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Late magnetic resonance imaging related to neurobehavioral functioning after aneurysmal subarachnoid hemorrhage.

Twenty patients who underwent early aneurysm surgery--that is, surgery within 72 hours after rupture--underwent further follow-up examination including magnetic resonance imaging (MRI) of the brain and a comprehensive neuropsychological assessment. Significant statistical correlation between tissue loss as seen on a late MRI scan and neurobehavioral deficits could not be established. Among 9 patients with no tissue loss seen on MRI, 3 exhibited substantial cognitive dysfunction and 6 had mild impairment. Three patients showed minor but corresponding tissue loss and deficits. In 3 patients with pronounced pathological indications on MRI, evidence of cognitive dysfunction was absent in 2, and 1 patient showed substantial impairment. The remaining 5 individuals displayed moderate pathological indications on MRI, with no obvious correspondence to cognitive functioning. In 7 patients, small white matter lesions, probably silent infarcts not seen on computed tomographic scan, were discovered on MRI. There was a clear relationship between arterial hypertension prior to aneurysm rupture and the extent of tissue loss seen on MRI. Absence of pathological findings on MRI scan did not exclude cognitive malfunctioning, and vice-versa.

Adult↗

Neuropsychological and biomedical assessment of depression-dementia syndromes.

Evaluating the clinical significance of cognitive dysfunction in patients who exhibit signs of both depression and dementia is one of the more formidable challenges in psychiatry. This article reviews cognitive dysfunction associated with depression, the concept of "pseudodementia," and the syndromal phenomenology of coexisting depression and Alzheimer's-type dementia. The state of the art in neuropsychologic, electroencephalographic, metabolic, and neuroradiographic techniques for evaluating dementia and depression syndromes will be discussed, as will implications for the treatment of such patients.

Aged↗

[Early experience, stressful dysregulation of the hormonal axis and age-related vulnerability to neurodegenerative processus: a longitudinal study in the rat].

The deleterious effects of particular environmental situations have been suspected to augment the repercussions of cerebral injuries leading to increased vulnerability during ageing. The relationship between the hormones of the hypothalamo-pituitary-adrenal axis, mainly glucocorticosteroids, and cerebral structures like the hippocampus has been the subject of intense investigation in the recent years. Data suggest that long-term elevated blood levels of these hormones can induce neuronal alterations leading to cognitive dysfunction. This hypothesis has been tested with relevant animal models of normal/abnormal ageing. The models are based on the existence of considerable inter-individual differences in the degree of age-related cognitive impairments observed in rodents. Results show that long-term glucocorticosteroid exposure induces cerebral changes related to the action of these hormones on their central receptors. Experimental data are in accordance with clinical investigations suggesting that hormonal changes, and chronic life events, could be considered as a predictive factor of future cognitive dysfunction.

Aging↗

Psychopathology and pain in medical in-patients predict resource use during hospitalization but not rehospitalization.

The authors investigated the relationship between psychopathology and resource use in general medical in-patients during hospitalization and rehospitalization. Between 1 July 1987, and 30 April 1989, 1020 in-patients were prospectively screened for depression, anxiety, cognitive dysfunction, and pain. Overall, the screen identified 47% of patients as having high psychopathology or pain, including 25.7% depressed, 21.8% anxious, 17.6% with cognitive dysfunction, and 5.2% with high pain. There were no measured differences in demographics or disease severity between high and low psychopathology groups. High psychopathology patients had longer stays and higher costs during the index hospitalization but there were no differences during subsequent hospitalizations. Length of stay declined overall during the study period, but there were no changes over time in the association between high psychopathology or pain with increased resource use. The measured symptoms of psychopathology and pain we measured are associated with increased short-term utilization of health care resources, but the increase does not extend to subsequent hospitalizations. Outcome studies aiming to reduce psychopathology in medical in-patients should pay particular attention to short term costs.

Anxiety Disorders↗

The cycle of schizoaffective disorder, cognitive ability, alcoholism, and suicidality.

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-TV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a history of suicide attempts or suicidal ideation. Discriminant analysis was used to identify cognitive test performance measures that distinguished those with versus those without suicidal behavior. None of the cognitive measures discriminated between the two groups. The rates of suicidal behavior (suicidal ideation and suicide attempts) did not differ between participants with versus those without comorbid alcohol use. An association was found between suicidal behavior and the diagnosis of schizoaffective disorder. It was concluded that the history of prominent mood syndromes characteristic of schizoaffective disorder contributes to increased risk of suicidal behaviors. Cognitive dysfunction and/or alcoholism did not contribute additionally to risk in this study.

Adult↗

Cognition in mania and depression: psychological models and clinical implications.

Affective disorders, including bipolar disorder and major depressive disorder, are highly prevalent throughout the world and are extremely disabling. Diagnostic and Statistical Manual criteria and psychological models strongly implicate cognitive dysfunctions as being integral to our understanding of these disorders. We review the findings from studies that have used neurocognitive tests and functional imaging techniques to explore abnormal cognition in affective disorders. In particular, we highlight the evidence for cognitive dysfunctions that persist into full clinical remission, and the recent trend toward the use of "hot" processing tasks, involving emotionally charged stimuli, as a means of differentiating between the cognitive underpinnings of mania and depression. The clinical relevance of these developments is discussed.

Affect↗

The role of cognition in vocational functioning in schizophrenia.

Schizophrenia is associated with long-term unemployment. Cognitive dysfunction, rather than clinical symptoms, may be the most important factor in the ability to work for patients with this disorder. To evaluate the relationship of clinical symptoms and cognitive functioning to work status, thirty patients with schizophrenia, who were participants in a vocational rehabilitation program, were evaluated with a comprehensive neuropsychological battery and assessment of psychopathology. Subjects were classified as being in stable full-time, part-time or unemployed work status for at least a year. Univariate analysis indicated that patients who were working full-time were significantly better educated, more likely to be treatment-resistant, more likely to be treated with an atypical antipsychotic medication, had more positive symptoms, and were engaged in work tasks which were more cognitively complex than the part-time employed and unemployed work groups. An ANCOVA controlling for education demonstrated that the full-time employed group performed significantly better than the unemployed group on measures of executive functioning, working memory and vigilance; and significantly better than the part-time group on measures of vigilance and executive functioning. Although negative symptoms did not significantly relate to work status in the univariate analysis, a multiple regression indicated that negative symptoms, level of education, and executive functioning differentiated the work groups. These results suggest that poor premorbid function, negative symptoms and cognitive dysfunction are significantly associated with unemployment in schizophrenia.

Adult↗

Hyperlithemia correction and persistent delirium.

Experience with three patients whose courses are described suggested that delirium and persistent neurologic dysfunction follow rapid correction of hyperlithemia, which develops after regular lithium doses. From all retrievable published reports of adult hospitalization for hyperlithemia, all cases that described cognitive dysfunction after lithium administration for at least 10 days with insubstantial neuroleptic exposure were selected. Lithium was universally discontinued before or on admission. Of the 65 such cases, 50 were at least somewhat responsive on admission; of these, substantial deterioration during hospitalization occurred in 56%. Dialysis was associated with greater incidence of persistent neurologic sequelae (62% vs. 22%, P = .012) and deterioration during hospitalization (85% vs. 46%, P = .016), although cognitive dysfunction on hospital admission was less (P < .001) for patients who were then dialyzed. The greater neurotoxicity after dialysis suggests that while hyperlithemia can be toxic, its rapid correction can be more toxic. Parallels with hyponatremia, including a potential mechanism, suggest that gradual rather than abrupt correction of hyperlithemia might decrease the risk of neurotoxicity.

Aged↗

The clinical implications of cognitive impairment in elderly patients with chronic heart failure.

The purpose of this study was to examine whether cognitive dysfunction was associated with poor participation in an outpatient treatment program for patients with chronic heart failure and if it was related to specific patient characteristics. Cognitive function was measured with the Mini Mental State Examination (MMSE). Twenty-three of 78 (29%) patients randomized to structured care did not participate in this program and nonparticipation during 6-month follow-up was associated with an MMSE score below the median and a low calculated creatinine clearance (CrCl) (R2=0.15, p=0.0025) at entry. In the entire group long duration of heart failure and low blood hemoglobin concentration were independently associated with an MMSE score below the median at entry (R2=0.14, p < 0.0001). Among elderly patients hospitalized with moderate-severe chronic heart failure, judged to be eligible for a nurse-directed outpatient program after discharge, a low MMSE score predicted nonparticipation in such a program. Cognitive dysfunction, which was related to the duration of heart failure, should be evaluated in the treatment of patients with chronic heart failure.

Aged↗

Anesthesia, the brain, and cardiopulmonary bypass.

The etiology and incidence of neurologic injury occurring after cardiac operations employing cardiopulmonary bypass is reviewed. Results of studies demonstrating the role of microemboli generated by pump oxygenators, and evidence for the efficacy of arterial line filtration to decrease delivery of emboli into the cerebral circulation and to decrease postoperative neuropsychological dysfunction, are similarly reviewed. The impact of different strategies for management of pH during moderate hypothermic cardiopulmonary bypass on cerebral blood flow and coupling of cerebral flow and metabolism, as well as their impact on the incidence of postoperative cognitive dysfunction, are also discussed, along with the results of studies examining the efficacy of various agents including thiopental, nimodipine, and nafamostat to decrease cognitive dysfunction subsequent to bypass.

Anesthetics↗

Differential cortical atrophy in subgroups of mild cognitive impairment.

OBJECTIVE: To compare gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment (MCI) (those with a focal amnestic disorder and those with more diffuse cognitive dysfunction) with those of elderly controls. DESIGN: Magnetic resonance imaging volumetric study of MCI subgroups (MCI-amnestic [MCI-A], and MCI-multiple cognitive domain [MCI-MCD]) using a whole brain voxel-based analysis. SETTING: Referral dementia clinic. Patients Thirty-seven patients with MCI (age range, 49-85 years; MCI-A, n = 9; MCI-MCD, n = 28) and 47 control subjects (age range, 55-81 years). MAIN OUTCOME MEASURES: Volumetric anatomical magnetic resonance imaging differences between MCI subgroups and normal controls, and between patients with MCI who progressed to dementia. Magnetic resonance imaging scans were analyzed using statistical software SPM99. RESULTS: Overall, the patients with MCI had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, compared with control subjects. Compared with patients with MCI-MCD, patients with MCI-A had significant volume loss of the left entorhinal cortex and inferior parietal lobe. Compared with patients with MCI-A, patients with MCI-MCD had significantly reduced volume of the right inferior frontal gyrus, right middle temporal gyrus, and bilateral superior temporal gyrus. Patients with MCI who progressed to Alzheimer disease during follow-up (mean interval 2 years, maximum 4.5 years), showed greater atrophy in the left entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did not progress. CONCLUSIONS: These data provide evidence of distinct brain structural abnormalities in 2 groups of patients with MCI. While both have mesial temporal and cortical volume loss, those with a focal memory deficit have more involvement of the mesial temporal structures and less involvement of the neocortical heteromodal association areas than those patients with MCI with diffuse cognitive dysfunction. Thus, MCI may represent a more heterogeneous group than currently conceived, possibly reflecting 2 different etiological processes to dementia. These data also suggest that these structural abnormalities precede the development of Alzheimer disease.

Aged↗

Nicotinic receptor subtypes and cognitive function.

Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine-induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either alpha 4 beta 2 or alpha 7 antagonists. Ventral hippocampal alpha 4 beta 2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal alpha 7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, alpha 4 beta 2 and alpha 7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, alpha 7 antagonist cotreatment actually reversed the working memory impairment caused by alpha 4 beta 2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.

Amygdala↗

[Dementia--diagnosis and treatment in a geriatric memory clinic].

INTRODUCTION: Today it is certain that dementia is caused by a disease and not by ageing. The field is within the neurological, psychiatric and geriatric subject areas. In the city of Copenhagen, discovery and treatment of dementia occur on three levels: (1) in general practice, (2) in local memory clinics headed by specialists in geriatrics, neurology and/or psychiatry, and (3) in the memory clinic at H:S Rigshospitalet. In 2000, the geriatric clinic at H:S Bispebjerg Hospital established a local memory clinic. The fact that the clinic was created within a basic speciality other than neurology, as at Rigshospitalet, made it necessary to carry out developmental work. MATERIALS AND METHODS: A descriptive evaluation of 450 consecutive patient courses was performed. The patients were evaluated and treated in the memory unit in the period from 14 March 2001 to 31 December 2004. RESULTS: 330 (73%) of the 450 patients were women, and 120 (27%) were men. The median age was 84 years (range 64-97 years), and the median MMSE score was 24 (range 1-30) at first consultation in the memory unit. A cerebral CT was done on 339 patients (75%), and a SPECT scan was done on 6 patients (1%). 90 patients (20%) were evaluated by a gerontopsychiatrist during the treatment course, and 151 patients (34%) were evaluated by a neuropsychologist. A diagnosis of irreversible dementia was made for 322 patients (72%). CONCLUSION: Most of the patients referred had a MMSE score greater than 20, and even patients with very high MMSE scores may suffer from irreversible dementia. Compared with examinations in Danish memory clinics in the context of neurology, there was a higher number of patients with irreversible dementia. The difference may probably be explained by the average age difference between the patients referred. The threshold of referring for evaluation of cognitive dysfunction may be lower for younger patients than for older patients. The geriatric concept is an appropriate platform for evaluation and treatment of older patients with cognitive dysfunction before such patients are hospitalized on an emergency basis or break down socially. To carry out complete and qualified evaluation and treatment, it is essential to establish local and close cooperation with a gerontopsychiatrist, a neurologist and a neuropsychologist.

Aged↗

Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up.

OBJECTIVES: To assess the evolution of cognitive dysfunction in early-onset multiple sclerosis, to identify clinical predictors of mental decline, and to determine its impact on a patient's everyday life. DESIGN: The cognitive performance of 50 patients with multiple sclerosis on a neuropsychological battery was compared with that of 70 control subjects initially and again after a 4-year interval. Clinical predictors of cognitive impairment and its effect on daily life were analyzed by stepwise linear regression. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: A consecutive sample of 50 inpatients and outpatients with multiple sclerosis (mean disease duration, 1.58 years) and 70 demographically matched healthy control subjects selected from the patients' relatives and friends. MAIN OUTCOME MEASURES: Mean psychometric test scores of both groups at the initial and follow-up testing. Regression coefficients measuring the relationship between clinical parameters and cognitive capacity and between mental decline and performance of common tasks measured by the Environmental and the Incapacity Status scales. RESULTS: Multiple sclerosis-related deficits in verbal memory and abstract reasoning on initial testing remained more or less stable on the retest, at which time linguistic disturbances on the Set and Token tests also emerged. A patient's initial disability level predicted decreased performance on only four of 13 cognitive variables, and disease duration did so on only two. Extent of intellectual decline on initial testing, initial disability level, and progressive course were independent determinants of handicap in a patient's work and social activities. CONCLUSIONS: Cognitive and neurological deficits appear not to develop in parallel. Yet cognitive dysfunction proves to be a predictor of handicap in everyday life, even in patients in the incipient phase of multiple sclerosis.

Adolescent↗

Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

OBJECTIVE: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. METHOD: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. RESULTS: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. CONCLUSIONS: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.

Adult↗

Brain lesions on MRI in elderly patients with type 2 diabetes mellitus.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) type 2 has been associated with poor cognitive performance and dementia, particularly in elderly patients. The exact mechanisms underlying the cognitive dysfunction in DM remain unclear. Imaging studies of the brain could be helpful to give more insight into possible structural brain lesions underlying these cognitive dysfunctions. Therefore, we performed a study in independently living patients with DM type 2 in order to investigate the association between DM and brain imaging abnormalities. METHODS: The study population consisted of 45 patients with DM type 2 without hypertension (mean age 73.4 +/- 5.1 years, mean duration 16.5 +/- 11.5 years), 45 patients with DM type 2 and hypertension (mean age 73.5 +/- 6.1 years, mean duration 11.9 +/- 9.2 years) and 44 control subjects (mean age 73.1 +/- 5.4 years). All patients and control subjects underwent an MRI of the brain. White matter lesions (WML), cerebral atrophy and medial temporal lobe atrophy were rated by a standardized visual rating scale. Lacunar infarcts were defined as focal hypo-intensities on fluid-attenuated inversion recovery sequences with a hyperintense rim around it. RESULTS: WML occurred more frequently in diabetic patients with hypertension as well as without hypertension. Significantly more deep WML were found in DM patients with and without hypertension when compared to control subjects, whereas no difference was found in the occurrence of periventricular hyperintensities. In all 3 groups, lacunar infarcts occurred sporadically. A trend towards higher atrophy scores was seen in patients with DM compared to control subjects. CONCLUSIONS: The data of this cross-sectional study suggest that type 2 DM is an independent risk factor for deep WML in the independently living elderly patients.

Aged↗

Use of hyperbaric oxygen in rheumatic diseases: case report and critical analysis.

Hyperbaric oxygen has been used in patients with rheumatic disease for many years without reports of untoward or unusual complications for a variety of non-rheumatic indications. Recent evidence that hyperbaric oxygen inhibits the actions of certain cytokines, acts as an immune modulator and may help cognitive dysfunction has resulted in a re-examination of its potential role in rheumatic diseases. A case report of a lupus/scleroderma crossover patient is presented whose cognitive dysfunction improved after hyperbaric oxygen therapy. The history of hyperbaric oxygen and its physiology are related, along with a focused review of its effects on the immune and central nervous systems. Areas which might warrant further consideration by rheumatologists are outlined, as well as areas of concern.

Cognition Disorders↗

Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly.

The sensitivity of MRI volumetric measures to detect cognitive dysfunction is examined in 39 participants of an epidemiological field study (age 75-85, MMSE 19-30). According to Clinical dementia rating (CDR), 17 subjects had normal cognition (CDR 0), 12 had questionable (CDR 0.5) and 10 mild dementia (CDR 1). Discriminant analysis based on four hippocampal measures resulted in a correct classification of 76.9% of all subjects. Left-sided and posterior hippocampal measures were more responsible for group discrimination than right-sided and anterior measures. In CDR 0.5, a significant hippocampal volume reduction of 14.3% vs.11.3% (left vs. right) relative to normal was found. The right hippocampus was significantly greater than the left in CDR 0 and CDR 0.5, but not in CDR 1. The magnitude of non-directional hippocampal asymmetry increased with decreasing cognitive state. We conclude that hippocampal atrophy is sensitive to detect cognitive dysfunction and subjects at risk for Alzheimer's disease in the elderly population.

Aged↗