AY rats exhibit cognitive deficits that mirror those observed in AAS clinically. Hippocampal function was examined in AY animals both in vitro with electrophysiology (i.e., synaptic plasticity) and in vivo with a hippocampus-dependent radial arm maze (RAM) task that is designed to assess spatial cognition. In vitro tests of synaptic plasticity revealed impairments in long-term potentiation (LTP), paired-pulse facilitation (PPF), and presynaptic depression (PD). Consistently, performance of AY animals in RAM revealed fewer perfect entries, a greater number of errors, and required more training days to learn the task than saline-treated controls. The abolishment of spontaneous seizures by ethosuximide failed to recover the perturbed spatial learning and working memory in AY animals. AY rats demonstrate altered hippocampal functioning as manifested by altered synaptic plasticity and cognition. The relationship between AAS and cognitive deficit remains uncertain and the pathophysiology of both in AY treated requires further investigation.

Animals↗

PubMed2002

The ABC of Alzheimer's disease: cognitive changes and their management in Alzheimer's disease and related dementias.

Cognitive decline, commonly first recognized as memory impairment, is a typical feature of Alzheimer's disease (AD). Neuropathological changes in the cerebral cortex and limbic system lead to deficits in learning, memory, language, and visuospatial skills. The precise nature of cognitive dysfunction reflects the distribution of pathological changes in AD. These will vary along the disease severity continuum and may also depend on where the disease sits in the spectrum of dementia. For example, AD-related disorders such as Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) also show symptoms of cognitive decline and share several pathological features, including degeneration of cortical cholinergic and striatal dopaminergic neurons. In vascular dementia (VaD), there is often an unequal distribution of cognitive deficit, with severe impairment in some functions and relative sparing of others. Cholinesterase (ChE) inhibitors, which help restore acetylcholine levels in the brain, are licensed for the symptomatic treatment of AD and have shown additional benefit in related dementias. Physiological correlates of cholinergic function/dysfunction in the brain include regional cerebral blood flow, glucose metabolism, and cerebrospinal fluid levels of ChE enzymes. These variables represent valuable markers of the clinical efficacy of ChE inhibitors. However, direct assessment of cognitive improvement, stabilization or decline is usually considered the key efficacy parameter in clinical studies of ChE inhibitors in AD and related dementias. Large-scale, placebo-controlled clinical studies of ChE inhibitors have demonstrated efficacy in treating the cognitive impairments associated with AD. Randomized comparative studies of ChE inhibitors are now under way to directly compare symptomatic efficacy and effects on disease progression. Clinical trial data of the cognitive effects of ChE inhibitors in AD, LBD, PDD, and VaD are discussed in detail in this article. The benefits of long-term treatment on symptomatic improvement in cognition and further potential disease-modifying effects are highlighted.

Aged↗

PubMed2001

Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population.

BACKGROUND AND PURPOSE: The goals of the present study were to estimate the prevalence of acute impairments and disability in a multiethnic population of first-ever stroke and to identify differences in impairment and early disability between pathological and Bamford subtypes. Associations between impairments and death and disability at 3 months were identified. METHODS: Impairments that occur at the time of maximum neurological deficit were recorded, and disability according to the Barthel Index (BI) was assessed 1 week and 3 months after stroke in patients in the South London Stroke Register: RESULTS: Of 1259 registered patients, 6% had 1 or 2, 31.1% had 3 to 5, 50.6% had 6 to 10, and 10.6% had >10 impairments. Common impairments were weakness (upper limb, 77.4%), urinary incontinence (48.2%), impaired consciousness (44.7%), dysphagia (44.7%), and impaired cognition (43.9%). Patients with total anterior circulation infarcts had the highest age-adjusted prevalence of weakness, dysphagia, urinary incontinence, cognitive impairment, and disability. Patients with subarachnoid hemorrhage had the highest rates of coma. Patients with lacunar stroke had the high prevalence of weakness but were least affected by disability, incontinence, and cognitive dysfunction. Blacks had higher age- and sex-adjusted rates of disability in ischemic stroke (BI <20, odds ratio 2.76, 95% CI 1.47 to 5.21, P=0.002; BI <15, odds ratio 1.8, 95% CI 1.45 to 2.81, P=0.01) but impairment rates similar to those of whites. On multivariable analysis, incontinence, coma, dysphagia, cognitive impairment, and gaze paresis were independently associated with severe disability (BI <10) and death at 3 months. CONCLUSIONS: The extent of these findings indicates that an acute assessment of impairments and disability is necessary to determine the appropriate nursing and rehabilitation needs of patients with stroke.

Age Distribution↗

PubMed2004

[Postural imbalance in patients with vascular brain pathology].

Using MRI survey, 163 patients with various brain pathology of vascular genesis were studied. Vascular dementia according to NINDS-AIREN classification was diagnosed in 15% of patients. Cognitive disturbances in other patients did not reach a level of dementia. A control group comprised 61 subjects without rough structural changes on MRI and cognitive dysfunction. Motor disorders were estimated according to classification of J. Nutt et al. (1993), quantitative static changes were registered using computer stabilography. The results of the study showed that postural instability occurs in 100% of patients with vascular brain pathology. A degree of its expression elevated in direct proportion to the expression of cognitive disturbances, reaching a maximum in patients with dementia.

Adult↗

PubMed1997

The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Measurement of cognitive dysfunction in the early stages of Alzheimer's disease (AD) has been well studied and there are many objective tests in use for this purpose. However, with the exception of clinical rating scales, such as the Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging, there are few objective measures of cognition in the more advanced stages of AD. Given a renewed interest in potential AD therapies, objective measures of mental functioning are needed to adequately assess change in more advanced AD patients. As part of an effort by the NIA-Alzheimer's Disease Cooperative Study to evaluate new measures of efficacy for their utility in treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year evaluation of change across a wide range of AD severity. The data suggest that the SIB is a reliable and valid measure of progression, particularly in persons with moderate to severe AD. The SIB may therefore be a useful outcome measure in clinical trials that include patients with more advanced stages of AD.

Aged↗

PubMed2006

Chronic migraine prevention with topiramate.

Chronic migraine (CM) is a disabling condition with not many treatment strategies available. Topiramate is effective in episodic migraine prevention, however little is known about its effect in CM. An open label study was performed. Sixty-four patients diagnosed with CM or probable CM according to the IHS diagnostic criteria were enrolled, 50 patients were available for analysis and an intention-to-treat methodology was applied. The primary endpoint considered was the number of patients with a decrease in headache frequency higher than 50%. The median dose was 100 mg, a reduction in frequency higher than 50% occurred in 33 patients (66%) and 14 (28%) presented a complete response, defined as a frequency reduction higher than 95%. The medication was well tolerated. The most common side effects found were weight loss, paraesthesias, nausea, cognitive dysfunction, fatigue, somnolence, insomnia and depression. Our findings suggest that topiramate is effective in CM prophylaxis.

Adult↗

PubMed2006

Depression as prognostic factor: 6 months follow-up in a geriatric institution.

Depression in the elderly and especially in the demented elderly is common, but it is unclear to what extent depression affects the prognosis of dementia. We performed a 6 months follow-up on the elderly to evaluate the effect of depression on the prognosis of dementia. Among the residents in a Korean geriatric institution, a total of 141 elderly residents were included in this study. Those residents who had geriatric depression scale (GDS) scores over 20 were considered as having depression. The subjects were assessed at baseline and at 6 months later with the Korean Mini-Mental State Examination (K-MMSE), Clinical Dementia Rating (CDR) and Barthel index (BI). For all the 141 subjects, the changes of the K-MMSE, CDR and BI scores were first compared between the depressed and non-depressed groups. Then, for the 58 depressed subjects subdivided into three groups (36 subjects in the non-demented group, 14 subjects in the Alzheimer disease (AD) group and 8 subjects in the vascular dementia (VaD) group), the changes of the scores among the three groups were compared. For all subjects, the changes of the K-MMSE and CDR scores were more severe in the depressed group than in the non-depressed group. For the 58 depressed subjects, the changes were significantly different among the three groups (p=0.02 for the K-MMSE, p<0.001 for the CDR), and the changes were the most severe in the VaD group. For the elderly, depression has a significant influence on the cognitive deterioration. Moreover, the effect of depression on the cognitive dysfunction and on the prognosis of dementia is more severe in the demented elderly, and especially for the VaD patients.

Aged↗

PubMed2006

Adult rat's offspring of alcoholic mothers are impaired on spatial learning and object recognition in the Can test.

The aim of this study was to examine spatial and object recognition reference and working memory in adult offspring of Wistar rats exposed to ethanol in prenatal and/or preweaning period. For this purpose, four different conditions of the Can test were performed sequentially: spatial/object discrimination task, spatial orientation task, simple object recognition task and complex object recognition task. The results of present study shows: (1) the significant impairment in spatial learning and object recognition in animals exposed to alcohol during prenatal and/or preweaning period, (2) that cognitive dysfunction become increasingly evident with switching from simple to more sophisticated task, (3) that the most vulnerable period is the early neonatal period which corresponds to the third trimester gestational development in humans and (4) that during the developmental period, abrupt introduction or withdrawal of ethanol, rather than its continuous consumption, can produce higher cognitive deficit later on. In conclusion, moderate ethanol exposure during brain development produce long lasting impairment of spatial and recognition reference and working memory in adult rat's offspring and these effects depend on the developmental period in which they were exposed to ethanol.

Age Factors↗

PubMed1996

A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results.

PURPOSE: To evaluate the effects of limited field conventional cerebral radiotherapy (RT) on cognitive functions of adults. METHODS AND MATERIALS: A prospective neuropsychological study was performed on 17 patients who underwent conventional limited field RT for a low-grade glioma or for a good-prognosis anaplastic glioma. Results were compared with 14 control patients with low-grade gliomas who did not receive radiotherapy. RESULTS: A transient significant decrease of performances for the Reaction Time test was observed at 6 months in the irradiated group with return to baseline values 12 months post-RT. Subsequently, no other significant changes were observed over a 48-month follow-up period in the irradiated and nonirradiated groups. Nonetheless, when the scores of each patient were considered over time instead of the mean values of the group, one irradiated patient (5.8%) experienced progressive deterioration while two irradiated patients (11.7%) experienced long-lasting improvement. Individual changes did not occur in the control group. CONCLUSION: This study suggests that a transient early delayed drop of neuropsychological performances at 6 months is frequent following limited field conventional RT, but the risk of long-term cognitive dysfunction after irradiation is low, at least in the first 4 years after RT and when it is administered alone in young adults.

Adolescent↗

PubMed2003

Hopelessness, neurocognitive function, and insight in schizophrenia: relationship to suicidal behavior.

Insight and hopelessness have been reported to be associated with suicidality in schizophrenia. In addition, there is evidence that diminished insight is correlated with impairment in some domains of cognitive function in schizophrenia. The purpose of this study was to clarify the relative importance for suicidality in patients with schizophrenia of hopelessness, cognitive dysfunction, and insight. This study included 333 patients with chronic schizophrenia who were prospectively studied. Insight was rated by the insight items from the Schedule for Affective Disorders and Schizophrenia (SADS) and the Hamilton Depression Rating Scale (HDRS). Positive, negative, and anxiety-depression symptoms were measured with the Brief Psychiatric Rating Scale (BPRS). Cognition was assessed with a neurocognitive battery, which included measures of attention and psychomotor speed, verbal fluency, verbal memory, working memory, and executive function. Current and lifetime suicidality was prospectively assessed. Hopelessness, substance abuse, and greater insight were associated with attempted suicide and suicidal ideation. Those with a history of lifetime, but not current, suicidality had better function on tests of psychomotor speed and attention, verbal working memory, verbal fluency, verbal memory, and executive function. Neurocognitive measures were not significantly correlated with hopelessness and insight. Hopelessness was more severe in those with current and lifetime suicidality. A multiple regression analysis was used to predict current and lifetime suicidality from hopelessness, substance abuse, insight, and cognitive factor scores. The regression models predicting current and lifetime suicidality indicated that hopelessness was the most important predictor of both (beta=0.41, p=0.0001; and beta=0.35, p=0.01, respectively). These findings suggest that hopelessness, substance abuse, greater insight into illness, and higher cognitive function are associated with greater suicidality in chronic schizophrenia, but that among these, hopelessness may be the principal predictor of suicidality.

Adolescent↗

PubMed1997

Neuropsychological profiles in schizophrenia: paranoid versus undifferentiated distinctions.

Research on schizophrenia has searched for subtype-specific cognitive dysfunction to elucidate the neurodevelopmental underpinnings of the disorder. The neuropsychological distinctions between 21 paranoid and 15 undifferentiated schizophrenics were studied. The paranoid group had significantly better Verbal IQ, executive functioning on the Wisconsin Card Sorting Test, and memory for spoken language on the Sentence Repetition Test compared to undifferentiated schizophrenics. While the paranoid subtype showed trends toward better performance on a wide variety of tasks, both subtypes showed impairments on tasks requiring continuous auditory attention and fine motor speed and coordination. Despite the paranoid subjects' more intact verbal skills, both groups showed significant deficits in verbal learning on the Rey Auditory Verbal Learning Test. This suggests that temporal-hippocampal system dysfunction may be a common denominator in both schizophrenic subtypes. These findings were not accounted for by subtype differences in the level of education, depression or severity of illness.

Adult↗

PubMed2006

(R)-3'-(3-methylbenzo[b]thiophen-5-yl)spiro[1-azabicyclo[2,2,2]octane-3,5'-oxazolidin]-2'-one, a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist displays cognitive enhancing properties.

Recent studies have suggested that the alpha7 nicotinic acetylcholine receptors play important roles in learning and memory. Herein, we describe our research of the structure-activity relationships (SAR) in a series of (S)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin]-2'-ones bearing various bicyclic moieties to discover novel alpha7 receptor agonists. Through a number of SAR studies on the series, we have found out that inhibition of CYP 2D6 isozyme, which was a primary obstacle for the previously identified compound, was avoidable by the introduction of bicyclic moieties. Chemical optimization of the series led to the identification of a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist 23. This compound not only possessed high binding affinity (K(i) = 3 nmol/L) toward the alpha7 receptor but also showed agonistic activity even at a concentration of 0.1 micromol/L. In addition, compound 23 improved cognition in several rat models, which might suggest the potential of the alpha7 receptor partial agonist for the treatment of neurological disorders including cognitive dysfunction.

Animals↗

PubMed1997

Vascular dementia, hypertension, and the brain.

Ischemic vascular dementia is a clinical syndrome of acquired intellectual impairment with ischemic cerebral injury resulting from occlusion of cerebral blood vessels and loss of cerebral tissue caused by cerebrovascular disease. With increasing life expectancy, the developed countries have experienced a shift towards a progressively older population. As the average age of the population increases, the prevalence of cerebrovascular disease and vascular dementia is likely to increase. The risk of vascular dementia seems to be correlated with the epidemiologic risk factors of stroke, namely hypertension. Hypertension is thought to be directly associated with vascular dementia and preliminary evidence suggests an association between elevated blood pressure and impairments in cognitive functioning. Recent investigations have found significant associations between hypertension and cerebral dilation and left hemisphere atrophy, and an increased incidence of white matter hyperintensities among hypertensives. Treatment and prevention of vascular dementia and cognitive dysfunction in the elderly require attention to cerebrovascular risk factors, particularly hypertension. Vascular dementias are potentially preventable and cases of Alzheimer's disease with vascular components are becoming increasingly recognized.

Brain↗

PubMed2006

The alcoholism generator.

Alcohol exposure largely affects 3 populations: fetuses, adolescents, and adults. These 3 developmental stages are inextricably intertwined such that elevated alcohol exposure at any time increases the probability of exposure at the others. This circular interdependency is called the alcoholism generator. Furthermore, exposure to large amounts of alcohol at these 3 times can cause cognitive dysfunction, largely through mechanisms of alcohol-induced perturbations in neurogenesis and synaptogenesis. Breaking this cycle is key to reducing problem alcohol drinking and the associated sequelae.

Adolescent↗

PubMed1997

Cognitive impairment in adolescents with schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age = 15.71 years) was compared with that of 17 normal adolescents (mean age = 15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory.

Adolescent↗

PubMed1999

Emotional and cognitive aspects in adolescence-onset school difficulties.

Learning disorders in adolescence can become a significant risk factor for psychopathology. The paper investigates emotional and cognitive patterns in adolescents with learning disorders. The first part of the study describes the impact of child-onset learning disorders on adolescence passage. In the second part four clinical conditions that can determine adolescence-onset learning disorders are outlined. These are adolescent turmoil, intellectual inhibition, delay in reasoning development and metacognitive dysfunctioning. Cognitive, emotional and behavioral features of these conditions are discussed, in terms of diagnostic and therapeutic implications.

Adolescent↗