SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We describe a familial disorder consisting of sleep apnea, anosmia, colorblindness, partial complex seizures, and cognitive dysfunction. The phenotypic expression of the syndrome suggests an autosomal dominant inheritance with incomplete penetrance.
OBJECTIVES: Based on the national Canadian Study of Health and Aging (CSHA), to compare 5-year overall mortality and causes of death in elderly with and without dementia. To determine how frequently dementia was mentioned on the death certificate. METHODS: For people who underwent a clinical examination in 1991 (n = 2,923), overall and cause-specific mortality rate ratios were calculated by dementia status (AD; vascular dementia; other dementias/other cognitive impairment; and normal cognition), age group (65 to 74, 75 to 84, 85+ years), and sex, using the Canadian general population as the reference. Similar rate ratios were calculated for people in the community who screened negative for cognitive impairment and who did not undergo a clinical examination (n = 7,340). Among elderly diagnosed as having AD or vascular dementia through the CSHA and who later died, it was determined how frequently dementia was recorded on the death certificate. RESULTS: The subgroup without cognitive dysfunction had a survival rate similar to that of the overall Canadian population except in the oldest age group, where the survival rate was better than that of the general population, which includes people with dementia. People in the three groups with cognitive impairment had a poorer survival in all age/sex groups than those without cognitive impairment and the general Canadian population. The most common causes of death in all groups were from vascular diseases. People with vascular dementia had the highest relative mortality rates for heart and cerebrovascular disease. Most of the AD groups also had high relative vascular system mortality rates. Among patients clinically diagnosed with AD, only 14.3% had any dementing illness recorded as the underlying cause of death; 41.8% had any dementing illness recorded anywhere on the death certificate. For vascular dementia, the corresponding numbers were 5.8% and 23.3%. CONCLUSION: Elderly with dementia have clearly increased mortality rates relative to elderly without cognitive impairment in all age/sex categories. People with vascular dementia have a particularly poor prognosis. Studies of AD and vascular dementia using death certificate data will grossly underestimate the proportions of elderly with these diseases.
The new questionnaire Euroquest was designed to study effects from exposure to organic solvents, and it covers the most commonly reported symptoms associated with long-term solvent exposure. Its convergence and criterion validity were evaluated by means of comparison with the two well-established generic symptom questionnaires Symptom Checklist (SCL-90) and General Health Questionnaire (GHQ-30). Men with long-term exposure to organic solvents and symptoms common in toxic encephalopathy (TE) classified as TE type 2A (n=29) or 2B (n=28) according to their neuropsychological test performance, and a comparable group of non-exposed healthy referents (N=57), were included. The six Euroquest factors obtained by a factor analysis were labeled: 'emotional lability' 'cognitive disturbances' 'peripheral neurology' 'sleepiness' 'fatigue' and 'sleep disturbances'. These factors correlated well with most SCL-90 scales and with the GHQ-30 total score in the combined TE groups. The combined TE groups were correctly classified to a similar degree by the Euroquest factors 'cognitive disturbances' and 'peripheral neurology' (TE 82.5% and referents 93%) and the SCL-90 scales 'somatization, 'interpersonal sensitivity', 'obsessive-compulsive symptoms' and 'hostility' (TE 84.2% and referents 93.0%), but not as well by GHQ-30 (TE 61.4% and referents 79%). In comparison with the separate TE groups most referents, and a considerably higher percentage of 2B than 2A subjects, could be correctly classified with both Euroquest and SCL-90. With GHQ-30, only a few 2A cases and fewer than half of the 2B cases were correctly classified. In conclusion, the Euroquest factors converged with both SCL-90 scales and GHQ-30 score. With both the Euroquest and SCL-90 questionnaires a similar percentage of the TE subjects were discriminated from the referents, most conspicuously regarding TE 2B subjects, who had an objectified cognitive dysfunction. In a choice between Euroquest and SCL-90, the Euroquest may have the advantage of higher face validity, for TE subjects.
AIM: This study sought to determine the relationship between behavioural and psychopathological disturbance and the functional status of dementia patients. METHOD: The link between results of the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) and Multidimensional Observation Scale for Elderly Subjects (MOSES) with cognitive impairment in 23 demented and 30 non-impaired nursing home residents was examined. Diagnosis of dementia was based on ICD-10 criteria. RESULTS: Results showed that behavioural and psychotic symptoms were most often found in cognitively impaired residents. Several symptoms of behavioural pathology showed associations with lower cognitive status, including delusions, apathy and aberrant motor behaviour. But dementia was not associated with more aggressive behaviours. CONCLUSION: Results of NPI-NH were correlated significantly with the MOSES scale in both groups. The results suggest that some non-cognitive symptoms may be related to the cognitive dysfunction in dementia and behavioural pathology may also have impact on the patient's ability to function.
Impairment on visual naming tests is relatively common among temporal lobe epilepsy (TLE) patients. Recent reports suggested that the ability to name objects on the basis of their descriptions is an even more sensitive and perhaps more ecologically valid measure of naming problems among left hemisphere TLE patients. To further explore the nature of dysnomia in TLE, the current study assessed a group of patients with either left or bilateral TLE (n=16) and a group of healthy controls (n=11) on computerized measures of naming to description or auditory naming (AN) and visual naming (VN). Both speed and accuracy scores on AN distinguished patients from controls better than VN scores. There was a trend for AN speed, but not other naming test variables, to be associated with self-reported word finding problems. AN speed and accuracy, but not VN scores, correlated significantly with a broad range of other cognitive test scores. In summary, AN speed and accuracy are sensitive indexes of cognitive dysfunction in TLE patients. AN may be an appropriate analogue of the word finding demands of conversational speech because of its multiple neuropsychological demands. These results provide further evidence of the potential value of AN assessment in TLE patients. Further study of the cognitive processes required during AN, its relation to word finding problems in discourse, and the effect of anterior temporal lobectomy on this ability is warranted.
"Atypical" antipsychotics represent a new generation of antipsychotics with a significantly lower incidence of extrapyramidal side effects (EPS), as well as little or no effect on prolactin elevation. These advantages constitute a major improvement in the treatment of patients with schizophrenia. The exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or D4 receptors, or a more rapid dissociation from the dopamine D2 receptor, may account for atypicality. Although the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have come to the fore. Thus, the challenges are far from over. The current atypicals are much more effective against the psychosis of schizophrenia than against the other, more enduring aspects of this disorder, e.g. negative symptoms and cognitive dysfunction. At present, the atypicals use a "pharmacological shotgun" strategy to treat aspects of the disease in all patients. A more sophisticated and perhaps effective approach to schizophrenia may lie in independently targeting the pathophysiological mechanisms of each clinical dimension (i.e. positive, negative, cognitive, and affective) with more selective drugs that can be combined and individually titrated to the needs of each patient.
INTRODUCTION: Recent studies have suggested that the presence of persistent cognitive dysfunctions in bipolar patients is not restricted to acute episodes, but they persist even during remission states. Nevertheless, there are several methodological pitfalls in most studies, such as unclear remission criteria, diagnostic heterogeneity or small sample sizes. PATIENTS AND METHODS: Several domains of cognitive function were examined in 30 depressed bipolar patients [DSM-IV criteria for major depression, Hamilton Depression Scale (HDRS) > or =17] and 30 euthymic bipolar patients (at least 6 months of remission, HDRS < or =8 and Young Mania Rating Scale, YMRS < or =6). Psychosocial functioning was assessed through General Assessment of Functioning. RESULTS: The two groups showed a similar pattern of neuropsychological performance. However, the depressed group was significantly impaired on the Controlled Oral Word Association Test, FAS (COWAT), a measure of verbal fluency, compared with the euthymic group. On the other hand, functional outcome in euthymic patients was related to verbal fluency, even after controlling for residual depressive symptoms. CONCLUSIONS: Neuropsychological performance was similar in both groups, except for verbal fluency, which was lower in the depressed group. Poor verbal fluency was related to a poor social outcome in euthymic patients. Further research including longitudinal designs aimed at evaluating changes in cognition in these patients is warranted.
Following our initial report of the insidious development of reversible, valproate-induced hearing, motor, and cognitive dysfunction in two patients, we evaluated 36 patients in an epilepsy clinic who had been taking therapeutic levels of valproate for at least 12 months; 29 of these patients were examined according to a prospective protocol. We observed varying degrees of parkinsonism and cognitive impairment, from none to severe. Discontinuation of valproate in 32 affected patients led to subjective and objective improvement on follow-up testing at least 3 months later. Improvement was greatest in patients who were affected most. We conclude that a syndrome of reversible parkinsonism and cognitive impairment may develop insidiously in patients who have been treated with valproate for more than 12 months. The association with valproate may be overlooked due to the insidious onset.
BACKGROUND AND PURPOSE: We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS). METHODS: Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis. RESULTS: All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment. CONCLUSION: The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.
Propentofylline (Karsivan, Hoechst Roussel Vet) is a selective inhibitor of adenosine transport and phosphodiesterase. For several years it has been well established in the geriatric therapy of the dog improving hemodynamics in cerebral and peripheral compartments. In human medicine clinical development of this pharmaceutical has already entered an advanced stage for the long-term therapy of patients with Alzheimer's disease and vascular dementia. In the brains of senile dogs and in human patients suffering from Alzheimer's disease comparable neuropathological findings can be made. In senile dogs a distinctive correlation exists between the quantity of beta-amyloid accumulation and the degree of dementia. The extension of knowledge by clinical studies in humans and by experimental studies in animals may contribute to a deeper understanding of therapeutical approaches of cognitive dysfunction in the old dog. The xanthine derivative propentofylline [1-(5'-oxohexyl)-3-methyl-7-propylxanthine] directly interfers with the neurodegenerative process and reduces the extent of damage to brain structures. In experimental models of vascular dementia and/or Alzheimer's disease it improves cognitive functions, inhibits inflammatory processes as well as excessive activation of microglia, formation of free radicals, cytocines and abnormal amyloid precursor proteins (APP). It stimulates synthesis and liberation of nerve growth factor (NGF) and reduces ischemic damage to the brain. In clinical studies in humans it improved cognitive functions as well as global functions and the ability to cope with tasks of routine daily life in patients suffering from Alzheimer's disease and vascular dementia.
Data were gathered regarding the associates of chronic fatigue syndrome (CFS) with: (1) speed of cognitive processing, (2) motor speed, (3) ability to sustain attention, and (4) mood. Patients were given a brief neuropsychological test battery before and after double-blind treatment with terfenadine or placebo and completed a daily mood rating scale (Positive and Negative Affect Schedule) during the study. CFS patients exhibited slower cognitive processing and motor speed and lower positive affect, as compared to data reported from previous studies of healthy subjects and other patient groups; however, CFS patients did not exhibit deficits in sustained attention in comparison to other groups. The CFS patients' ability to attend to verbal versus figural stimuli and mood ratings were different from those reported in studies of patients with depression. Because of methodological limitations, these findings are preliminary, but they encourage further assessment of cognitive dysfunction and mood in CFS.
Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.
SIB-1553A ((+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thiophenol HCl) is a neuronal nicotinic acetylcholine receptor (nAChR) ligand which is active in rodent and primate models of cognition. In functional assays, SIB-1553A exhibits marked subtype selectivity for nAChRs as compared to nicotine. In addition SIB-1553A also exhibits affinities to histaminergic (H3) and serotonergic (5-HT1 and 5HT2) receptors and sigma binding sites. In the present investigation, we characterized SIB-1553A-induced neurotransmitter release in vivo. Following subcutaneous injection (s.c., 10 mg/kg), SIB-1553A rapidly entered the brain achieving concentration of approximately 20 microM 15 min post-injection and was eliminated from plasma with a terminal half-life of approximately 32 min. In freely moving rats, SIB-1553A (1-40 mg/kg, s.c.), markedly increased ACh release in the hippocampus and prefrontal cortex. In both regions, the magnitude of SIB-1553A-induced ACh release was greater than that seen with the prototypical nAChR agonist, nicotine (0.4 mg/kg, s.c.). Both isomers of SIB-1553A induced similar levels of increase in hippocampal ACh release. Increased hippocampal ACh release was also observed following oral administration of SIB-1553A (40 mg/kg) or after local perfusion into the hippocampus (1 mM). SIB-1553A-induced hippocampal ACh release was significantly attenuated by two nAChR antagonists, mecamylamine (MEC) and dihydro-beta-erythroidine (DHbetaE), and by the dopamine (DA) (D1) antagonist, SCH-23390, arguing that ACh release, in part, involves activation of nAChRs and a permissive DA synapse. In contrast to its robust effects on ACh release, SIB-1553A (40 mg/kg, s.c.) modestly increased striatal DA release (approximately 180% of baseline). Due to the proposed role of cholinergic pathways in learning and memory, the neurochemical profile of SIB-1553A suggests a potential for it to treat cognitive dysfunction.
The relative value of animals with memory impairments, due either to experimental lesions or aging processes, is dependent upon the specific hypothesis being tested. The experimental approaches described in the preceding reviews are valuable for basic studies on learning and memory in the mammalian brain. However, because of important differences between available model systems and human disease states, such as Alzheimer's disease, their use at present may be insufficient for understanding and developing treatment strategies for human cognitive dysfunctions. In this commentary, different aspects of animal models of memory dysfunction will be discussed relative to their ability to assess the structural and functional consequences of central nervous system (CNS) repair.
In this study, we examined executive functions and visual prototype learning in patients with schizophrenia (n=22) and matched healthy control subjects (n=20). The patients demonstrated marked perseveration in the Wisconsin Card Sorting Test (WCST), whereas they successfully learned prototypes of dot-pattern category exemplars. These findings are against the hypothesis of a pure generalized cognitive dysfunction in schizophrenia, providing preliminary evidence for intact neocortical mechanisms related to perceptual classification functions.
We assessed the effect of diabetes and of episodes of severe hypoglycaemia on cognitive function in 28 diabetic children. Fifteen diabetic children (age 12.9 (SD 2.0) years) had experienced 1-4 episodes of severe hypoglycaemia. Five of these children diseased before the age of 5 years (SH-eod subgroup), and ten diseased after this age (SH-lod subgroup). Thirteen diabetic children (age 13.1 (SD 2.0) years) had not experienced episodes of severe hypoglycaemia (non-SH group). Each diabetic child was compared with a healthy control child of the same age and gender and with a similar social background. Neuropsychological assessment was blinded. The neuropsychological tests were grouped into one of seven cognitive domains. We found no effect on cognitive performance from diabetes per se or from severe hypoglycaemia in children with late-onset diabetes. However, early-onset diabetes was associated with low scores in two cognitive domains: psychomotor efficiency and attention. The SH-eod subgroup had lower scores than the SH-lod subgroup in psychomotor efficiency (p < 0.05) and also had lower scores than the SH-lod subgroup and the non-SH group in measures of attention (p < 0.05). Our results may indicate a slight cognitive dysfunction in children with early-onset diabetes who have experienced episodes of severe hypoglycaemia early in childhood.
The hypothesis that lymphocytotoxic antibodies are associated with neuropsychiatric involvement in systemic lupus erythematosus (NP-SLE) is re-evaluated in this study. In an unselected cohort of 98 women with SLE a cross-sectional study has been performed to analyse associations among standardised clinical, neurological, and neuropsychological assessments and lymphocytotoxic antibodies measured by microcytotoxicity assay. Fifty patients showed objective clinical evidence of continuing or past NP-SLE and 54 patients had cognitive impairment. In accordance with previous observations 44% (24/54) of the cognitively impaired group did not have clinically detectable evidence of NP-SLE. Although lymphocytotoxic antibodies were found to be only marginally more prevalent in those patients with a clinical diagnosis of NP-SLE than in those without (32% v 23%), these antibodies were significantly associated with cognitive impairment (chi 2 = 5.42; p less than 0.02). No association was detected between lymphocytotoxic antibodies and either overall systemic disease activity or other organ system involvement, suggesting that the association between lymphocytotoxic antibodies and cognitive dysfunction in SLE is specific.
Three female patients (ages 32, 37 and 27 years) developed progressive deficits of cognition in stages of multiple sclerosis in which physical disability ratings were low. Neuropsychological examination revealed severe cognitive impairments in the first two patients. Cognitive functioning was essentially intact in the third patient, although her work pace was significantly slowed. CT scanning of the brain showed cortical atrophy as well as white matter lesions in patients 1 and 2, and multiple lesions and oedema of predominantly white matter in patient 3. The differences of cognitive dysfunction between the third and the first two patients may be related to involvement of different anatomical structures.