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PubMed2006

Evaluation of cognition in cancer patients: special focus on the elderly.

PURPOSE: The risks of both cognitive dysfunction and most cancers increase with age. A literature review was undertaken to identify how cognitive issues in older patients were being assessed in the oncology literature. METHODS: A systematic literature search was undertaken using a number of different search terms and databases to find all relevant articles in oncology and internal medicine journals. RESULTS: Eighty-eight articles were included in the review. Just over half of the articles studied a mixture of cancer types and had fewer than 100 patients. The vast majority of patients being studied were <65 years of age. While a little over half of the articles used >or=3 neuropsychological tests to assess cognition, more than 60 different tests were used to assess cognition. Forty-one percent of the studies were prospective trials, with most of the rest divided between cross-sectional and observational. One-fifth of the articles involved patients at end-of-life. CONCLUSION: The oncology literature contains little information about cognition in older cancer patients. More systematic and comprehensive studies of this important aspect of cancer care in the elderly are necessary.

Aged↗

PubMed2000

The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys.

Stress exposure impairs the cognitive functioning of the prefrontal cortex (PFC). Previous research has examined the dopamine (DA) D1 receptor mechanisms underlying this response. The current study performed a preliminary examination of the role of D4 receptor mechanisms by determining whether the selective D4 receptor antagonist, PNU-101387G, could prevent stress-induced working memory deficits in monkeys. Animals were tested on the delayed response task following treatment with PNU-101387G (0 or 0.1-0.8 mg/kg, 60-min pretreatment), and the pharmacological stressor, FG7142 (0 or 0.2 mg/kg, 30-min pretreatment). FG7142 significantly impaired delayed response performance relative to vehicle; PNU-101387G pretreatment produced a dose-related reversal of the FG7142 response. PNU-101387G had no significant effects on its own, but there were trends toward improvement at low doses and impairment at higher doses. Further studies in a larger number of animals appear warranted. These preliminary findings suggest that D4 receptor mechanisms contribute to stress-induced cognitive dysfunction.

Animals↗

PubMed1995

Binding ties: closeness and conflict in adult children's caregiving relationships.

The authors used a path model to test the hypothesis that emotional closeness and conflict between adult-child caregivers (N = 90) and their impaired parents mediated the impact of the parents' functional and cognitive impairment on the caregivers' subjective stress, subjective effectiveness, and depression. Closeness mediated the relationship between cognitive impairment and both stress and effectiveness, whereas conflict mediated cognitive impairment for all 3 outcomes and generally accounted for more variance. There was limited evidence that functional impairment was mediated by the quality of the relationship. Results highlight the importance of both positive and negative ties as intervening mechanisms influencing caregivers' well-being, especially in the presence of cognitive dysfunction.

Adult↗

PubMed2005

Cognitive impairment associated with major depression following mild and moderate traumatic brain injury.

Traumatic brain injury (TBI) and major depression are neuropsychiatric conditions that have been associated with cognitive dysfunction. The aim of this study was to explore the relationship between major depression and cognitive impairment following mild and moderate TBI. Seventy-four TBI patients were assessed for the presence of major depression using the Structured Clinical Interview for the DSM-IV and completed a neurocognitive assessment battery. Subjects with major depression (28.4%), compared to those without, were found to have significantly lower scores on measures of working memory, processing speed, verbal memory and executive function. Potential mechanisms and implications for treatment are discussed.

Adolescent↗

PubMed2004

Reliable screening for neuropsychological impairment in multiple sclerosis.

In an earlier study, we developed the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) to assist in the screening for neuropsychological (NP) impairments. Self-report MSNQ scores correlated significantly with measures of depression, whereas informant-report MSNQ scores correlated with cognitive performance, but not depression. This study was criticized for use of a small sample and lack of data regarding normal performance and test-retest reliability. The present study was designed to replicate the earlier work with a larger sample of patients and normal controls obtained from multiple sites. We also evaluated the test-retest reliability and predictive validity of the MSNQ. The sample included 85 multiple sclerosis (MS) patients and 40 normal controls, matched on demographic variables. All participants completed the MSNQ and underwent NP testing. Thirty-four patients were re-examined at one week. Pearson and ANOVA techniques were utilized for univariate comparisons. Bayesian statistics were calculated to assess predictive validity. Patient self- and informant-report MSNQ scores differed from normal and test retest reliability indices were high. Both self- and informant-reports were correlated with cognitive dysfunction and depression scales. Self-report MSNQ scores correlated more strongly with depression than cognitive performance, whereas the opposite pattern was observed with informant-report scores. Bayesian statistics showed that informant-report MSNQ scores predict cognitive impairment and patient self-report scores identify patients with cognitive impairment or depression. It is concluded that the MSNQ is useful, although patient self-reports may be exaggerated in depressed patients or reduced in patients with severe cognitive impairment.

Adult↗

PubMed2005

Phosphodiesterase inhibitors for cognitive enhancement.

An effective treatment for age-related cognitive deficits remains an unmet medical need. Currently available drugs for the symptomatic treatment of Alzheimer's disease or other dementias have limited efficacy. This may be due to their action at only one of the many neurotransmitter systems involved in the complex mechanisms that underlie cognition. An alternative approach would be to target second messenger systems that are utilized by multiple neurotransmitters. Cyclic adenosine monophosphate (cAMP) is a second messenger that plays a key role in biochemical processes that regulate the cognitive process of memory consolidation. Prolongation of cAMP signals can be accomplished by inhibiting phosphodiesterases (PDEs). Eleven PDE families, comprised of more than 50 distinct members, are currently known. This review summarizes the evidence demonstrating that rolipram, a selective inhibitor of cAMP-selective PDE4 enzymes, has positive effects on learning and memory in animal models. These data provide support for the general approach of second messenger modulation as a potential therapy for cognitive dysfunction, and specifically suggest that PDE4 inhibitors may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases.

Animals↗

PubMed2026

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

PubMed1999

Vulnerability to emotionally negative stimuli in Parkinson's disease: an investigation using the Emotional Stroop task.

OBJECTIVE: The objective of this study was to determine whether the pathophysiological changes associated with Parkinson's disease (PD) lead to an increased vulnerability to react to negative emotional stimuli and hence to depression. It is hypothesized that nondepressed PD patients will demonstrate, associated with particular PD and/or cognitive variables, vulnerability to the interfering effects of negative words on the Emotional (sad) Stroop task (EST). BACKGROUND: Depression has been reported to occur frequently in PD, but there is controversy regarding its pathophysiology: psychosocial factors versus neurobiologic ones. METHOD: Thirty nondepressed/ nondemented patients with idiopathic PD attending a specialist movement disorders clinic were assessed from their emotional state (Beck's Depression Inventory [BDI], and Hospital Anxiety and Depression Scale) and from their cognitive state (Mini-Mental State Examination, Stroop tasks [including the EST], Modified Card Sorting Test, Word Fluency tasks, Digit Span, and Trail Making tests). In addition, information was gathered on PD-related variables such as severity (Hoehn and Yahr scale), duration of the disease, and type of motor response to dopaminergic drugs. The sample was split into two groups according to the median BDI score to allow for comparisons. One-way ANOVA techniques were used to look for significant differences between variables in the two groups. Bivariate correlations were used to look for significant relationships between variables in each group. RESULTS: The two groups only differed in parameters measuring emotional state. Only the subjects with higher BDI scores showed significant correlations between EST performance and cognitive and PD-related variables. CONCLUSIONS: Those PD patients with more severe forms of illness and a greater level of prefrontal cognitive dysfunction are more vulnerable to the distracting effects of external negative stimuli. According to the cognitive model of depression, this may ultimately lead to the development of clinical depression.

Adult↗

PubMed2001

[Sleep and intellectual functioning in the elderly: the role of sleep quality and apnea--literature survey].

In both relatively healthy and in demented elderly people mental abilities and sleep quality decrease in becoming older and nocturnal respiratory disturbance increases. Perhaps there is an association between sleep and cognition. The hypothesis that specific sleep phenomena are necessary to assure an adequate level of cognitive functioning is called the sleep cognition hypothesis. In this article the findings of research in older people are reviewed. 23 research reports were found in which sleep was measured with polysomnography. The findings in relatively healthy older people do not suggest a strong association between sleep and cognition nor a causal effect between a specific cognitive dysfunction and a specific sleep variable. The findings in demented older people concerning sleep and cognition are inconsistent. In relatively healthy older people a significant correlation between nocturnal respiratory disturbance and cognitive functioning was seldom found, whereas in demented older people a clear association was shown. Therefore, in demented older people prudence is necessary in prescribing psychopharmaca because these can enhance the appearance of sleep apneas.

Aged↗

PubMed2005

Integrating neurobiology and psychopathology into evidence-based treatment of social anxiety disorder.

Social anxiety disorder (SAD) is a common, chronic psychiatric disorder characterized by a persistent fear of social or performance situations in which embarrassment can occur. This disorder typically appears during the mid-adolescent years and is unremitting throughout life if not properly treated. SAD presents as two subtypes: the more common and debilitating generalized form, and the nongeneralized form, which consists predominantly of performance anxiety. The majority of patients with SAD have comorbid mental disorders, including mood, anxiety, and substance abuse. No single development theory has been proposed to account for the origins of SAD, although current understanding of the etiology of SAD posits an interaction between psychological and biological factors. Risk factors include environmental and parenting influences and dysfunctional cognitive and conditioning events in early childhood. The neurobiology of SAD appears to involve neurochemical dysfunction, as evidenced by studies of neuroreceptor imaging, neuroendocrine function, and profiles of response to specific medications. Clinical trials have demonstrated that benzodiazepines and antidepressants are effective in the treatment of SAD. The selective serotonin reuptake inhibitors are emerging as the first-line treatment for SAD, based on their proven safety, tolerability, and efficacy. Goals for ongoing future research include development of approaches to achieve remission, to convert nonresponders and partial responders to full responders, and to prevent relapse and maintain long-term efficacy. This monograph explores the epidemiology, clinical presentation, and differential diagnosis of SAD, with a focus on neural circuitry of social relationships and neurochemical dysfunction. The prevalence, rates of recognition and treatment, patterns of comorbidity, quality-of-life issues, and natural history of SAD are discussed as well as pharmacologic and psychosocial treatment strategies for SAD.

Adult↗

PubMed2002

[Higher brain dysfunction in benign childhood epilepsy with centrotemporal spike and atypical benign partial epilepsy of childhood].

Although some recent studies have reported various cognitive impairments and behavioral disorders in children having benign childhood epilepsy with centrotemporal spike (BCECT), it is still commonly believed that BCECT does not cause any definite neuropsychological impairment. In addition, reported impairments range over various cognitive functions, and there is no general agreement on this issue. We performed detailed neuropsychological tests in 17 children with BCECT and analyzed the profiles of their subtests. Atypical benign partial epilepsy of childhood (ABPE) is a type of BCECT in which patients have minor generalized seizures and their EEGs show continuous spike-waves during sleep. We also performed the same tests in five patients with ABPE, and compared the results in the two groups. Neuropsychological tests performed are as follows: Kaufman assessment battery for children (K-ABC), Wechsler intelligence scales for children-revised (WISC-R), Illinois test of psycholinguistic abilities (ITPA), Benton visual retention test (BVRT), Token test, calculation, figure copying task, letter copying task, line bisection task, and line cancellation task. Mental processing composite of the K-ABC and FIQ of the WISC-R were within normal limits in all children with BCECT and ABPE, but were generally lower in ABPE than in BCECT. On the other hand, the profiles of subtests of ITPA in children with BCECT revealed the significant feature of the lower scores on verbal expression (p = 0.013) and auditory sequential memory (p = 0.035). Considering the normal scores in the elementary cognitive functions, such as visual and verbal functions and long-term memory, disturbance in the process of executive functions such as flexibility, fluency, and working memory could cause this characteristic profile. ABPE also showed the similar profile in the subtests of ITPA to that of BCECT. It is likely that both groups of children share the common cognitive dysfunction.

Attention Deficit Disorder with Hyperactivity↗

PubMed1987

Mediational factors underlying cognitive changes and laterality in affective illness.

Affective illness has been associated with lateralized right hemisphere deficits and global cognitive dysfunction. However, there has been very little exploration of information-processing strategies that may underlie cognitive changes in this population. Twenty euthymic, drug-free, bipolar patients and 20 controls were given a series of tasks to assess lateralized impairment of the cerebral hemispheres and sequential (analytic) versus simultaneous (gestalt) information-processing strategies. There were no differences between patients and controls in tests sensitive to right or left hemisphere impairment or in total errors on a face recognition task. However, patients tended to rely on individual facial features for recognition whereas controls were able to synthesize multiple elements of the faces. Moreover, on a task that required holistic synthesis of multiple stimulus elements (Street Gestalt Completion Test), patients made significantly more errors than controls. Implications for information-processing changes in bipolar affective illness are discussed.

Adult↗

PubMedDate not supplied

Empirical assessment of the self-medication hypothesis among dually diagnosed inpatients.

The aim of this study was to empirically determine the expected effects of drugs of abuse on the psychiatric symptoms of individuals dependent on alcohol and other drugs to assess the validity of the self-medication hypothesis, defined as motivation of patients to seek a specific drug for relief of a particular set of symptoms. Eight-three inpatients in a large metropolitan hospital with an axis I diagnosis of one drug dependence and an axis II diagnosis of personality disorder completed the Hopkins Symptom Checklist-Revised (HSCL-90-R) and the Neuropsychological Impairment Scale (NIS). They also reported the effect of their drug of choice on each of the symptoms included in both tests. Heroin addicts reported that heroin improved some of their psychiatric symptoms and all of their cognitive dysfunctions. Both cocaine and alcohol users reported that their drug of choice worsened their psychiatric and cognitive symptoms. No relationship was found between frequency or severity of symptoms and drug choice. We concluded that attempts at self-medication may have occurred among heroin addicts, but were unlikely among alcoholics and cocaine addicts. We found no evidence in support of the self-medication hypothesis as a necessary reinforcer of continued drug use.

Adaptation, Psychological↗

PubMedDate not supplied

Correlation between the CAMCOG, the MMSE, and three clock drawing tests in a specialized outpatient psychogeriatric service.

Our objective was to assess the correlation between (1) the Cambridge Cognitive Examination (CAMCOG) (including the Mini-Mental State Examination [MMSE]) score and three clock drawing tests (CDT) and (2) the three CDTs independently, in a specialized outpatient psychogeriatric service. One hundred and fourteen subjects completed a comprehensive evaluation and were allocated to one of the following groups: dementia of the Alzheimer's type (DAT) in 52; vascular dementia (VD) in 36; non-dementia (ND; Mood or Anxiety Disorders) in 26. When the entire sample of patients is considered, all three CDTs used were highly and significantly correlated to the MMSE score, the CAMCOG score, and to each other. In this patient population, these cognitive tests may be interchangeable for providing an initial objective measure of cognitive function. However, when the same correlations were studied in the separate diagnostic groups, in the dementia group (DAT and VD) even though the high correlations between the various CDTs themselves did not change, the correlations between the MMSE score, the CAMCOG score and the CDTs decreased, more evidently in the VD group. This trend became even more conspicuous in the ND group, where some of the above mentioned correlations became non-significant. We hypothesize that in a real clinical situation the clinician initially assumes the role of cognitive "evaluator" (in terms of the total sample) followed by the role of cognitive "monitor" (in relation to specific diagnostic groups). In the first instance, CDTs, the MMSE, and the CAMCOG might be considered interchangeable as an initial objective measure of cognitive dysfunction, while in the second role, different CDTs might be diversely used, presumably supplemented by other cognitive tests and clinical methods.

Aged↗

PubMed1997

Cognitive enhancers in theory and practice: studies of the cholinergic hypothesis of cognitive deficits in Alzheimer's disease.

The current status of the cholinergic hypothesis of cognitive dysfunction in Alzheimer's disease is reviewed in the context of recent attempts to alleviate specific cognitive impairments produced in rats by excitotoxic lesions of basal forebrain neurons by treatment with cholinergic agents. AMPA-induced lesions of the nucleus basalis region in rats produce profound and relatively specific reductions in neocortical markers of cholinergic function but fail to affect performance in many tests of memory and learning in rats. However, such lesions produce specific deficits in responding accurately in a test of visual attentional performance, which are reversed dose-dependently by treatment with systemic physostigmine or nicotine. Analogous improvements have been reported in a clinical trial of the anticholinesterase tacrine in patients with Alzheimer's disease. By contrast, AMPA-induced lesions of the medial septum produce profound reductions in hippocampal acetylcholine and accompanying delay-dependent deficits in a delayed non-matching-to-position procedure which measures spatial working memory in rats. This impairment is shown to be reversed to some extent by treatment with low doses of physostigmine. The results are discussed in terms of the multivariate nature of the neurochemical pathology of Alzheimer's disease and attendant limitations in the use of the cholinergic strategy. The cognitive costs, as well as benefits, of cognitive enhancers are discussed, as well as the need to broaden our therapeutic approach to other neurotransmitter systems and other neurodegenerative disorders.

Alzheimer Disease↗

PubMed1995

The relationship between cognitive functions and behavioral deviance in children at risk for psychopathology.

Previous studies have generally found that children at risk for psychopathology (i.e. children characterized by risk factors such as parental psychopathology and maltreatment) display more deviant behavior and cognitive dysfunctions than children not at risk. The present study examined the relationship between behavioral deviance and cognition in children characterized by a variety of risk factors (parental schizophrenia, parental psychiatric disorders other than schizophrenia, parental maltreatment). The results indicated that the effects of parental schizophrenia could be distinguished from the more generalized effects of maltreatment and that cognitive deficits were associated with schizoid behavior in children at risk for schizophrenia. These findings suggest that cognitive ability may serve as a moderator of vulnerability to maladjustment in children at risk for schizophrenia.

Adolescent↗

PubMed2004

[Mild cognitive impairment].

It is essential to determine whether memory impairment is accompanied by impairment in other cognitive areas in patients presenting with the complaint of forgetfulness. Furthermore, it should be established whether this impairment is associated with normal aging or dementia. Several terms have been suggested to identify cognitive disorders without dementia. Benign senescent forgetfulness, age-associated memory impairment and aging-associated cognitive decline are considered to fall within the limits of normal aging. A recently proposed term, mild cognitive impairment, as opposed to the terms mentioned above, identifies a transitional state between normal aging and dementia. With the use of criteria proposed for mild cognitive impairment, this disorder converts to Alzheimer's disease at a rate of 10-15 % yearly. However, in longitudinal studies different neuropsychological tests and assessment scales were used for the diagnosis of mild cognitive impairment, resulting in different conversion rates to Alzheimer's disease. Recently, it has been proposed to classify mild cognitive impairment according to memory and non-memory involvement as amnestic, multiple domain and non-memory single domain clinical subtypes. Furthermore, vascular, metabolic, traumatic and various etiologies other than degenerative etiology are mentioned. Besides the medications known to be effective for cognitive dysfunctions, memory enhancement training is suggested for treatment. A consensus on the diagnostic criteria for mild cognitive impairment, determining the subgroups and further studies on treatment are necessary.

Cognition Disorders↗

PubMed1982

Auditory nerve-brain stem responses (ABR) in children with developmental brain disorders and in high risk neonates.

Auditory nerve-brain stem evoked responses (ABR) have been used for many years to evaluate auditory and neurological disorders. This study is devoted to the demonstration that ABRs can also contribute to the assessment of children with developmental brain disorders, e.g. psycho-motor retardation, minimal brain dysfunction, cerebral palsy and autism. The ABR in many of these children was abnormal, providing evidence for the presence of brain damage in these children which is probably responsible for the disorder they display. Since many of these children suffered from some congenital, perinatal or neonatal insult, ABR recording was also conducted in high risk neonates and young infants. Many of these neonates and infants had abnormal ABRs and, in several, there was improvement of the ABR upon repeated testing. These findings of abnormal ABRs in children with developmental brain disorders who suffered a perinatal insult and abnormal ABRs in neonates who suffered such an insult lead to the following hypothesis: a congenital-perinatal-neonatal insult can cause, at the time of its occurrence, some form of brain damage which may be demonstrated by abnormal ABRs. The same underlying brain damage may also cause developmental brain disorders which become apparent when he is older. Therefore ABR recording during the neonatal period may contribute to the early detection of brain dysfunction in at-risk neonates and may predict the later appearance of neurological, behavioural and cognitive dysfunctions. A longitudinal experimental protocol for the testing and evaluation of this hypothesis is presented.

Brain Diseases↗