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Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome.

BACKGROUND: The objective of the current study was to assess the correlations between cognitive function, fatigue, quality of life, and circulating cytokine levels in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: Fifty-four patients with AML/MDS were seen for pretreatment evaluation of their cognitive function and symptoms. Fifty percent of the sample was reevaluated 1 month later, when response to protocol chemotherapy was assessed. RESULTS: A significant proportion of patients had impaired cognitive function prior to the institution of chemotherapy. Sixty-five percent of patients also experienced significant fatigue. Levels of the circulating cytokines interleukin 1 (IL-1), IL-1 receptor antagonist (IL-1RA), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were elevated highly compared with normal controls. Higher IL-6 levels were associated with poorer executive function, whereas higher IL-8 levels were associated with better memory performance. IL-6, IL-1RA, and TNF-alpha levels were related to ratings of fatigue. Fatigue and cognitive dysfunction were unrelated. Hemoglobin levels were not associated significantly with either cognitive dysfunction or fatigue. Patients who obtained a complete response tended to have better fine motor control at baseline and lower circulating IL-1 levels. Treatment did not have a significant impact on cognition, although fatigue levels tended to increase. CONCLUSIONS: Patients with AML/MDS are highly symptomatic and experience cognitive impairment and fatigue before the initiation of their treatment. The current results indicated a correlation between these symptoms and levels of circulating cytokines, providing some support to the hypothesis that cancer-related symptoms are related at least in part to cytokine-immunologic activation. Elucidation of immunologic correlates of symptoms will allow for targeted interventions.

Activities of Daily Living↗

Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat.

Repeated ingestion of phencyclidine by humans induces enduring schizophrenic symptomatology, particularly cognitive dysfunction. In the presently described series of experiments, the neurochemical and cognitive consequences of subchronic phencyclidine administration in the rat were explored. Repeated phencyclidine exposure led to a selective reduction in basal and stress-evoked dopamine utilization in the prefrontal cortex. In addition, rats previously subchronically-treated with phencyclidine were impaired on performance of a spatial working memory task in a delay-dependent manner. Importantly, these dopaminergic and cognitive deficits were observed after withdrawal from phencyclidine, and as such, the neurochemical and behavioral effects were due to drug-induced neurobiological changes rather than direct drug effects. These biochemical and behavioral data show that repeated phencyclidine administration induces prefrontal cortical cognitive deficits in rats, as in humans, and offer a biochemical perspective of the neural substrate underlying this cognitive impairment: inhibition of mesocortical dopamine neurons. Thus, these data may have relevance to psychiatric disorders involving prefrontal cortical dopaminergic hypoactivity and cognitive dysfunction, as has been hypothesized in schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗

A multimodal approach to managing the symptoms of multiple sclerosis.

Multiple sclerosis (MS) is a disease of the CNS with a challenging clinical course characterized by heterogeneous symptoms related to inflammation and demyelination. Disease-modifying agents (DMAs) are used to treat the related neuronal degradation. Certain symptoms occur regularly, although with variable frequency, regardless of treatment with DMAs. Because there is no cure for MS at this time, symptom management is critically important to quality of life. Symptoms commonly seen are spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction. Other symptoms include depression, bowel dysfunction, paroxysmal symptoms, and weakness. The symptom management model that provides optimal results for patients with MS is a multimodal approach using effective communication, patient education, physical modalities and activities, occupational and other therapies, and pharmacologic interventions. Individualizing treatment for each patient involves gaining control of symptoms as early as possible to prevent cycles of symptoms from developing.

Cognition Disorders↗

Lack of correlation between plaque burden and cognition in the aged monkey.

To assess whether amyloid plaque accumulation in the monkey brain can account for age-related cognitive impairment that begins at about 20 years of age, we measured plaque content in the brains of 14 rhesus monkeys aged 5-30 years. We used immunohistochemistry employing the monoclonal antibody 6E10, which is specific to amino acids 1-17 of the amyloid beta peptide to identify amyloid plaques in serial coronal sections of the forebrain. Amyloid plaques accumulate with age, starting at 25 years of age and escalating after 30 years. Until the age of 30, plaques are only found in a few monkeys and are relatively sparse. Results from our group and others show that plaque content and the proportion of individuals afflicted with amyloid plaques increase with age. Although both cognitive dysfunction and plaque content increase with age, amyloid plaque content does not correlate with the cognitive dysfunction observed in elderly monkeys since even in very old subjects some cognitively impaired animals have few amyloid plaques and others with abundant plaques show only minor cognitive impairments. In summary, amyloid plaques appear to accumulate significantly only in monkeys over 25 years of age but do not appear to be a causal factor in age-related cognitive decline of the normal aging rhesus monkey.

Aging↗

Non-cardiac comorbidities in chronic heart failure.

Non-cardiac comorbidity complicates heart failure care and is prevalent in one form or another for the majority of elderly patients with heart failure. This wide range of comorbidities, which includes respiratory comorbidities, renal dysfunction, anaemia, arthritis, cognitive dysfunction and depression, contributes to the progression of the disease and may alter the response to treatment. Polypharmacy is inevitable in these patients. Cardiologists and other physicians caring for patients with chronic heart failure (CHF) need to be vigilant to comorbid conditions that may complicate the care of these patients. Future trials should focus on optimal strategies for the comprehensive management of the elderly patients with CHF with multiple comorbidities rather than the isolated effects of single drugs in younger patients with few or no comorbidities.

Aged↗

The three cognitive examinations.

Cognitive dysfunction is a core feature of neuropsychiatric illness. We offer a framework or conceptualizing cognitive function and discuss bedside examination and neuropsychological assessment, as well as the limitations of these tools. We stress the clinical importance of executive cognitive dysfunction, and we provide guidance or its assessment.

Cognition↗

Cognitive function in amyotrophic lateral sclerosis.

Cognitive function in patients with amyotrophic lateral sclerosis (ALS) has drawn recent attention. However, the pathogenesis of cognitive dysfunction in patients with ALS remains uncertain. To explore the underlying mechanism for cognitive dysfunction further, we studied 26 patients with ALS (15 male and 11 female; age from 36 to 67 years) by using neuropsychological batteries, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). We also evaluated these patients and an additional 26 age- and sex-matched normal controls using neuropsychological batteries with special attention to the frontal lobe function. On the basis of neuropsychological examination, we classified patients into three groups using cluster analysis. Age, education level and severity were comparable across these subgroups. Neuropathologic examination was subsequently carried out in six patients. Patients in Group 1 and 2 had low scores on all measures compared to patients in Group 3 and normal controls. Patients in Group 1 and 2 had frontal atrophy on MRI and reduced isotope uptake in the frontal region on SPECT, which was more evident in patients in Group 1. On neuropathologic examination, patients in Group 1 showed spongy degeneration and neuronal loss in the frontal lobe. Patients in Group 3 showed no notable pathology in the frontal region. The gradient distribution of the scores for attention and executive function, as well as SPECT findings suggested the presence of a continuum of cognitive disability in patients with ALS corresponding to the pathologic process in the frontal lobe ranging from significant impairment to normality. We, therefore, believe that inattention and executive dysfunction alternatives may evolve in patients with ALS corresponding to the pathologic process in the frontal lobe.

Adult↗

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

BACKGROUND AND PURPOSE: The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. METHODS: After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. RESULTS: Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. CONCLUSIONS: Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Age Distribution↗

Pure post-stroke cerebellar cognitive affective syndrome: a case report.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The 'cerebellar cognitive affective syndrome' is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event-related potentials showed abnormal P300. These data suggest a pure "cerebellar cognitive affective syndrome"and strengthen the hypothesis of cerebellar cognitive function modulation.

Aged↗

Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats.

Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss.

Animals↗

Evaluation of a lifestyle change programme for the treatment of obesity in general practice.

In order to evaluate the effectiveness of a cognitive behavioural group therapy programme for the treatment of obesity in clinical practice, 122 patients from 14 general practices (n = 70) were randomised into either a treatment or a control arm with a ratio of 3 to 2. The group treatment programme was also assessed in a clinical centre (n = 52; University Hospital Basel). Before therapy, a clinical interview and a mental disorder examination were carried out on all patients. The instructors of the programme (practitioners; clinic physicians) were trained during two afternoon meetings to supervise the group sessions. The treatment programme consisted of 16 group sessions of 90 min each, and contained psycho-educational elements concerning a balanced diet, instruction for the integration of more activity in everyday life (lifestyle activity), problemsolving strategies, and the cognitive restructuring of dysfunctional cognition regarding the own body. All the patients who were treated in the various settings demonstrated a benefit from therapy. Compared to the control groups which received usual medical care, they were able to reduce their starting weight by around 5% (p <0.001 for the group treated by practitioners) at the end of treatment and stabilise it until follow up after one year. In regard to psychological factors the treatment groups showed an increased sense of control over eating behaviour, and feelings of distractibility and hunger were reduced after treatment and at follow up (p <0.05). All treatment groups showed statistically relevant increases in feelings of attractiveness regarding their body and shape (p <0.05). These results support the effectiveness of the integrated cognitive behavioural treatment programme in clinical practice over a duration of 12 months.

Adult↗

Cognitive functions in prepsychotic patients.

OBJECTIVE: Cognitive dysfunctions are now widely understood as an essential feature of schizophrenia. A great number of cognitive disturbances have been described in drug-naive first-episode patients as well. The full-blown psychotic symptoms are usually preceded by a longer prodromal period, in which non-specific psychological disturbances are already present. The late prodromal phase is also coined as the prepsychotic state, with attenuated, isolated psychotic symptoms. The aim of the present study was to detect cognitive dysfunctions among young adults at the prepsychotic stage with the use of a standardized computer based cognitive test battery. METHOD: Eleven (9 men, 2 women) young Hungarian adults referred to the Outpatient Clinic of the Department of Psychiatry at the University of Debrecen were studied. The patients were re-evaluated for psychotic symptoms after 12 months. The patients had no history of psychiatric disorders or psychotic episodes and were referred by general practitioners on account of non-specific emotional or behavioural abnormalities. The subjects were asked to perform a series of 13 computerized neuropsychological tests of the Cambridge Neuropsychological Test. The performance of the patients were compared to that of the standardized database of the Cambridge Neuropsychological Test. RESULTS AND DISCUSSION: The performance of the prepsychotic patients was significantly lower compared to the healthy individuals in the paired associate learning (PAL, p<0.001), Spatial recognition memory (SRM, p<0.05), Rapid visual processing (RVP, p<0.05), and Spatial working memory (SWM, p<0.05) tests. CONCLUSION: Cognitive deficits were found mainly in attentional, frontal and prefrontal cognitive functions. These impairments may be present at the early stages of the development of psychosis and the standardized cognitive test battery (CANTAB) might be a useful tool for the detection of early cognitive impairments and provide a rationale for early intervention in individuals at risk of developing psychosis.

Adult↗

Type-2 diabetes and cognitive function in a non-demented population.

OBJECTIVES: To study if type-2 (non-insulin-dependent) diabetes mellitus (NIDDM) is associated with cognitive dysfunction independently of clinically diagnosed dementia in an elderly population. MATERIAL AND METHODS: Cognitive function was investigated with a brief neuropsychological test battery in a non-demented elderly population consisting of 183 NIDDM (World Health Organization, 1985) patients and 732 non-diabetic subjects. RESULTS: Patients with NIDDM were impaired in the Trail-Making Test parts A and C, which may be a reflection of mildly affected frontal lobe/executive functions. Women with NIDDM performed better than non-diabetic subjects in the Mini-Mental State Examination. CONCLUSIONS: We conclude that NIDDM per se is not associated with impaired memory in the elderly, and the minor defects observed in tests of frontal lobe/executive functions are unlikely to affect daily living. In the non-demented population aged 69 78 years, NIDDM does not carry a significant risk of cognitive dysfunction, when compared to the non-diabetic subjects.

Activities of Daily Living↗

Management of behavioral and psychiatric problems in Parkinson's disease.

Behavioral and psychiatric problems associated with idiopathic Parkinson's disease (PD) include cognitive dysfunction, drug-related psychosis, depression, anxiety, apathy, fatigue and sleep disturbance. These nonmotor symptoms are a significant cause of disability at all stages of illness. Cognitive dysfunction spans a continuum from circumscribed cognitive impairments to severe global dementia which can occur in up to 10-30% of advanced PD patients. Psychosis develops in 20-30% of PD patients receiving chronic antiparkinsonian therapy. Visual hallucinations and paranoid delusions are the most frequent symptoms. The gradual elimination of drugs of lesser priority that may affect cognition and/or cloud the sensorium constitutes the first step in the management of cognitive and psychotic symptoms. Atypical neuroleptic agents are an invaluable tool in those cases in which maximum drug regimen simplification is not adequate or results in unacceptable immobility. Depression and anxiety often go unrecognized although they are eminently treatable and may be important contributors to the morbidity of PD. They are present in 30-40% of PD patients and frequently occur together in association with other nonmotor symptoms such as apathy, fatigue and sleep disturbance. A combination of early recognition, counseling, antidepressant therapy, antianxiety and well-balanced antiparkinsonian therapy sets the stage for improved quality of life for patients with PD.

Journal Article↗

Memory dysfunction in myasthenia gravis: evidence for central cholinergic effects.

Two studies are presented that investigate the possible central cholinergic effects of myasthenia gravis as measured by cognitive dysfunction. In the first study, performance on a battery of cognitive tasks by 12 subjects with myasthenia gravis is compared with that of ten healthy control subjects and ten medical control subjects with chronic disease of a nonneurologic nature. The tests used were the Boston Naming Test, Rey Auditory Verbal Learning Test (AVLT), and the Logical Memory and Design Reproduction portions of the Wechsler Memory Scale (WMS). Results indicate that the myasthenic group was significantly impaired relative to both the medical and healthy control groups for performance on the Boston Naming Test, WMS Logical Memory, and WMS Design Reproduction. Both the myasthenic and the medical control groups were impaired relative to the healthy controls on the AVLT. In the second study, a myasthenic patient had plasmapheresis for treatment of her myasthenia on two separate occasions. Her memory was examined prior to as well as following each series of plasma exchanges with a variation of the Peterson-Peterson consonant trigram task. Results showed that this patient had significantly fewer interference effects and less rapid forgetting following plasmapheresis. The results of these two studies support the hypothesis that myasthenia gravis has central cholinergic effects manifested by cognitive dysfunction.

Adult↗

Cognitive executive dysfunction in patients with obstructive sleep apnea syndrome (OSAS) after CPAP treatment.

We have previously described impairments of cognitive executive functions in 17 patients with OSAS in comparison with 17 normal controls, as assessed by various frontal-lobe-related tests. In the present study, 10 of these OSAS patients treated with continuous positive airway pressure (CPAP) were reevaluated after 4-6 months of treatment. Neuropsychological tasks explored attention, short-term memory span, learning abilities, planning capacities, categorizing activities, and verbal fluency. Patients were found to have normalized most of their cognitive executive and learning disabilities, but all the short-term memory tests remained unchanged. These findings are discussed in light of the contribution of the frontal-lobe-related systems to short-term memory functions, and the eventual pathogenic role played by sleep fragmentation and nocturnal hypoxemia, which are related to the occurrence of apneic and hypopneic events. In conclusion, short-term memory impairment was persistent in OSAS patients despite CPAP treatment for 4-6 months.

Adult↗

Memory function in patients with stable, moderate to severe cardiac failure.

BACKGROUND: Psychologic dysfunction is common in patients with heart disease. Patients with end-stage cardiac failure have cognitive dysfunction that can affect their ability to comply with complex treatment regimes. The prevalence of cognitive dysfunction in patients with stable, moderately severe cardiac failure is not known. The purpose of this study was to evaluate the prevalence of memory dysfunction in that population. METHODS: Twenty patients with previous myocardial infarction (MI), New York Heart Association class III or IV cardiac failure symptoms, and left ventricular ejection fraction (LVEF) <40% were studied. Twenty patients with previous MI, no heart failure symptoms, and LVEF >50% were studied as a control group. Memory function was assessed with the Rivermead Behavioural Memory Test and digit span test. Results were controlled for affective state and estimated premorbid intellectual function with the National Adult Reading Test. RESULTS: Patients with cardiac failure performed as well as controls in the memory test (mean [95% confidence intervals] score 18.2 [16.5-19.9] versus 19.7 [18.1-21.4] points, P =.20) and digit span test (10.1 [9.2-11.0] versus 11.0 [9.9-12.2] points). Affective symptoms were more prevalent among patients with cardiac failure. Estimated premorbid intellectual function appeared poorer in patients with cardiac failure (reading test score 24 [7-36] versus 32 [11-46] points). Memory test outcomes were not significantly affected after adjustment for these variables. CONCLUSIONS: Patients with prior MI and stable, moderately severe cardiac failure do not have significantly memory impairment. Memory dysfunction is not likely to interfere with rehabilitation or compliance with treatment regimes. Anxiety and depression, however, are relatively common in this group.

Aged↗

Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia.

BACKGROUND: Cognitive deficits are a characteristic feature of schizophrenia and contribute to the profound disabilities associated with this illness. Some of the cognitive deficits that occur in individuals with schizophrenia are similar to those found in individuals who have recovered from central nervous system infections with human herpesviruses. METHODS: We measured cognitive functioning and serologic evidence of infection with human herpesviruses in 229 outpatients with schizophrenia. We evaluated cognitive functioning with the Repeatable Battery for the Assessment of Neuropsychological Status. For each patient, serum IgG class antibodies with specificities for the following potentially neurotropic human herpesviruses were measured by means of a solid-phase immunoassay: herpes simplex viruses 1 and 2, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and varicella-zoster virus. We determined the association between serologic evidence of herpesviruses infection and cognitive functioning by univariate and multivariate analyses, including demographic and clinical factors associated with cognitive functioning. RESULTS: We found that serologic evidence of infection with herpes simplex virus 1 is an independent predictor of cognitive dysfunction in individuals with schizophrenia. Discriminant function analysis indicated that much of the difference in cognitive functioning could be attributed to immediate memory. We found no significant association between cognitive dysfunction and serologic evidence of infection with other human herpesviruses. CONCLUSION: Serologic evidence of herpes simplex virus 1 infection is associated with cognitive impairment in schizophrenia.

Adolescent↗