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Impaired social response reversal. A case of 'acquired sociopathy'.

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.

Antisocial Personality Disorder↗

Neurologic and neurobehavioral effects of electric and lightning injuries.

There are few studies of the effects of electric and lightning injuries (ELI) on the neurologic and neuropsychological status of injured patients. We reviewed records of fourteen patients with ELI injuries seen at our hospital (12 with high-voltage electric and two with lightning injury). Eight had cardiac arrest after injury, and 10 had neurologic complaints when first evaluated. Eight had normal neuroimaging results. Six had electroencephalograms; four showed abnormal results. Thirteen underwent neuropsychological testing. Twelve (92%) showed cognitive dysfunction including impairments in memory, attention, and affective disturbances (anxiety, depression, irritability, and poor frustration tolerance). Five of 12 (62%) had multiple physically aggressive outbursts, not present before the injury. Patients with cardiac arrest did not differ in neurologic psychologic testing from patients not sustaining cardiac arrest. Patients with ELI who had neurobehavioral symptoms had a coherent syndrome characterized by disturbances in cognition (attention and memory), mood (distress with prominent irritability), and behavior (aggressive outbursts). Serial neurologic and neuropsychological evaluations will aid in better defining the sequelae of ELI.

Adult↗

[The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder].

The aim of this study was to assess the effect of sertraline on psychopathological symptoms and cognitive functions and in patients with obsessive compulsive disorder (OCD). The investigated group consisted of 25 patients with OCD (12 male, 13 female) aged 17-47 (mean 29 +/- 9) years, duration of illness was 1-15 (mean 4 +/- 2) years. After treatment with sertraline, a significant improvement in OCD symptoms measured by YBOCS and in neuropsychological "frontal" tests were observed. Little correlation was found between the effect of sertraline on OCD symptoms and on cognitive dysfunctions. This may suggest that these two effects may be connected with different pharmacological properties of the drug. The effect of sertraline on OCD symptoms, similarly like other drugs inhibiting serotonin transporter (clomipramine, other SSRI) is associated with its influence on serotonergic system. On the other hand, the effect of sertraline on dopaminergic neurotransmission may be related to its favorable action on cognitive functions connected with the activity of frontal lobe.

Adolescent↗

Neuropsychological impairment and quality of life in obstructive sleep apnea.

Although clinical experience has suggested for more than two decades that OSA is associated with impairment of cognition, emotional state, and quality of life and that treatment with nasal CPAP produces significant improvements in these areas, sound empirical evidence to support this view, especially regarding treatment outcome, has been lacking. More recent investigations have begun to provide this support from randomized, adequately controlled studies. These assessments suggest that some degree of cognitive dysfunction is associated with OSA. The effects are most apparent in the severe cases, whereas results in mild cases are more equivocal. Reported impairments include global intellectual dysfunction and deficits in vigilance, alertness, concentration, short- and long-term memory, and executive and motor function. Considerable discrepancy exists across studies with respect to type and degree of dysfunction, however. Disturbances in general intellectual function and executive function show strongest correlations with measures of hypoxemia. Not unexpectedly, alterations in vigilance, alertness, and, to some extent, memory seem to correlate more with measures of sleep disruption. Although many inadequately controlled investigations have demonstrated reversibility of most or all of these deficits with effective treatment, more recent placebo-controlled studies have raised doubts regarding whether the observed changes are truly a function of treatment. This issue requires further systematic exploration with adequate controls and step-wise analysis of treatment duration effects. A similar set of considerations exists with respect to the relationship between psychological disturbance, primarily depression, and OSA. Although several studies suggest significant depression in these patients, the results are mixed. Placebo-controlled treatment trials fail to demonstrate consistently a difference in mood improvement between active treatment groups and controls, although several methodologic considerations suggest that these results should be interpreted with caution. Numerous investigations leave little doubt about the issue of quality of life impairment among persons with OSA. Further characterization of impairment, particularly in areas specific to this population, will provide clearer understanding of the problem. Preliminary investigations of treatment response in controlled studies indicate significantly greater improvement of quality of life in response to CPAP. Although patients with OSA commonly report disturbances in cognitive and psychological function and general quality of life, the increased rates of obesity, hypertension, diabetes, cardiovascular disease, medication use, and related psychosocial complications present a host of potential etiologies that might explain the impairments noted. There can be little doubt that these covariants do, in some cases, contribute to neuropsychological dysfunctions. It is essential that future studies continue to define those disturbances that are specific to OSA, the relationship between levels of severity and impairment, the role of treatment in reversing these dysfunctions, and the correlation between test results and significant day-to-day social and occupational functional impairment.

Clinical Trials as Topic↗

PD 142676 (CI 1002), a novel anticholinesterase and muscarinic antagonist.

Inhibition of brain acetylcholinesterase (AChE) can provide relief from the cognitive loss associated with Alzheimer's disease (AD). However, unwanted peripheral side effects often limit the usefulness of the available anticholinesterases. Recently, we identified a dihydroquinazoline compound, PD 142676 (CI 1002) that is a potent anticholinesterase and a functional muscarinic antagonist at higher concentrations. Peripherally, PD 142676, unlike other anticholinesterases, inhibits gastrointestinal motility in rats, an effect consistent with its muscarinic antagonist properties. Centrally, the compound acts as a cholinomimetic. In rats, PD 142676 decreases core body temperature. It also increases neocortical arousal, as measured by quantitative electroencephalography, and cortical acetylcholine levels, measured by in vivo microdialysis. The compound improves the performance of C57/B10j mice in a water maze task and of aged rhesus monkeys in a delayed match-to-sample task involving short-term memory. The combined effect of AChE inhibition and muscarinic antagonism distinguishes PD 142676 from other anticholinesterases, and may be useful in treating the cognitive dysfunction of AD and produce fewer peripheral side effects.

Animals↗

Relationships between cognition and structural neuroimaging findings in adults with human immunodeficiency virus type-1.

Infection of the central nervous system with human immunodeficiency virus type-1 (HIV) is associated with cognitive impairments that range from mild cognitive and motor difficulties to dementia. Structural neuroimaging abnormalities are also common in HIV-infected patients both with and without cognitive disturbances. The most common abnormalities include high signal intensities in the white matter and atrophy. Research over the past 12 years has helped define the relationship between these neuroimaging abnormalities and the manifestation of cognitive disturbance in HIV. In the present paper, we provide a synopsis of these studies and report the current state of the literature. Our review revealed that atrophy of the caudate nucleus is most consistently associated with cognitive impairment in HIV. The current literature does not support a strong relationship between cortical atrophy or white matter abnormalities and cognitive dysfunction in this population, though methodological issues may have influenced the results. Suggestions for study design and new research directions are provided.

Acquired Immunodeficiency Syndrome↗

Cognitive functions in survivors of primary central nervous system lymphoma.

BACKGROUND: The standard treatment for primary CNS lymphoma (PCNSL) involves high-dose methotrexate-based (MTX) chemotherapy and whole brain radiotherapy (WBRT). This combined regimen prolongs patient survival, but also carries a substantial risk for delayed neurotoxicity particularly in the elderly. However, cognitive outcome evaluations have not been included in most clinical trials. OBJECTIVE: To assess cognitive functioning and quality of life in PCNSL survivors treated either with WBRT +/- MTX-based chemotherapy or chemotherapy alone. METHODS: Twenty-eight PCNSL patients in disease remission received a post-treatment baseline neuropsychological evaluation, and a subset of patients were available for an 8-month follow-up evaluation. Assessment of quality of life and extent of white matter disease on MRI were also performed. RESULTS: Patients displayed mild to moderate impairments across several cognitive domains. These were of sufficient severity to reduce quality of life in half of the patient sample. Comparisons according to treatment type revealed more pronounced cognitive impairment, particularly in the memory and attention/executive domains, among patients treated with WBRT +/- chemotherapy. Extent of white matter disease correlated with attention/executive, memory, and language impairment. CONCLUSIONS: PCNSL survivors treated with WBRT +/- chemotherapy displayed more pronounced cognitive dysfunction than patients treated with MTX-based chemotherapy alone.

Adult↗

Discourse analyses with closed head injured adults: evidence for differing patterns of deficits.

To better characterize the verbal impairments of higher level closed head injured (CHI) adults, we used narrative stories to longitudinally sample their discourse abilities. Stories were analyzed at the levels of intersentential cohesion and story grammar. Two differing patterns of deficits that emerged are described. In the first, a CHI subject demonstrated excessive verbalization characterized by poorly organized, but task-appropriate, content. In the second, a CHI subject demonstrated fair to good organization but little appropriate content. Prognostically, the presence of appropriate, although disorganized, content was an early indication that the subject was able to appreciate potential relationships of characters in the stimulus picture. The second pattern represented a more severe cognitive dysfunction. This subject's attempts at stories, although well organized, were merely elaborate descriptions of the picture. Discourse analyses appear to be well suited for the assessment of CHI adults.

Adult↗

Neuropsychology and multiple sclerosis: diagnostic and rehabilitative approaches.

The frequency of cognitive deficits in multiple sclerosis (MS) patients is rather high and the estimates vary between 43% and 72% depending on the patient samples studied as well as on the methods of cognitive assessment. Despite the great impact of cognitive dysfunction on several aspects of the quality of life, the importance of accurate assessment and rehabilitation of neuropsychological deficits in MS patients has long been ignored. In this article, we first describe tests for the assessment of impairments, disabilities and handicaps. We emphasize that after screening with brief assessment instruments, detailed testing of the basic target deficits is mandatory for the planning of special cognitive training programs. Second, the correlation of certain cognitive deficit patterns with important magnetic resonance imaging (MRI) variables such as total lesion area, size of the corpus callosum and specific lesion location is outlined in detail. Third, some recommendations are made with regard to general rehabilitation principles such as restitution, compensation and adaptation as well as for special rehabilitation techniques including cognitive retraining of basic deficits and/or training of activities of daily living. Finally, we emphasize that there is a need for the development of tailor-made neuropsychological rehabilitation techniques for MS patients, which take into account the course and stage of the disease as well as the specific psychosocial problems of the individual patient.

Adult↗

Effects of blood lead levels on cognitive function of older women.

Elevated blood lead concentrations are known to have detrimental effects on neuropsychological function in both children and occupational cohorts of men and women. Although it is generally accepted that lead exposure at low levels is more dangerous for infants and children than for adults, the issue of the lowest level of exposure at which lead causes deleterious health effects in adults is yet to be solved. There is no available data on the role of lead exposure in cognitive dysfunction in nonoccupational cohorts of older persons. In the current study, we examined the cross-sectional relationship between blood lead levels and a variety of measures of neuropsychological function in a large cohort of elderly women recruited at both urban and rural sites. This study of elderly women demonstrates that blood lead levels as low as 8 micrograms/dl were significantly associated with poorer cognitive function as measured by certain neuropsychological tests. Even a slight decrement in cognition would have a large public health impact due to the large number of elderly at risk.

Adult↗

Cortisol suppression by dexamethasone in the healthy elderly: effects of age, dexamethasone levels, and cognitive function.

The effects of age, cognitive function (measured by Cambridge cognitive examination (CAM-COG) score); and dexamethasone (DEX) levels on the dexamethasone suppression test were studied in 33 healthy older subjects (age 51-96). Three subjects (9.1%) were nonsuppressors and were older and had lower CAMCOG scores than the 30 suppressors. Significant correlations were observed between natural log-transformed postdexamethasone cortisol (LNCOR) levels and age (r = 0.40) and CAMCOG score (r = -0.45). Multiple regression analysis was used to investigate the relationship between LNCOR, age, DEX levels, and CAMCOG score. Age and DEX combined explained 41% of the variance in LNCOR values, whereas CAMCOG score and DEX levels explained 44% variance. As age and CAMCOG were highly correlated (r = -0.72), both together did not significantly improve the fit of regression equation (47% variance explained). These findings suggest an association between advancing age, impaired glucocorticoid feedback, and cognitive dysfunction in healthy human subjects. Although any causal connection remains to be demonstrated, results would be consistent with the "glucocorticoid cascade" hypothesis of human aging.

Aged↗

Left-right spatial agnosia and other mental defects that characterize clinical researchers.

There are mathematical rules for determining the logical significance of data, just as there are such rules for determining the statistical significance of data. Logical significance reflects the question a study is asking, whereas statistical significance reflects how well it has been answered. Clinical researchers routinely make an incorrect determination as to their study's logical significance because of a spatial (left-right) agnosia. More diffuse cognitive dysfunctions are encouraged by journals that expect clinicians to report on a study as a prerequisite for communicating their pre-existing opinions. The unwillingness or inability of the clinical community to acknowledge this problem reflects a related anosagnosia.

Agnosia↗

Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study.

As part of a prospective study of neurological and neuropsychological complications of coronary bypass surgery, 259 patients underwent psychometric assessment before operation and at seven days and six months after operation using a battery of 10 standard tests of intellectual function. This report describes the natural history of intellectual dysfunction soon after surgery and the incidence and functional impact of late neuropsychological impairment. The mean neuropsychological scores for the whole group remained unchanged or improved compared with levels before operation for the majority of the 10 tests. Analysis of the test scores for individuals showed that 147 of 259 (57 per cent) patients showed deterioration on at least one test score at six months. The degree of impairment was usually mild. One hundred and thirty of the 147 patients showed mild cognitive dysfunction (score deterioration on one or two tests) and only 17 patients had moderate or severe impairment (score deterioration on three or more tests). Detectable neuropsychological deterioration at six months often did not matter to the patient in functional terms. Seventy-one per cent of these patients had no significant symptoms; 27 per cent had minor symptoms and only 2 per cent were seriously disabled. Of the patients unemployed at six months, in only one case was intellectual impairment the factor preventing return to work. A search for possible predisposing factors for long-term intellectual dysfunction was made using a multivariate analysis of 91 variables for each patient. Cardiac failure before surgery and global impairment of left ventricular function were the only factors showing significant correlation.

Adult↗

Cognitive function after anaesthesia in the elderly.

Despite advances in peri operative care, a significant percentage of elderly patients experience transient post operative delirium and/or long-term post-operative cognitive dysfunction (POCD). This chapter reviews the aetiology, clinical features, preventive strategies and treatment of these syndromes. Pre-operative, intra-operative, and post-operative risk factors for delirium and POCD following cardiac and non-cardiac surgery are discussed. It is most likely that the aetiology of delirium and POCD is multifactorial and may include factors such as age, decreased pre-operative cognitive function, general health status and, possibly, intra-operative events. Currently there is no single therapy that can be recommended for treating post-operative cognitive deterioration. Primary prevention of delirium and POCD is probably the most effective treatment strategy. Several large clinical trials show the effectiveness of multicomponent intervention protocols that are designed to target well-documented risk factors in order to reduce the incidence of post-operative delirium and, possibly, POCD in the elderly.

Aged↗

Neuropsychological test performance in the acquired immunodeficiency syndrome: independent effects of diagnostic group on functioning.

Individuals infected with the acquired immunodeficiency syndrome (AIDS) are at risk for developing cognitive impairment. The extent to which the impairment represents the results of a single factor accounting for a wide degree of cognitive dysfunction, or is the result of the combined effects of multiple factors, has not been determined. In the present study, we analyzed data from 134 patients with AIDS and 105 HIV- controls using a recently developed analytical procedure. The results revealed that, by and large, the test variables shared a significant amount of variance related to disease status. Hence the AIDS-related influences on cognition are shared and thus cannot be considered independent. Two tests, Digit Symbol Substitution, and the primary measure of verbal free recall, had a direct relationship with the group variable (AIDS vs. controls). These results suggest that a single factor is sufficient to account for a large proportion of the AIDS-related variance on a wide variety of neuropsychological tests.

AIDS Dementia Complex↗

A hypnotically mediated guided imagery intervention for intrusive imagery: creating ground for figure.

Intrusive imagery can be seen as a cognitive dysfunction in the assimilation and accommodation of the psychological material represented by those images. From a gestalt psychological perspective, the intrusive image represents a figure without a ground that can provide meaning and context. Hypnotically mediated guided imagery interventions can be used to create a ground for the rogue image that metaphorically is an unassimilated figure; and thus allow for the creation of a new cognitive scheme. Four case examples are presented as well as a model for the intervention.

Adult↗

Improving metabolic control leads to better working memory in adults with type 2 diabetes.

OBJECTIVE: The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance. RESEARCH DESIGN AND METHODS: This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery. RESULTS: Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1-2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG. CONCLUSIONS: Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.

Adult↗

Pattern of impaired working memory during major depression.

BACKGROUND: The aim of this study was to assess working memory (WM) in patients with major depressive disorder (MDD), using a robust parametric WM task (the n-back task). METHODS: Twenty patients with MDD and twenty healthy controls completed a visual version of the paradigm, comprising four levels of task difficulty (i.e. 0-, 1-, 2-, and 3-back). Performance accuracy and reaction time (RT) were measured at each difficulty level. RESULTS: In comparison with controls, patients with MDD exhibited slower RTs (F((1,38)) = 25.16, p < 0.001), and reduced accuracy (F((1,38)) = 5.93, p < 0.001). There was no diagnosis-specific effect of task difficulty on performance accuracy. However, the faster response to memory (1-3-back) than to shadowing (0-back) tasks observed in controls was not as pronounced in patients. CONCLUSIONS: These observations support a relatively specific impairment of WM/central executive function in MDD, which may potentially mediate the diverse pattern of cognitive dysfunction noted in MDD. The parametric n-back task is applicable to subjects with MDD and yields results interpretable across the dimensions of task difficulty and performance in controls and patients.

Adult↗

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