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Results for “Cognitive Dysfunction”

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PubMed1983

Reliability and validity of the Rational Behavior Inventory with a clinical population.

Administered to mental health outpatients (N = 75) who were receiving Psychotherapy the Rational Behavior Inventory as well as several other scales of psychological adjustment prior to their first therapy session. Their therapists also completed several of these scales on their clients. This procedure was repeated for a subsample upon termination of treatment. Correlations were computed among measures, and t-tests were conducted between pre- and posttreatment scores. Significant correlations were found between all measures in the expected directions, and significant pre- to post-scale differences were identified consistent with the expected effects of treatment. These results are interpreted as initial evidence for the Rational Behavior Inventory's reliability and validity with a clinical group. Future research is suggested to examine the Rational Behavior Inventory's relationship to other measures of cognitive dysfunction.

Adaptation, Psychological↗

PubMedDate not supplied

CREB and the discovery of cognitive enhancers.

In the past few years, a series of molecular-genetic, biochemical, cellular and behavioral studies in fruit flies, sea slugs and mice have confirmed a long-standing notion that long-term memory formation depends on the synthesis of new proteins. Experiments focused on the cAMP-responsive transcription factor, CREB, have established that neural activity-induced regulation of gene transcription promotes a synaptic growth process that strengthens the connections among active neurons. This process constitutes a physical basis for the engram--and CREB is a "molecular switch" to produce the engram. Helicon Therapeutics has been formed to identify drug compounds that enhance memory formation via augmentation of CREB biochemistry. Candidate compounds have been identified from a high throughput cell-based screen and are being evaluated in animal models of memory formation. A gene discovery program also seeks to identify new genes, which function downstream of CREB during memory formation, as a source for new drug discoveries in the future. Together, these drug and gene discovery efforts promise new class of pharmaceutical therapies for the treatment of various forms of cognitive dysfunction.

Animals↗

PubMed2006

Cortical demyelination in multiple sclerosis: a substrate for cognitive deficits?

Recent studies highlight cortical demyelinated lesions as a feature of multiple sclerosis (MS) pathology, which has received little attention so far. Here, we describe that cortical plaques are frequent and widespread, in particular in patients with primary or secondary progressive MS. Furthermore, we describe that certain cortical areas, such as the cingulated gyrus, the insular cortex and the temporobasal cortex, are more affected than others. These data indicate that cortical lesions have to be considered as an additional pathological substrate for cognitive dysfunction in MS patients.

Adult↗

PubMed2005

Severe cognitive impairment correlates with higher cerebrospinal fluid levels of lactate and pyruvate in a canine model of senile dementia.

Diagnosis of dementia of the Alzheimer's type depends on clinical criteria and exclusion of other disorders because, at this time, a validated biological marker, aside from histological brain examination, remains to be established. The canine counterpart of senile dementia of the Alzheimer type (ccSDAT) is considered a promising model for examining behavioral, cellular and molecular processes involved in early phases of human brain aging and Alzheimer disease (AD). In order to investigate the first events taking place in canine cognitive dysfunction, in this paper we established a new and rapid behavioral test that finely discriminates the degrees of cognitive impairment. Cerebrospinal fluid (CSF) analysis was performed to determine the relationship between each disease stage and modification of cerebral energy metabolism. Our results demonstrate a parallel increase of lactate, pyruvate and potassium concentrations in the severe cognitive deficit. These differences are discussed in view of the neuroprotective role presently given to lactate.

Aging↗

PubMed2004

Cognitive functioning in schizophrenia and bipolar disorder: comparison of performance on the Repeatable Battery for the Assessment of Neuropsychological Status.

Cognitive dysfunction is an important feature of schizophrenia and bipolar disorder. There is uncertainty about the relative magnitude of cognitive deficits in these disorders. We evaluated a total of 446 individuals: 229 with schizophrenia, 117 with bipolar disorder, and 100 controls without a history of psychiatric disorder. All participants were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a cognitive screening battery that evaluated immediate verbal memory, visuospatial/constructional abilities, attention, language, and delayed memory. A comparison of the three groups showed significant differences on the RBANS total score and all of the measured domains. In all of the comparisons, the schizophrenia group obtained the lowest scores, followed by the bipolar disorder group, and then the individuals without psychiatric disorder. In an analysis of covariance of RBANS total scores with the patient samples, the difference between schizophrenia and bipolar disorder remained significant after controlling for a range of demographic and clinical variables. Both schizophrenia and bipolar disorder are associated with significant cognitive impairments, but those in schizophrenia are more severe. Cognitive deficits may be an appropriate target of treatment interventions in these disorders.

Adult↗

PubMed2001

Cognitive effects of nicotine.

Nicotine and other nicotinic agonists have been found to improve performance on attention and memory tasks. Clinical studies using nicotine skin patches have demonstrated the efficacy of nicotine in treating cognitive impairments associated with Alzheimer's disease, schizophrenia, and attention-deficit/hyperactivity disorder. Experimental animal studies have demonstrated the persistence of nicotine-induced working memory improvement with chronic exposure, in addition to the efficacy of a variety of nicotinic agonists. Mechanistic studies have found that alpha7 and alpha4beta2 nicotinic receptors in the hippocampus are critical for nicotinic involvement in cognitive function. Clinical and experimental animal studies provide mutually supporting information for the development of novel nicotinic therapies for cognitive dysfunction.

Adult↗

PubMed2001

Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus.

Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures.

Animals↗

PubMed2003

Glucose effects on cognition in schizophrenia.

Clozapine has been shown to improve verbal declarative memory and other cognitive functions in chronic schizophrenia. This raises the possibility that additional adjunctive manipulations might improve memory further. In this study, we hypothesized that glucose, which improves memory in a variety of conditions, including schizophrenia, would improve memory more than saccharin in a group of patients stabilized on clozapine. Twelve outpatients with schizophrenia who received treatment with clozapine participated in a double-blind, counterbalanced, crossover study. Subjects received beverages containing either glucose or saccharin on one occasion, and then the other beverage about a week later. Fifteen minutes after ingesting the beverage, subjects received a brief battery of neuropsychological tests to assess verbal declarative memory, attention, and executive functions. Blood glucose levels were assessed at baseline, and at 15 and 50 min after beverage ingestion. The main findings were that retention of a list of words was improved in the glucose condition, while performance on a complex test of sustained vigilance declined after glucose ingestion. These findings provide evidence that glucose improves declarative memory in patients with schizophrenia who were treated with clozapine, and underscore the possibility of developing effective protocols to reduce cognitive dysfunctions in the disorder. They also highlight the need to explore the extent to which glucose modulates nonmemory cognitive functions such as attention, and to understand more generally how glucose availability and regulation influence cognition.

Adult↗

PubMed2003

Cognitive functioning in young and middle-aged unmedicated out-patients with major depression: testing the effort and cognitive speed hypotheses.

BACKGROUND: Cognitive deficits are common in major depressive disorder, but their nature is unclear. The effort hypothesis states that performance on effortful tasks is disproportionately impaired compared with the performance on automatic tasks. The cognitive speed hypothesis states that depression is characterized by cognitive slowness, which is a source of cognitive dysfunctioning. The present study investigated both theories in unmedicated adult depressive patients. It was also investigated whether the cognitive deficits can be attributed to more general physical illness-related factors or specifically to depressive disorder. METHOD: Thirty non-psychotic depressive out-patients were compared with 38 healthy control subjects and 25 patients with severe allergic rhinitis. The effects of group on more automatic and more effortful aspects of cognitive tasks measuring cognitive speed (Concept Shifting Task, Stroop Colour Word Test, Memory Scanning Test) and memory retrieval (Visual Verbal Learning Task, Verbal Fluency Test) were evaluated by MANCOVA. Age, sex, education and pre-morbid intelligence were treated as covariates. RESULTS: The depressive group had cognitive deficits in the automatic processing subtask of the Stroop, memory scanning and memory span. Performance on more effortful tasks was not impaired. CONCLUSIONS: Our results are more consistent with the cognitive speed hypothesis. Cognitive functioning in depressive disorder seems to be characterized by a reduced speed of information processing in automatic subtasks.

Adult↗

PubMed1999

Differential cognitive response to a mood challenge following successful cognitive therapy or pharmacotherapy for unipolar depression.

This study examined the nature of cognitive reactivity to mood changes in formerly depressed patients. Patients who recovered either through cognitive-behavior therapy (CBT; N = 25) or through pharmacotherapy (PT; N = 29) completed self-reported ratings of dysfunctional attitudes before and after a negative mood induction procedure. In response to similar levels of induced sad mood, PT patients showed a significant increase in dysfunctional cognitions compared with patients in the CBT group. To evaluate the effects of such cognitive reactivity on the subsequent course of depression, follow-up analyses reassessed 30 patients several years after initial testing. Results indicated that patients' reactions to the mood induction procedure were predictive of depressive relapse. These findings argue for differential effects of treatment on cognitive reactivity to mood induction and for the link between such reactivity and risk for later depressive relapse.

Adult↗

PubMed2003

Cognitive function in people with chronic illness: inflammatory bowel disease and irritable bowel syndrome.

Recent research has shown that people with chronic illnesses often experience cognitive deficits, such deficits may be specific to a particular type of illness, reflecting the disease process itself, or they may be deficits that are common across a number of chronic illnesses. Our study investigated whether people with an organic disease (Inflammatory Bowel Disease) show cognitive dysfunction relative to the control group and people with a functional illness (Irritable Bowel Syndrome), and if so, to elucidate the mechanisms by which such dysfunction occurs. A quasi-experimental design using three groups of participants provided scores on IQ, memory, and cognitive flexibility. Differences in absolute scores were slight. However, a noticeable interaction effect was found between group and IQ: The illness groups showed a deficit in verbal IQ relative to both their own performance IQ and to that of the control group's verbal IQ. This verbal deficit cannot be explained by depression, cognitive load, or medication.

Adult↗

PubMed2005

Lifelong endocrine fluctuations and related cognitive disorders.

The aim of this review is to examine the relationship between endocrine fluctuation and cognitive functioning. A plethora of in vitro and in vivo studies has demonstrated the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented post-menopausal women suggest a temporary positive effect (notably on verbal memory), and four recent meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomised controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Several methodological differences between observation studies and controlled trials with regard to patient group, type, timing and duration of HRT, cognitive measures and analyses, are discussed to explain these discrepancies. The association between hormonal serum level and cognitive functioning remains controversial suggesting high inter-individual vulnerability in risk. Moreover, research on the impact of endocrine functioning on cognition during the female reproductive cycle suggests life-long fluctuations in vulnerability. Etiological models taking into account the interaction of clinical, reproductive, and menstrual events throughout life may provide a more valid approach in understanding the effects of steroids on the brain and in determining sub-groups at heightened risk. Cognitive disorders in the elderly are more likely be related to cumulated lifelong exposure to steroids, rather than to a specific exposure to a given steroid. Multifactorial models based on an exhaustive view of all hormonal events throughout reproductive life together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.

Aging↗

PubMed1997

Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance.

OBJECTIVE: Attentional deficits are a prominent aspect of cognitive dysfunction in schizophrenia. The anterior cingulate gyrus is proposed to be an important component of frontal attentional control systems. Structural and functional abnormalities have been reported in this region in schizophrenia, but their relationship to attentional deficits is unknown. The authors investigated the function of the anterior cingulate gyrus and the related neural systems that are associated with selective attention in patients with schizophrenia. METHOD: While subjects performed multiple blocks of a single-trial Stroop task, [15O]H2O positron emission tomography scans were obtained. Fourteen patients with schizophrenia were compared with 15 normal subjects matched for age, gender, and parental education. RESULTS: The patients with schizophrenia responded at the same rate but made more errors in color naming during the color-incongruent condition. Consistent with the authors' hypothesis, patients with schizophrenia showed significantly less anterior cingulate gyrus activation while naming the color of color-incongruent stimuli. CONCLUSIONS: Patients with schizophrenia fail to activate the anterior cingulate gyrus during selective attention performance. This finding adds to the understanding of the functional significance of the structural and metabolic abnormalities in schizophrenia that have been previously reported in this region of the brain.

Adult↗

PubMed1993

The nootropic compound BMY-21502 improves spatial learning ability in brain injured rats.

Although long-lasting cognitive dysfunction often follows clinical traumatic brain injury (TBI), few pharmacologic regimens have been developed to treat post-traumatic cognitive deficits. We have previously shown that, in the rat, experimental lateral fluid-percussion (FP) brain injury induces a profound impairment in retrograde memory. In the present study, we characterized alterations in the ability of rats to learn a novel task following lateral FP brain injury and examined the potential modulatory effects of the nootropic cognitive enhancer BMY-21502 on post-injury learning. Male Sprague-Dawley rats were subjected to lateral (parasagittal) FP brain injury of moderate severity (2.4 atm) or sham surgery (no injury). On days 7 and 8 post-injury, animals were tested in a Morris water maze for their ability to learn to navigate to a submerged, invisible platform using external visual cues. BMY-21502 (10 mg/kg) or vehicle was administered 30 min prior to the first trial on both days. A highly significant (P < 0.001) impairment in post-injury learning was observed in vehicle-treated brain-injured animals compared with vehicle-treated sham animals. Injured animals treated with BMY-21502 at one week post-injury showed significantly (P < 0.05) improvement in post-injury learning ability compared to injured animals treated with vehicle. Paradoxically, in uninjured control animals BMY-21502 treatment appeared to worsen learning scores. The results of this study indicate that BMY-21502 may be useful for attenuating the dysfunction in learning ability that occurs following TBI.

Animals↗

PubMed1999

Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli.

Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such, addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.

Animals↗

PubMed2006

Diffuse beta-amyloid plaques and hyperphosphorylated tau are unrelated processes in aged dogs with behavioral deficits.

Single and double-labeling immunocytochemistry has been used to learn about the localization, distribution, and possible relationship between beta-amyloid protein (Abeta) deposition and tau hyperphosphorylation in the canine cerebral cortex with age. Behavioral impairment, as reported by the owners and tested in all dogs, correlated with increased Abeta burden in old dogs. Abeta plaques were diffuse and they were not accompanied by modifications in synaptic protein expression. Plaques were not associated with increased active mitogen activated protein kinase (MAPK/ERK-P) and p38 kinase (p38-P) expression, and tau hyperphosphorylation in neighboring cell processes. Yet tau hyperphosphorylation, as revealed with phospho-specific antibodies to tauThr181 and tauSer396, increased with age in individual neurons. Moreover, the subcellular pattern shifted from perinuclear localization to granular cytoplasmic and nuclear distribution with age. Our results in dog suggest that Abeta diffuse plaque formation and tau hyperphosphorylation are independent events, both occurring during the process of aging. Although increased cognitive dysfunction is associated with increased tau hyperphosphorylation, further investigation is needed to understand whether tau hyperphosphorylation is causative of cognitive impairment or an independent process related to aging.

Aging↗

PubMed2005

Neurocognitive functioning in patients undergoing coronary artery bypass graft surgery or percutaneous coronary intervention: evidence of impairment before intervention compared with normal controls.

BACKGROUND: Cognitive deficits have been reported to occur in a significant proportion of patients undergoing coronary artery bypass grafting (CABG), but the extent to which these deficits were preexistent or related to the natural history of cognitive decline in this patient population remains poorly defined. METHODS: After excluding patients with conditions known to cause brain dysfunction (eg, hepatic dysfunction, stroke), a group of patients referred for percutaneous coronary intervention (PCI) or CABG (n = 82) was compared with an age- and education-matched control group that did not have clinical evidence of coronary artery disease (n = 41). These subjects underwent a battery of neurocognitive and emotional testing. RESULTS: Test score means for 5 of 14 different measures were significantly greater (impaired) in cardiac compared with control group subjects. Of cardiac subjects, 20% demonstrated clinical impairment (test result > or = 1 SD worse than mean for normative standards) in 6 of 14 tests, compared with 10% of the controls. By clinical standards, 46% of cardiac subjects would be considered to be impaired (score 1 SD or more below the control group mean) on 3 or more neuropsychologic measures, compared with 29% of the controls. By this (control group mean) standard, cardiac subjects demonstrated impaired scores on 3.06 +/- 2.6 tests compared with impairment in 2.0 +/- 2.35 tests for the control group (p = 0.01). CONCLUSIONS: Even excluding patients at high risk for brain dysfunction, cognitive impairment is found in patients with coronary artery disease before interventional therapy. Baseline impairment must be considered when evaluating outcomes after intervention.

Aged↗

PubMed2004

AMPA receptor modulators as cognitive enhancers.

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors mediate fast excitatory transmission throughout the central nervous system. Positive modulation of these receptors can potentially enhance cognition by, firstly, offsetting losses of glutamatergic synapses; secondly, promoting synaptic plasticity; and thirdly, increasing the production of trophic factors. The advent of small molecules that selectively enhance AMPA receptors in the brain made it possible to test these hypotheses. Preclinical experiments indicate that the compounds accelerate the encoding of memory and have positive effects on models of cognitive dysfunction. Initial results with human subjects are also positive. AMPA receptor modulators thus represent an entirely new approach to cognitive enhancement and the treatment of diverse brain disorders.

Humans↗