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PubMed2005

Cognitive, emotional, physical and social effects of growth hormone treatment in adults with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of improvements with GH replacement. We have studied cognitive, emotional, physical and social parameters in PWS adults at baseline, during and after GH treatment. PATIENTS AND METHODS: Nineteen patients, 9 females and 10 males, median age 25 years, mean BMI 35 kg/m2 participated in this study. Approximately half of the group had GHD. All patients fulfilled the clinical criteria for PWS and 13 had a positive genotype. The patients were randomized to 6 months of treatment with either GH [1.6 IU/day (0.53 mg/day)] or placebo, followed by 12 months of active GH treatment. Treatment was then stopped, and the patients were followed for an additional period of 6 months. A test battery for general cognitive evaluation and a computer-based measurement of reaction time, motor speed and fluency were employed at baseline, after 6 months and at the end of GH treatment. At the same time intervals, a self-evaluation questionnaire was answered at the end of each test session. Other questionnaires reflecting the patients' cognitive, emotional, physical and social status were answered by relatives/caretakers at baseline and at 3 and 6 months following cessation of GH treatment. RESULTS: Baseline cognitive level was estimated to be moderately to mildly impaired; IQ range was 40-90. The results from some of the cognitive and the motor performance tests improved significantly after 6 and 18 months of GH treatment. According to the questionnaires, both the patients and the relatives/caretakers evaluated physical status rather negatively at baseline, but still, impairments in both physical and social status and overall functioning were observed when GH treatment was discontinued. The self-evaluation did not change in any aspect during GH treatment. CONCLUSIONS: In this pilot study of an adult PWS cohort, we were able to document beneficial effects in mental speed and flexibility and in motor performance during GH treatment. Impairment was seen in physical and social status as well as overall functioning, when GH treatment stopped. Studies of larger cohorts are needed to further elucidate the role of GH treatment in this group of patients.

Adult↗

PubMedDate not supplied

Quantitative EEG correlates of cognitive deterioration in the elderly.

We report on the quantitative analysis of the EEG (QEEG), using the Neurometric method, in large samples of normal elderly; normal subjectively impaired elderly; patients with mild cognitive impairment; patients presenting with a continuum of primary cognitive deterioration from mild to moderately severe as measured by the Global Deterioration Scale (GDS), compatible with dementia of the Alzheimer's type (DAT). Neurometric QEEG measures were found to be a sensitive index of degree of cognitive impairment, especially reflected in increased absolute and relative power in the theta band, with delta increasing in later stages of deterioration. While these abnormalities were widespread, neither localized or lateralized, MANOVA's for GDS and relative power in theta reached highest significance in a bilateral temporo-parietal arc. A possible relationship between hippocampal dysfunction, cognitive deterioration, and theta abnormalities is discussed in relation to these findings. The results suggest that Neurometric QEEG features are sensitive to the earliest presence of subjective cognitive dysfunction and might be useful in the initial evaluation of patients with suspected dementia, as well as in estimating the degree of cognitive deterioration in DAT patients.

Aged↗

PubMed2004

Nicotine improves antisaccade task performance without affecting prosaccades.

Although there is ample evidence for a cognitive-attentional benefit of the stimulant nicotine, the source of this benefit is not as well understood. One approach is to address what aspects of performance nicotine affects at a functional systems level. It is currently debated whether the benefits produced by nicotine are the effect of enhanced higher cognitive function or reflect an overall increase in general arousal. In order to address this question, the effects of nicotine on two simple eye movement tasks were studied: the saccade (S) and antisaccade (AS) tasks. Because the S and AS tasks utilize identical sensory stimuli (peripheral targets) and require identical motor responses (eye movements) but differ significantly in their cognitive demands, the use of these two tasks should enable a parsing of nicotine effects on cognitive versus sensory-motor processes. In this study, the S and AS tasks were performed by two experimental groups, task naïve subjects and highly practised subjects. For the first group, that of the task naïve subjects, nicotine gum administration resulted in a decrease in AS errors. For the second group, that of two experienced subjects tested repeatedly over a 3 week period, nicotine also produced a significant decrease in AS task errors, as well as resulting in a significant decrease in AS response times. Neither task naïve nor experienced subjects showed any effects of nicotine on the S task. Examining the effects of nicotine on highly controlled and constrained tasks such as the S and AS task may provide another level of insight into the mechanisms underlying the beneficial cognitive effects of nicotine.

Humans↗

PubMed1998

Association of elevated alpha 1-antichymotrypsin with cognitive impairment in a prospective study of the very old.

OBJECTIVE: The authors investigated the relationships between concentrations of two acute-phase proteins, alpha 1-antichymotrypsin (ACT) and alpha 2-macroglobulin (MAC), and cognitive impairment in the very old. METHOD: Concentrations of ACT and MAC were determined in a prospective study using sera from medically stable elderly nursing home residents. Cognitive impairment was assessed with the Mini-Mental State. RESULTS: Concentrations of ACT were associated with greater cognitive impairment, as reflected by lower Mini-Mental State scores. This relationship did not exist for MAC. CONCLUSIONS: These data extend previous reports that patients with Alzheimer's disease have greater concentrations of ACT in their blood by demonstrating in a diagnostically diverse nursing home population a relationship between serum ACT and mental status. Elevated serum ACT in patients with compromised mental status may reflect a cerebral acute-phase response.

Acute-Phase Proteins↗

PubMed2005

Hypertension and cognitive performance in African Americans with Alzheimer disease.

The authors examined the relationship between hypertension and cognitive performance in 34 African-American patients with probable Alzheimer disease. Multiple regression analyses indicated that hypertension was associated with poorer overall performance on the Mattis Dementia Rating Scale, particularly the Initiation/Perseveration and Conceptualization subscales, after controlling for gender, age, and education. The findings suggest that African-American patients with hypertension exhibit greater cognitive impairment, possibly reflecting executive dysfunction.

Black or African American↗

PubMed2006

Methicillin-resistant Staphylococcus aureus colonization is associated with higher mortality in nursing home residents with impaired cognitive status.

OBJECTIVES: To assess the effect of methicillin-resistant Staphylococcus aureus (MRSA) colonization on morbidity and mortality of nursing home residents. DESIGN: Three-year cohort study from 2000 to 2003. SETTING: Twenty-three nursing homes of all types and regions in the northern part of Belgium (Flanders). PARTICIPANTS: Two thousand eight hundred fourteen nursing home residents. MEASUREMENTS: The consequences of MRSA colonization on mortality and hospitalization were studied, adjusting for potential confounders. Dates and cause of death and hospitalization were collected every 6 months during 3 years of follow-up. RESULTS: After adjustment for age, sex, and Charlson comorbidity index, the risk for 36-month mortality remained significantly higher in MRSA carriers (hazard ratio (HR) = 1.4, 95% confidence interval (CI) = 1.1-1.8) than in noncarriers. The effect of MRSA on mortality was dependent on the degree of cognitive impairment, with the highest effect in patients with severe cognitive impairment (adjusted HR = 1.8, 95% CI = 1.1-2.8) and absence of effect in residents with good mental status (adjusted HR = 0.8, 95% CI = 0.43-1.62). Deaths were more frequently reported to be infection-related in MRSA carriers. No association was found between MRSA colonization and hospitalization for any reason, but during follow-up, MRSA carriers were twice as frequently hospitalized for respiratory tract infections. CONCLUSION: Colonization of MRSA in Belgian nursing home residents was associated with higher mortality. This excess mortality was restricted to residents with impaired cognitive function, probably reflecting differences in therapeutic approaches, in delay of diagnosis of pneumonia and other acute disorders in these patients, or in both.

Aged↗

PubMed2004

The impact of problem structure on planning: insights from the Tower of London task.

Despite the large number of behavioral and functional neuroimaging studies employing the Tower of London (ToL), the task's structural parameters and particularly their impact on planning have not been addressed so far. In this paper, we highlight the structural properties of ToL problems and provide evidence for their systematic and substantial effects on the cognitive processes involved in planning. In a problem set with three-move problems, the following structural parameters were experimentally manipulated: the ambiguity of goal hierarchy, the demand for subgoal generation, and the existence of suboptimal alternatives. Analysis of preplanning time as an indicator for the planning process revealed highly significant effects for all three parameters which seems to reflect differences in cognitive processing due to structural task properties. Therefore, we suggest that the common consideration of ToL problem difficulty solely in terms of the minimum number of moves is not sufficient. Moreover, the applied problem sets should be more carefully selected and their structural parameters explicitly noted.

Adult↗

PubMed2004

Activation of human medial prefrontal cortex during autonomic responses to hypoglycemia.

Studies in humans implicate the medial prefrontal cortex (MPFC) in complex cognitive and emotional states. We measured regional cerebral blood flow (CBF) four times each during euglycemia (5.2 +/- 0.2 mmol/liter) and hypoglycemia (3.0 +/- 0.3 mmol/liter) in nine normal human volunteers. Autonomic responses during hypoglycemia were manifested by increases in neurogenic symptoms, heart rate, and plasma levels of epinephrine, norepinephrine, and pancreatic polypeptide. Typical symptoms of hypoglycemia were mild, and none reflected evidence of cognitive or emotional stress. Quantitative CBF fell 6-8% in the cerebrum, brainstem, and cerebellum. Analysis of regional CBF differences identified neuronal activation during hypoglycemia in bilateral MPFC (areas 24 and 32) and bilateral thalamus. These results provide evidence that the MPFC participates in the autonomic responses to simple physiological stimuli in humans.

Adolescent↗

PubMed1986

Thought deficit in psychotic depression and chronic paranoid schizophrenia: methodological and conceptual issues. Commentary on Marjorie L. Carter's "The assessment of thought deficit in psychotic depression and chronic paranoid schizophrenia".

Based on test comparisons involving psychotic depressives and chronic paranoid schizophrenics, Carter (J. Nerv. Ment. Dis. 174: 336-341, 1986) inferred that cognitive disorder may reflect a general psychosis factor rather than a differential diagnostic marker. Review of the design and analysis raises methodological and conceptual issues that obviate such interpretation. Problems include absence of control for IQ and chronicity of illness, sample bias incurred by selectively matching groups for education, use of parametric statistics on ordinal data, measures that do not differentially assess cognitive deficit, plausible alternative explanations for nonsignificant outcome, and inadequate data base for generalizing about larger diagnostic groups or psychosis itself. Significant differences found by Carter and others suggest, instead, some fundamental distinctions in the nature if not extent of cognitive disorder in these two groups. It was proposed that a general psychosis factor may be a pervasive interfering variable that obscures diagnostic differences in cognition and thus needs to be rooted out by proper statistical or research design.

Chronic Disease↗

PubMed1994

An introduction to the psychophysiology of breathing.

Breathing can be viewed as an independent variable which affects emotion, cognition, and behavior as well as a dependent variable which reflects changes in emotion, cognition, and behavior. This bidirectional interaction is basic to an appreciation of the significance of breathing in terms of its relevance in research and application. The underlying premise of the present article is that since breathing is a behavior that is under voluntary as well as reflexive control, it can be modified according to the principles of both instrumental training (operant conditioning) and Pavlovian (classical) conditioning. The implications of this premise are relevant to theory, diagnosis, and treatment of stress and anxiety-related disorders (e.g., panic disorder, phobias, test anxiety, occupational strain, and related psychosomatic disorders), and to basic and applied research in the psychophysiology of breathing.

Humans↗

PubMed2004

Stereotype threat undermines intellectual performance by triggering a disruptive mental load.

Research on stereotype threat has repeatedly demonstrated that the intellectual performance of social groups is particularly sensitive to the situational context in which tests are usually administered. In the present experiment, an adaptation of the Raven Advanced Progressive Matrices Test was introduced as a measure of cognitive ability. Results showed that individuals targeted by a reputation of intellectual inferiority scored lower on the test than did other people. However, when the identical test was not presented as a measure of cognitive ability, the achievement gap between the target and the control group disappeared. Using heart rate variability indices to assess mental workload, our findings showed that the situational salience of a reputation of lower ability undermined intellectual performance by triggering a disruptive mental load. Our results indicate that group differences in cognitive ability scores can reflect different situational burdens and not necessarily actual differences in cognitive ability.

Adult↗

PubMed2006

Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice.

Intraneuronal alpha-synuclein (alphaSYN) inclusions constitute the hallmark lesions of a number of neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. In a transgenic mouse model expressing mutant [A30P]alphaSYN under control of the pan-neuronal Thy1 promoter, motor impairment became significant beyond 17 months of age. Cognitive performance was measured in the Morris water maze and upon fear conditioning. At 4 months of age, transgenic mice performed like controls. However, performance in these tasks was significantly impaired in (Thy1)-h[A30P]alphaSYN mice at 12 months of age. After completion of the cognition tests, mice were sacrificed and the regional distribution of neuropathology was examined. In contrast to 4 months old animals, 12 months old transgenic mice showed alpha-synucleinopathy in several brain regions, including the central nucleus of the amygdala, which is involved in cognitive behavior of mice, and is susceptible to alphaSYN pathology in human patients. Thus, age-dependent fibrillization of alphaSYN in specific cortical regions concomitant with cognitive decline may reflect dementia with Lewy bodies in a transgenic mouse model.

Age Factors↗

PubMed2000

The emotional modulation of cognitive processing: an fMRI study.

The functional neuroanatomy of visual processing of surface features of emotionally valenced pictorial stimuli was examined in normal human subjects using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two types: emotionally negative and neutral pictures. Task performance was slower for the negatively valenced than for the neutral pictures. Significant blood oxygen level dependent (BOLD) increases occurred in the medial and dorsolateral prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the posterior cortical visual areas for both stimulus types. Increases were greater for the negatively valenced stimuli. While there was a small but significant BOLD decrease in the subgenual prefrontal cortex, which was larger in response to the negatively valenced pictures, there was an almost complete absence of other decreases prominently seen during the performance of demanding cognitive tasks [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9, 648--663]. These results provide evidence that the emotional valence and arousing nature of stimuli used during the performance of an attention-demanding cognitive task are reflected in discernable, quantitative changes in the functional anatomy associated with task performance.

Adult↗

PubMed1991

Cognitive correlates of ventricular enlargement in vascular patients with leuko-araiosis.

We studied the cognitive significance of ventricular enlargement in 40 vascular patients with leuko-araiosis on MRI. We obtained significant differences between patients and normal controls without vascular risk-factors regarding ventricular measures. Ventricular size of the patients correlated with several neuropsychological tests measuring abstract reasoning, comprehension of language, constructional skills, speed and attention. These results suggest that ventricular enlargement in vascular patients reflects global deterioration of complex cognitive functions. Information proceeding from ventricular size is complementary to that coming from the degree of leuko-araiosis and probably has more clinical significance. Both leuko-araiosis and ventricular size may be neuroimaging parameters capable of reflecting the cognitive deterioration in vascular patients without large lesions.

Aged↗

PubMed2006

Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis.

In the acute phase of Graves' thyrotoxicosis patients often have subjective cognitive complaints. Continuing controversy exists about the nature of these symptoms and whether they persist after treatment. This prospective study included 31 consecutively referred, newly diagnosed, and untreated patients with Graves' thyrotoxicosis. A control group of 34 individuals matched for age, education and premorbid intelligence was also included. At baseline all patients and control subjects were examined with psychiatric rating scales and a comprehensive neuropsychological battery. The effect of treatment on affective symptomatology was examined in the patient group after reaching euthyroidism and 1 year after treatment initiation. At initial examination patients had significantly higher scores on psychiatric rating scales as compared with controls, and the majority reported memory and concentration problems. No significant differences between the patient and the control group on neuropsychological test performances were found. Thyroid levels did not correlate with the neuropsychological test performances or psychiatric ratings. After reaching euthyroidism the level of affective symptoms (including reports of cognitive deficits) had decreased significantly, with further normalisation 1-year after treatment initiation. In conclusion, patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis but comprehensive neuropsychological testing revealed no cognitive impairment. Reports of cognitive dysfunction may reflect affective and somatic manifestations of thyrotoxicosis and in most patients these symptoms disappear after treatment of Graves' thyrotoxicosis.

Acute Disease↗

PubMed1999

'Obsessions' in children with autism or Asperger syndrome. Content analysis in terms of core domains of cognition.

BACKGROUND: We report a survey of the content of obsessions in children with autism spectrum conditions. We use the term 'obsessions' narrowly, to indicate strong, repetitive interests. We predicted that obsessions would not cluster randomly, but rather would occur significantly more often in the domain of 'folk physics' (an interest in how things work), and significantly less often in the domain of 'folk psychology' (an interest in how people work). These predictions were tested relative to a control group of 33 children with Tourette syndrome. AIMS: To examine the content of autistic obsessions, and to test the theory that these reflect an evolved cognitive style of good folk physics alongside impaired folk psychology. METHOD: Ninety-two parents returned a questionnaire designed to determine the subject of their child's obsessional interests. The results were analysed in terms of core domains of cognition. RESULTS: Both predictions were confirmed. CONCLUSIONS: These results suggest that impaired folk psychology and superior folk physics are part of the cognitive phenotype of autism. A content-free theory of obsessions is inadequate.

Asperger Syndrome↗

PubMed1993

Information processing in children with minor neurological dysfunction: behavioural and neurophysiological indices.

Minor neurological dysfunction (MND) refers to deviant function of the central nervous system in the absence of localizable neurological disorders. Children with no signs (n = 28) and with varying grades of MND (n = 48), classified according to failure on circumscript neurological subsystems, were administered selective and sustained attention tasks at the age of twelve. During the execution of one of the tasks, electrocortical activity of the brain was recorded at the Fz, Cz, Pz and Oz scalp locations. Of main interest were behavioural and electrophysiological indices of deficits in attentional control. With respect to the latter category, the investigation was focused on differences in event-related potential amplitudes reflecting subprocesses of cognitive processing (processing negativity, P300). Following a linear stage model of information processing, it was found that children who failed on three or more neurological subsystems (in particular on fine manipulation and coordination), exhibited deficits in the encoding, search and decision stages of processing. Furthermore, the children with MND showed a reduced positive parietal shift on target presentation. Under complex task conditions, children without MND showed a decrease in P300 amplitude which reflects the impact of processing negativity as a result of increased task demands; this effect was absent in children with MND. These electrocortical differences suggest imbalances in the external and internal neural regulation of the flow of information in the brain.

Attention↗

PubMedDate not supplied

Role of neuropeptides in learning versus performance: focus on vasopressin.

Neuropeptides that have classical hormonal functions via the pituitary have been implicated in cognitive function. Systemically and centrally administered arginine vasopressin (AVP) has been well documented to prolong extinction and improve consolidation in avoidance tasks. However, major questions have centered on the physiological mechanism of action for these effects and whether these cognitive enhancing actions reflect learning or performance. Work with vasopressin antagonists has led to the hypothesis that the effects of systemically administered AVP may be mediated peripherally and may be secondary to increases in blood pressure and activating effects. Centrally administered AVP, however, can also facilitate memory and recent work using an olfactory social memory task suggests that these effects may be mediated, at least in part, by AVP systems in the lateral septum. These results suggest that the cognitive enhancing actions of AVP may involve two parallel, but ultimately homologous, systems at the functional level. Pituitary-derived AVP may facilitate memory actions through more nonspecific (performance) effects, whereas centrally derived AVP may facilitate memory actions through more direct effects on the neural substrates of memory processing in the limbic system.

Animals↗