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The need to relate cognitive deficits to specific behavioral referents of schizophrenia.

The implicit rationale for many cognitive studies of schizophrenia hinges on the recognition that verbal communication generated by patients with this disorder is often elusive or difficult to comprehend. This observation has led to the inference that a cognitive dysfunction, which mediates the production of discourse failure, is characteristic of schizophrenia. Unfortunately, most investigators have chosen to examine this type of hypothesis by comparing heterogeneous groups of schizophrenic patients (without regard to whether they exhibit verbal communication impairment) with various control samples; they have not studied the association between cognitive processes and specific schizophrenic symptoms. Data are presented from two studies indicating that such relationships, even when highly plausible, cannot simply be presumed. In both studies, one with adults suffering from schizophrenia and the other with children at risk, a laboratory measure of referential communication failed to be strongly related to language disorder. These data suggest that future investigators should specify the features of schizophrenia that are expected to correlate with their laboratory measures and empirically evaluate these relations.

Adult↗

The spectrum of idiopathic Rolandic epilepsy syndromes and idiopathic occipital epilepsies: from the benign to the disabling.

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is an idiopathic focal epilepsy syndrome, the benign characteristics of which are debated; in fact, stable or intermittent specific neuropsychological deficits are frequent and may affect scholastic or adaptive abilities. Cognitive dysfunction may be related to a marked increment of the interictal epileptic discharges in NREM sleep: different degrees of neuropsychological deficits depend on the extent of awake and sleep activity and the predominant discharge localization. The age of onset and duration of atypical sleep EEG patterns may correlate with permanent cognitive impairments. These atypical clinical and EEG evolutions have been reported in the literature as different syndromes that constitute the spectrum of idiopathic rolandic epilepsy. Moreover, a clinical link between BCECTS and early-onset benign childhood occipital epilepsy has been demonstrated. According to the neurobiological approach, the spectrum of Idiopathic Rolandic Epilepsy is based on an age-dependent, idiopathic predisposition to focal seizures and sharp-wave discharges, as an expression of nonlesional cortical excitability. The involvement of a given area of the cerebral cortex may depend on the brain maturational stage.

Age Factors↗

Delirium among elderly persons admitted to a psychiatric hospital: clinical course during the acute stage and one-year follow-up.

Seventy elderly patients meeting the DSM-III criteria for delirium were examined during the acute stage and followed up to one year. The mean age of the patients was 75 years (range 60-88), their delirium lasted on average 20 days (range 3-81) and the psychiatric hospitalization on average 30 days (range 8-365). The most common etiologies for delirium were stroke, infections and metabolic disorders. For 57 cases (81%) a predisposing structural brain disease was found. During the index admission, the cognitive dysfunction associated with delirium ameliorated significantly (the mean +/- SD Mini-Mental State Examination score 9.7 +/- 6.6 at admission and 13.9 +/- 7.2 at discharge; P less than 0.001), but during the one-year follow-up progression of the basic central nervous system disease was seen together with declining cognition and deterioration of functions of daily living.

Activities of Daily Living↗

The relationship of the Allen Cognitive Level Test to cognitive abilities and psychopathology.

The cognitive factors measured by the Allen Cognitive Level Test (ACL) (Allen, 1982) as well as the test's relationship to level of psychopathology were examined through a retrospective study of 71 patients from a general hospital psychiatry unit. Pearson correlations, computed for the ACL score with the Shipley Institute of Living Scale (Shipley, 1940), a general measure of intellectual functioning, were significant. A strong correlation was found between the ACL and the Symbol-Digit Modalities Test (Smith, 1982), a measure of motor speed and concentration often used as a neurological screening instrument. This suggests the potential usefulness of the ACL to screen for cognitive dysfunctions associated with organicity. Contrary to hypothesis, there was no significant correlation between the ACL and measures of psychopathology such as the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) and the Minnesota Multiphasic Personality Inventory (Hathaway & McKinley, 1940). The relationship of the ACL to other recognized measures of cognitive functioning increases its usefulness as a valid measure of day-to-day limitations in the functioning of psychiatric patients. Effective communication of the implications of these cognitive levels to a multidisciplinary treatment team is enhanced by knowledge of the relationship of the ACL to measures of cognitive functioning and psychopathology used by other disciplines.

Adult↗

[Specific developmental disorders and the family--pathogenetic factors in children with behavioral disorders].

121 children aged 5;6 to 8;6 years referred to our center as out-patients because of various types of behavioral problems and showing distinct symptoms of minor neurological dysfunction were investigated with regard to family-related variables, specific developmental disorders, and the extent of the behavioral problems. A comparison of the groups with few and numerous behavioral problems showed a significant difference in the number of familial risk factors, but not in the degree of neurological and cognitive dysfunction. These results indicate the importance of child-independent familial factors, e.g. marital problems and psychosocial stress, in the pathogenesis of behavioral disturbances in children with minor neurological dysfunction. The resulting need for a family-oriented perspective in assessment and therapy is discussed.

Attention Deficit Disorder with Hyperactivity↗

The Alzheimer's Disease Assessment Scale-Cognitive subscale: normative data for older adult controls.

The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) is commonly used to assess cognitive dysfunction in individuals with Alzheimer disease and other dementias. The purpose of this study was to provide normative scores for the ADAS-cog 11 individual items and total score, as well for delayed recall errors, using normal, elderly volunteers. The ADAS-cog was administered to 124, non-cognitively impaired volunteers ages 55 to 89, with 10 to 21 years of education. The mean total ADAS-cog score was five. The ADAS-cog error score was not associated with education in this highly educated group, and was positively correlated (P < 0.001) with the age of the participant. Age stratified ADAS-cog normative data are reported for the ADAS-cog total and the delayed recall error score.

Age Factors↗

Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance.

The antiamnesic effects of bifemelane hydrochloride (bifemelane) and indeloxazine hydrochloride (indeloxazine) on radial maze performance in rats were assessed. This performance was dependent on working memory and spatial memory, without aversive electric stimuli. When administered alone, neither bifemelane nor indeloxazine had an effect on the task performance of normal rats. However, impairment of the performance of rats induced by scopolamine hydrobromide (scopolamine) injection was dose-dependently reduced by oral treatment with bifemelane. On the other hand, indeloxazine, which was reported to enhance the learning behavior in a passive avoidance test, did not improve the radial maze task performance of scopolamine-treated rats. It has been shown that dysfunction of the cholinergic neuronal system plays an important role in memory loss and that bifemelane induces recovery of reduced cerebral cholinergic neuronal activity associated with brain ischemia or aging. In accordance with these previous findings, our results suggest that bifemelane is useful in the treatment of memory loss and cognitive dysfunction in patients with dementia and cerebrovascular disease.

Animals↗

Psychometric characteristics in patients with frontal lobe degeneration of non-Alzheimer type.

Twenty patients, selected from a longitudinal study of patients with presenile and senile dementia, underwent psychometric assessment including semi-structured observations of behaviour in the test situation and examination for dysphasia. The patients were chosen on the basis of post-mortem investigation and showed frontal lobe degeneration (FLD) of non-Alzheimer type in 16 cases and Pick's disease in four cases. The patients are described with reference to cognition, language function, behaviour and emotional reactions in the test situation. The test results were analyzed and compared with psychometric results from other groups of demented patients, above all with Alzheimer's disease. The cognitive dysfunction was less severe in patients with onset of dementia below the age of 56 years as compared to patients with later onset, i.e., 56 years or older. Dysfunction of expressive speech was the most consistent finding in the patients with frontal lobe degeneration, while receptive speech functions were relatively less frequently affected.

Adult↗

Visuospatial working memory in patients with schizophrenia.

Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The "scratch pad's" passive visual store--responsible for the temporary retention of visual material--was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem--specialized for retaining the temporal properties--was explored through visual block span. To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia.

Adult↗

Cognitive functioning after whiplash injury: a meta-analysis.

Complaints on cognitive functioning are often reported in patients suffering from whiplash syndrome, although objective neuropsychological test results do not always support these. In addition, radiological abnormalities and anatomical lesions are found only in a minority of these patients. This has led to a controversy about its existence in the literature. In this systematic review, the results of 22 neuropsychological studies on whiplash were quantitatively analyzed, focusing on working memory, attention, immediate and delayed recall, visuomotor tracking, and cognitive flexibility. Our findings suggest that a consistent overall pattern of cognitive dysfunction can be demonstrated after whiplash injury through neuropsychological testing, both compared to healthy and to asymptomatic controls. Six months after the accident, improvement is found in working memory, attention, immediate recall, and visuomotor tracking. The results are discussed in the light of recent findings on the effect of cerebral dysfunction, malingering, pain-related factors, and the role of coping strategies and posttraumatic stress on neuropsychological test performance.

Brain Injury, Chronic↗

[Depression and dementia].

Specific symptoms of depression in aged subjects are presented in the paper. Cognitive dysfunctions in elder depressive patients (so called pseudodementia) as well as comorbidity of dementia with depression are special diagnostic problems. Both etiopathogenetic and clinical issues are discussed.

Aged↗

[Evaluation of subjective experience of cognitive deficit in patients with schizophrenia using the Eppendorf Schizophrenia Inventory].

Presented is a new questionnaire--Eppendorf Schizophrenia Inventory (ESI)--for evaluation of subjective experience of cognitive dysfunction characteristic of schizophrenia and data that confirmed reliability and diagnostic validity of the ESI. The ESI is suggested to be an additional method of psychopathological diagnosis of schizophrenic disorders.

Cognition Disorders↗

Targeting information-processing deficit in schizophrenia: a novel approach to psychotherapeutic drug discovery.

Current observations indicate that dysfunction of neuronal circuitry dynamics contributes to the abnormal information processing in the brain in schizophrenia. It is presumed that disrupted auditory gating, abnormal P300-evoked potentials and deficits in mismatch negativity in schizophrenic patients indicate impaired processing of information. Recently, abnormalities in neuronal synchrony and oscillatory activity have been postulated as the mechanisms that underlie the distorted perception and cognitive dysfunction associated with schizophrenia. These novel observations might reveal the pathophysiology of the disorder, and indicate potential targets for antipsychotic drug therapy. Neuronal circuitry dynamics, such as network oscillations and sensory-gating processes, are conserved phylogenetically, which provides excellent opportunities for designing translational biomarkers. Whether preclinical, experimental compounds that impact on network oscillations and sensory processing (such as agonists and modulators of alpha7 nicotinic acetylcholine receptors) elicit the same neurophysiological events in schizophrenic patients and, subsequently, improve perception and cognitive functions will be determined when these drug candidates are available clinically.

Animals↗

Parental rearing style: examining for links with personality vulnerability factors for depression.

Recent research provides evidence of links between anomalous parenting experiences in childhood and subsequent depression. A study was designed to pursue the possibility that anomalous parenting effects a diathesis to depression by inducing a vulnerable cognitive style rather than by disposing directly to depression. Possible mediating personality style variables were explored in a study of 123 depressed subjects who scored their parents on the Parental Bonding Instrument (PBI), as well as completing a state depression and several relevant personality measures. Low self-esteem and a related dysfunction cognitive style were the personality variables most clearly linked with PBI scores, with links persisting after partialling out state levels of depression. Failure to find links between PBI scores and depression levels limited explication of the diathesis stress model.

Adult↗

Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.

OBJECTIVE: To assess the safety and tolerability of lexipafant in HIV-associated cognitive impairment. BACKGROUND: Cognitive impairment is the most common neurologic complication of advanced HIV-1 infection. There is evidence that a variety of inflammatory mediators, including platelet-activating factor (PAF), may contribute to neuronal injury. We hypothesized that lexipafant, a PAF antagonist, might improve cognitive dysfunction in HIV-infected people. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the safety and tolerability of lexipafant 500 mg/day. The primary outcome measure for tolerability was the ability to complete the study on the originally assigned dosage of medication. Thirty patients with cognitive impairment were enrolled. RESULTS: Lexipafant was safe and well tolerated. Ninety-three percent in the placebo group and 88% in the lexipafant group completed the study at the originally assigned dosage. Trends toward improvement were seen in neuropsychological performance, especially verbal memory, in the lexipafant treatment group. CONCLUSIONS: This study shows that lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment, is a safe and well tolerated compound. The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance.

Adult↗

Nimodipine. A review of its pharmacological properties, and therapeutic efficacy in cerebral disorders.

Nimodipine is a dihydropyridine calcium antagonist which dilates cerebral blood vessels and increases cerebral blood flow in animals and humans. Preliminary findings reveal its potential benefit for the treatment of a wide range of cerebrovascular disorders, particularly for prophylaxis and treatment of delayed ischaemic neurological deficits resulting from cerebral vasospasm in patients with subarachnoid haemorrhage. Studies involving patients aged up to 79 years have confirmed these preliminary findings by showing that nimodipine reduces the incidence of severe ischaemic deficit after subarachnoid haemorrhage. Initial results from studies of patients with acute ischaemic stroke indicate that nimodipine, started within 72 hours of onset, improved recovery, particularly in patients over 65 years. However, other investigators have found no marked difference in 6-month mortality or morbidity rates of stroke patients aged up to 97 years. Findings from other studies suggest that nimodipine may improve symptoms of cognitive dysfunction in elderly patients. Nimodipine is well tolerated by both younger and older patients. The most frequently reported adverse event has been hypotension. Thus, nimodipine therapy offers important benefits as part of the approach to management of patients with subarachnoid haemorrhage and has potential in other cerebral disorders, including stroke and impaired cognitive function, although confirmation of initial results in patients with cerebral impairment are required.

Aged↗

Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI.

BACKGROUND: Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer disease (AD). Recent reports suggest that heterozygosity for the two common hfe mutations responsible for hereditary hemochromatosis (HH) may be a risk factor for AD, possibly by accelerating brain iron accumulation. METHODS: To test this hypothesis, we genotyped 213 sporadic AD, 106 MCI, and 63 normal elderly control (NEC) individuals for the H63D and C282Y hfe mutations by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) analysis. We determined the relationship of these mutations to the demographic, clinical, and neuropsychological features of AD and MCI, and evaluated whether an interaction existed between hfe and apolipoprotein E (apoE) status in these patients. RESULTS: We observed no significant impact of H63D or C282Y heterozygosity on age at AD symptoms onset or diagnosis, age at onset of cognitive symptoms (AD and MCI combined), rates of MCI-to-AD conversion or specific neuropsychological deficits. No interactions between hfe zygosity and apoE status were discerned. Patients homozygous for H63D exhibited trends towards accelerated MCI-to-AD conversion rates and a subset of younger individuals (aged 55-75) exhibited earlier onset of cognitive symptoms relative to wild-type hfe and H63D heterozygotes. CONCLUSIONS: Contrary to earlier reports, the results of the present study do not implicate the common hfe mutations as genetic modifiers of sporadic AD and MCI. Trends towards accelerated cognitive dysfunction in H63D homozygotes warrant further study.

Aged↗

Cognitive functioning in Gulf War Illness.

A comprehensive neuropsychological battery was administered to 48 veterans with Gulf War Illness (GWI) characterized by severe fatigue (GV-F) and 39 healthy veterans (GV-H). Subjects were matched on intelligence and did not differ on age, gender, race, and alcohol consumption. Compared to GVs-H, GVs-F were significantly impaired on four tasks: three attention, concentration, information processing tasks and one measure of abstraction and conceptualization. After considering the presence of post-war Axis I psychopathology, GWI remained a significant predictor of cognitive performance on one of the attention, concentration, and information processing tasks and one abstraction and conceptualization measure. Performance on the remaining two attention, concentration, and information processing tasks was only significantly predicted by Axis I psychopathology with post-war onset. The results suggest that Gulf War Illness is associated with some aspects of cognitive dysfunction in Gulf Veterans, over and above the contribution of psychopathology.

Adult↗