Cognitive deficits in schizophrenia: an updated metanalysis of the scientific evidence

ABSTRACT: BACKGROUND: This is an update of a previous meta-analysis published in 2005. METHODS: It includes the data published up to march 2010 for a total of 247 papers and 18,300 cases. Cognitive deficits are examined in 5 different domains: Memory functioning (128 studies), Global cognitive functioning (131 studies), Language (70 studies), Executive function (67 studies), Attention (76 studies). Only controlled studies were included: patients vs. normal subjects. RESULTS: Results evidence that in all domains and in all different analyses performed within each domain, patients show a significant reduction of cognitive efficiency with respect to normal subjects. The between studies heterogeneity is very high in almost all domains. There are various sources of this heterogeneity (age, sex, sample size, type of patients, and type of measurement) which contribute to the high degree of not-overlapping information offered by the single studies. CONCLUSIONS: Our results, based on the current scientific evidence, confirm the previous findings that there is a generalized impairment of various cognitive functions in patients with schizophrenia when compared to normal cases. The modalities with which these results are obtained have not changed over the years and the more recent studies do not modify the high heterogeneity previously found between the studies. This reduces the methodological quality of the results. In order to improve the methodological quality of the studies performed in the field of cognitive deficits of patients with schizophrenia, various factors should be taken into account and better managed in designing future studies.     

The admissibility of expert evidence in Canada

Recent decisions in Canadian Law suggest that it is evolving in a manner heavily influenced by American law. A recent Supreme Court decision uses the framework of prevailing law and superimposes the more stringent criteria enunciated in Daubert v. Merrell Dow Pharmaceuticals, Inc. We trace this development, reviewing the intervening cases that have contributed, and conclude with a summary of the law as it stands today.     

The olfactory and cognitive deficits of Parkinson's disease: evidence for independence

In the present study we sought to determine whether the olfactory deficits of parkinsonism are related to the cognitive and perceptual-motor manifestations of the disease. Pearson correlation coefficients were computed among a number of olfactory, neurological, and neuropsychological measures obtained from 58 Parkinson's disease patients, including the University of Pennsylvania Smell Identification Test, a modified Randt memory test, a reaction time test, a finger-tapping test, ratings of motor and neurological function, and selected verbal and performance subtests of the Wechsler Adult Intelligence Scale--Revised. Data from 38 patients with Parkinson's disease who received odor detection threshold testing were also evaluated. The intercorrelation matrix was subjected to a principal components factor analysis which yielded six clear-cut factors: cognitive/memory, gross motor, oral motor, fine motor, olfactory, and tremor. The olfactory factor received strong and nearly exclusive loadings from the olfactory measures (which did not evidence meaningful loadings on any of the other factors). A ten-trial jackknife procedure revealed the factor structure to be stable. Further support of the independence of the olfactory variables from the other measures was provided by multiple regression and canonical correlation analyses. Overall, these findings lend support to the hypothesis that the olfactory disorder of parkinsonism is independent of the cognitive, perceptual-motor, and memory manifestations of the disease.     

Verbal memory in schizophrenia: additional evidence of subtypes having different cognitive deficits

A prior study found a selective deficit in verbal working memory in a subgroup of patients with schizophrenia who performed as well as healthy controls on a screening test of attention and auditory perception [Arch. Gen. Psychiatry 55 (1998) 1093]. Given the importance of defining pathophysiologically distinct subtypes of schizophrenia, the present study aimed to replicate and extend this finding. Patients with schizophrenia who passed the screening test (discriminators or Dsz patients) were compared to those who did not (nondiscriminators, NDsz patients), and healthy controls on a word serial position test (WSPT) and on other tests of verbal and nonverbal cognitive function. Dsz patients performed more poorly than controls on the WSPT and showed serial position effects consistent with a verbal memory deficit. They also showed a deficit in verbal memory but not visual memory on the Wechsler Memory Scale-Revised. In contrast, the NDsz patients showed overall poor performance on both verbal and nonverbal tests, consistent with a generalized deficit. Verbal working memory deficits were not related to education, gender, severity of symptoms, medication status, or hemispheric dominance for perceiving dichotic words. The findings add to growing evidence for the existence of a subgroup of schizophrenia having a specific verbal memory deficit that is not limited to working memory, but extends to learning and recall of verbal material.     

Using intraindividual variability to detect malingering in cognitive performance

The utility of measures for detecting malingering was evaluated using a simulation design in which half the participants were encouraged to do their best and half were asked to feign head injury. Particular attention was focused on the utility of repeated assessment (intraindividual variability) in discriminating the groups. Participants were tested on three occasions on measures commonly used to detect malingering including a specific symptom validity test (SVT). The results indicated that multiple measures of malingering obtained in single assessment (occasion one) discriminated the groups effectively. In addition, however, intraindividual variability in performance, particularly of indicators from the SVT, provided unique information beyond level of performance. The results suggest that response inconsistency across testing sessions may be a clinically useful measure for the detection of malingering.     

A novel multidomain computerized cognitive assessment for attention-deficit hyperactivity disorder: evidence for widespread and circumscribed cognitive deficits

Multidomain assessment may enhance the diagnosis of cognitive impairment in children with attention-deficit hyperactivity disorder (ADHD). A set of novel Web-enabled computerized tests has recently been shown to be valid for identifying mild cognitive impairment and characterizing the cognitive profile associated with various disorders. It was anticipated that these tests would be well suited for use in children with ADHD. The authors tested this idea in a pilot study of 15 children (12 males, 3 females; mean age, 11 years 10 months; range, 9-15 years) with ADHD and 15 age-, education-, and gender-matched controls. The profile of cognitive impairment in ADHD children off methylphenidate across 6 cognitive domains (memory, executive function, visual-spatial skills, verbal function, attention, and motor skills) was described relative to controls. The effect of treatment with methylphenidate was examined by comparing the ADHD children on methylphenidate and on placebo (administered in a double-blind randomized fashion) relative to controls and by comparing the ADHD children on methylphenidate relative to placebo. Significant impairment in ADHD was evident in memory, visual-spatial, verbal, and attention domains, and near-significant impairment was observed in executive function and motor skills. On methylphenidate but not placebo, performance was comparable to controls in immediate verbal memory, psychomotor accuracy, visual-spatial, verbal rhyming, and overall battery performance. Significant improvement with administration of methylphenidate relative to placebo was evident for psychomotor accuracy, verbal rhyming, and overall battery performance. Hence, on the limited basis of this pilot study, the set of computerized tests studied appears to be useful for measuring cognitive function in ADHD; however, additional studies are needed to confirm this.     

Interpreting clinical evidence of malingering: a Bayesian perspective

Customary ways of reporting on or testifying about malingering have shortcomings. Stating an opinion "with reasonable medical certainty" tells fact-finders little about how much confidence the opinion deserves; stating that an individual's behavior is similar to that of known malingerers does not convey the information that fact-finders really need to know, which is the likelihood that the evaluee in question is a malingerer, given the evaluator's findings. Mossman and Hart (Mossman D, Hart KJ: Presenting evidence of malingering to courts: insights from decision theory. Behav. Sci. Law 14:271-91, 1996) recommend that mental health professionals address this problem by using Bayes' theorem to interpret test data from evaluations. However, these authors do not discuss the use of evidence obtained during interviews and from other clinical contexts, nor do they describe a method for quantifying imprecision in Bayesian probabilities. This article provides examples of how forensic evaluators might use a Bayesian perspective to interpret clinical indicia of malingering observed during evaluations of adjudicatory competence. The article discusses sources of imprecision in Bayesian posterior probabilities, describes a method for characterizing that imprecision using confidence intervals, and then presents several sample calculations that illustrate how interview findings change the likelihood of malingering. The article also discusses the implications of the Bayesian approach for forensic evaluations and for future research on malingered incompetence.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

Schizandrin prevents dexamethasone-induced cognitive deficits

Objective To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schi-zandrin (Sch) against dexamethasone (Dex)-induced neurotoxicity in vivo and in vitro. Methods Cerebral cortical cells from neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9 days, and then treated with Dex (10 -4 , 10 -5 , 10 -6 or 10 -7 mol/L) for 24 h or pretreated with 10 -4 mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Schfor 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I (5 mg/kg·d -1 Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg·d -1 Sch i.g. for 14 days). Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons. Results Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes. Conclusion Sch has neuroprotective effects against insults induced by glucocorticoid.     

Treating the cognitive deficits of schizophrenia

Schizophrenia is characterized by significant cognitive impairments that predict impairment in multiple domains of community outcome. Pharmacologic and psychosocial treatments are available that address these cognitive deficits. There is growing evidence that patients taking second-generation antipsychotic medications perform better on tests of cognitive function than those taking conventional neuroleptics. In addition, there have been a number of medications from other classes being investigated as cognitive enhancers for schizophrenia. Cognitive rehabilitation approaches focus on bypassing, compensating for, or remediating observed impairments in cognitive function. Outcomes for patients have been improved by cognitive remediation, errorless learning, and the use of supportive environments. Combining the newest pharmacologic interventions for cognitive dysfunction with state of the art psychosocial treatments aimed at ameliorating or bypassing deficits is likely to produce the most favorable outcomes for individuals with schizophrenia.     

Remediation of cognitive deficits in schizophrenia

Studies have suggested that schizophrenia is characterized by an impairment in the dorsolateral prefrontal cortex that prevents learning of some elementary information processing tasks. To test this hypothesis, the authors administered the Wisconsin Card Sorting Test to 16 schizophrenic inpatients with standard instructions and either contingent or noncontingent reinforcement. Performance was markedly impaired under each condition. A second cohort (N = 12) was tested after receiving instructions plus rehearsal and feedback. These subjects' performance was comparable to nonpatient norms and was maintained on a subsequent day. The results indicate that deficits in performance on the Wisconsin Card Sorting Test are remediable, whether or not they are due to neurological impairment.     

Predicting financial deficits from a standard neuropsychological assessment: preliminary evidence in mild cognitive impairment

Neurological Sciences - Patients with mild cognitive impairment (MCI) might experience difficulties in numerical and financial abilities of daily living that compromise their autonomy. The aim of...     

Gender-related cognitive deficits in Alzheimer's disease

Recent studies have identified cognitive deficits in semantic memory and verbal language abilities among women with Alzheimer's disease (AD). Few studies to date have explored gender differences in episodic memory function in AD. The present study compared the performance of men and women diagnosed with AD on a battery of neuropsychological measures. Results indicated the presence of gender-related cognitive deficits on tasks of confrontation naming, expressive word knowledge, and both episodic and semantic memory for women with AD, relative to findings in men.     

Cholinergic-dependent cognitive deficits in Parkinson's disease

In a double-blind cross-over study, the effects of a subthreshold dose of scopolamine (0.25 mg) on memory were compared in 32 control subjects and 32 parkinsonian patients who were without any sign of intellectual and mnemic impairment. Although the scores of the controls in the memory test battery showed no deterioration after the administration of scopolamine, the same dose resulted in significantly reduced memory performance in parkinsonian patients in two tests which involved the recognition of meaningless drawings. The selective vulnerability of parkinsonian subjects without cognitive impairment to a subthreshold dose of scopolamine suggests the existence of an underlying alteration of central cholinergic transmission. The neuropsychological findings in our study agree with postmortem biochemical data, which showed decreased cortical choline acetyltransferase activity in all parkinsonian patients, suggesting the existence of neuronal compensation in parkinsonian patients who are without cognitive impairment.     

Subtle cognitive deficits after cerebellar infarcts

The role of the cerebellum in cognitive functions has been under debate. We investigated the neuropsychological functioning of patients with cerebellar lesions (infarcts) and evaluated the significance of laterality in cognitive symptoms. Twenty-six patients with exclusive cerebellar lesions as verified by clinical and neuroradiological findings underwent a neuropsychological assessment at the acute stage and at 3 months. Their performance was compared with 14 controls, also assessed twice. The focus was on four domains: visuospatial/motor functions, episodic memory, working memory and attentional shifting/execution. Both groups improved over time. Statistical differences emerged in tests in the visuomotor domain as well as in the episodic and working memory domains. Patients with left cerebellar lesion were slow in a visuospatial task, whereas those with right cerebellar lesions had verbal memory difficulty compared with controls. By 3 months, 77% of the patients had returned to work, and only one had cognitive impairment and did not return to work. Our results indicate that cerebellar infarcts may result in subtle cognitive changes perhaps primarily related to working memory deficit. The symptoms may be mediated by the contralateral cortical hemisphere, left cerebellar infarcts producing mild right hemispheral dysfunction and right cerebellar infarct producing mild left hemispheral dysfunction.     

Focal cognitive deficits accentuated by depression

A patient with a postoperative posterior right hemisphere lesion underwent neuropsychological testing during a major depressive episode, and again following remission of the depression. Qualitative visuoconstructive deficits typical of right hemisphere damage were present when the patient was depressed, but were absent following treatment of the depression. Verbal intelligence, cooperation, and vigilance were normal. The case suggests that depression may accentuate focal cognitive signs of fixed lesions in the absence of global impairment of function.