•Social cognitive deficits are present in a wide range of clinical conditions.•These are comparable in magnitude to more established neurocognitive deficits.•Social cognitive deficits appear to hold ...both functional and clinical relevance.•These are an important but frequently overlooked aspect of cognitive dysfunction.
Social cognition includes a range of cognitive processes that help individuals to understand how others think and feel. There is emerging evidence that social cognitive deficits may represent a transdiagnostic issue, potentially serving as a marker of neurological abnormality. We performed an electronic database search in order to identify published, peer-reviewed meta-analyses that compared facial emotion recognition or theory of mind task performance between individuals meeting clinical criteria for a psychiatric, neurological or developmental condition against healthy controls. We identified 31 meta-analyses eligible for inclusion that examined performance across relevant tasks among 30 different clinical populations. The results suggest that social cognitive deficits appear to be a core cognitive phenotype of many clinical conditions. Across the clinical groups, deficits in social cognitive domains were broadly similar in magnitude to those previously reported for more established aspects of cognition, such as memory and executive function. There is a need to clarify the ‘real world’ impact of these deficits, and to develop effective transdiagnostic interventions for those individuals that are adversely affected.
Abstract Objective A premorbid IQ deficit supports a developmental dimension to schizophrenia and its cognitive aspects that are crucial to functional outcome. Better characterisation of the ...association between premorbid IQ and the disorder may provide further insight into its origin and etiology. We aimed to quantify premorbid cognitive function in schizophrenia through systematic review and meta-analysis of longitudinal, population-based studies, and to characterize the risk of schizophrenia across the entire range of premorbid IQ. Method Electronic and manual searches identified general population-based cohort or nested case–control studies that measured intelligence before onset of schizophrenic psychosis using standard psychometric tests, and that defined cases using contemporaneous ICD or DSM. Meta-analyses explored dose–response relationships between premorbid cognitive deficit (using full-scale, verbal and performance IQ) and risk of schizophrenia. Meta-regression analyses explored relationships with age of illness onset, change in premorbid intelligence over time and gender differences. Results Meta-analysis of 4396 cases and over 745 000 controls from 12 independent studies confirmed significant decrements in premorbid IQ (effect size − 0.43) among future cases. Risk of schizophrenia operated as a consistent dose–response effect, increasing by 3.7% for every point decrease in IQ (p < 0.0001). Verbal and nonverbal measures were equally affected. Greater premorbid IQ decrement was associated with earlier illness onset (p < 0.0001). There was no evidence of a progressively increasing deficit during the premorbid period toward illness onset. Conclusions Strong associations between premorbid IQ and risk for schizophrenia, and age of illness onset argue for a widespread neurodevelopmental contribution to schizophrenia that operates across the entire range of intellectual ability. This also suggests higher IQ may be protective in schizophrenia, perhaps by increasing active cognitive reserve.
Background Cognitive endophenotypes may further our understanding of the genetic basis of psychiatric disorders, and the catechol- O -methyltransferase ( COMT ) gene is a promising candidate gene for ...both cognitive function and disorder. We conducted a meta-analysis of reported associations between the COMT Val158/108Met polymorphism and measures of memory and executive function. Methods The PubMed database was searched for studies relating cognitive functions and the COMT Val158/108Met polymorphism. This enabled meta-analyses of six cognitive phenotypes (Trail Making task, verbal recall, verbal fluency, IQ score, n-back task, and Wisconsin Card Sorting Test). Data were extracted by two reviewers and included cognitive scores by COMT genotype, publication year, diagnostic status, ancestry, proportion of male participants, and whether genotype frequencies were consistent with Hardy-Weinberg equilibrium. Results We found no association between COMT genotype and the majority of phenotypes. There was evidence of association with IQ score ( d = .06), which did not differ significantly by ancestry, sex, average sample age, or patient status. For the n-back task, there was no robust evidence for genetic association, but the effect size was significantly larger in patient ( d = .40) than nonpatient ( d = −.27) populations, larger in both samples with fewer male subjects, and those of greater average age. There was also evidence of publication bias and decreasing effect sizes with later publication. Conclusions Despite initially promising results, the COMT Val158/108Met polymorphism appears to have little if any association with cognitive function. Publication bias may hamper attempts to understand the genetic basis of psychological functions and psychiatric disorders.
Computerized assessments are already used to derive accurate and reliable measures of cognitive function. Web-based cognitive assessment could improve the accessibility and flexibility of research ...and clinical assessment, widen participation, and promote research recruitment while simultaneously reducing costs. However, differences in context may influence task performance.
This study aims to determine the comparability of an unsupervised, web-based administration of the Cambridge Neuropsychological Test Automated Battery (CANTAB) against a typical in-person lab-based assessment, using a within-subjects counterbalanced design. The study aims to test (1) reliability, quantifying the relationship between measurements across settings using correlational approaches; (2) equivalence, the extent to which test results in different settings produce similar overall results; and (3) agreement, by quantifying acceptable limits to bias and differences between measurement environments.
A total of 51 healthy adults (32 women and 19 men; mean age 36.8, SD 15.6 years) completed 2 testing sessions, which were completed on average 1 week apart (SD 4.5 days). Assessments included equivalent tests of emotion recognition (emotion recognition task ERT), visual recognition (pattern recognition memory PRM), episodic memory (paired associate learning PAL), working memory and spatial planning (spatial working memory SWM and one touch stockings of Cambridge), and sustained attention (rapid visual information processing RVP). Participants were randomly allocated to one of the two groups, either assessed in-person in the laboratory first (n=33) or with unsupervised web-based assessments on their personal computing systems first (n=18). Performance indices (errors, correct trials, and response sensitivity) and median reaction times were extracted. Intraclass and bivariate correlations examined intersetting reliability, linear mixed models and Bayesian paired sample t tests tested for equivalence, and Bland-Altman plots examined agreement.
Intraclass correlation (ICC) coefficients ranged from ρ=0.23-0.67, with high correlations in 3 performance indices (from PAL, SWM, and RVP tasks; ρ≥0.60). High ICC values were also seen for reaction time measures from 2 tasks (PRM and ERT tasks; ρ≥0.60). However, reaction times were slower during web-based assessments, which undermined both equivalence and agreement for reaction time measures. Performance indices did not differ between assessment settings and generally showed satisfactory agreement.
Our findings support the comparability of CANTAB performance indices (errors, correct trials, and response sensitivity) in unsupervised, web-based assessments with in-person and laboratory tests. Reaction times are not as easily translatable from in-person to web-based testing, likely due to variations in computer hardware. The results underline the importance of examining more than one index to ascertain comparability, as high correlations can present in the context of systematic differences, which are a product of differences between measurement environments. Further work is now needed to examine web-based assessments in clinical populations and in larger samples to improve sensitivity for detecting subtler differences between test settings.
•Inflammation in the brain occurs in many CNS disorders (e.g., Alzheimer’s disease).•No effective neuroinflammatory treatments currently exist.•POCD may serve as an approach to rapidly demonstrate ...drug efficacy.•Demonstration of efficacy for novel brain-penetrant anti-inflammatories is warranted.
Inflammation within the central nervous system (CNS; neuroinflammation) is a major contributor to lasting symptoms of traumatic brain injury and stroke, and likely has a casual role Alzheimer’s disease (AD) and other neurodegenerative conditions. Therapeutic modulation of the immune processes that initiate and maintain neuroinflammation is of growing scientific interest but neuroinflammatory drug development is hampered by limited reliability and availability of neuroimaging or other biomarkers in humans. Better means of establishing drug efficacy on human neuroinflammation would have great value in accelerating the development of neuroinflammatory compounds for many clinical indications. Here, we discuss the use of postoperative cognitive decline (POCD), which is hypothesised to have a neuroinflammatory basis, as an acute indication to demonstrate the efficacy of novel neuroinflammatory drugs.
Intervention and treatment in Alzheimer's disease dementia (AD-dementia) can be cost effective but the majority of patients are not diagnosed in a timely manner. Technology is now available that can ...enable the earlier detection of cognitive loss associated with incipient dementia, offering the potential for earlier intervention in the UK health care system. This study aimed to determine to what extent the timing of an intervention affects its cost-effectiveness.
Using published data describing cognitive decline in the years prior to an AD diagnosis, we modelled the effects on healthcare costs and quality-adjusted life years of hypothetical symptomatic and disease-modifying interventions. Early and standard interventions were assumed to have equal clinical effects, but the early intervention could be applied up to eight years prior to standard diagnosis.
A symptomatic treatment which immediately improved cognition by one MMSE point and reduced in efficacy over three years, would produce a maximum net benefit when applied at the earliest timepoint considered, i.e. eight years prior to standard diagnosis. In this scenario, the net benefit was reduced by around 17% for every year that intervention was delayed. In contrast, for a disease-modifying intervention which halted cognitive decline for one year, economic benefits would peak when treatment effects were applied two years prior to standard diagnosis. In these models, the maximum net benefit of the disease modifying intervention was fifteen times larger than that of the symptomatic treatment.
Timeliness of intervention is likely to have an important impact on the cost-effectiveness of both current and future treatments. Healthcare policy should aim to optimise the timing of AD-dementia diagnosis, which is likely to necessitate detecting and treating patients several years prior to current clinical practice.
Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic ...medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.
The ability of remote research tools to collect granular, high-frequency data on symptoms and digital biomarkers is an important strength because it circumvents many limitations of traditional ...clinical trials and improves the ability to capture clinically relevant data. This approach allows researchers to capture more robust baselines and derive novel phenotypes for improved precision in diagnosis and accuracy in outcomes. The process for developing these tools however is complex because data need to be collected at a frequency that is meaningful but not burdensome for the participant or patient. Furthermore, traditional techniques, which rely on fixed conditions to validate assessments, may be inappropriate for validating tools that are designed to capture data under flexible conditions. This paper discusses the process for determining whether a digital assessment is suitable for remote research and offers suggestions on how to validate these novel tools.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition associated with cognitive dysfunction. The Cambridge Neuropsychological Test Automated Battery is a computerized set of tests ...that has been widely used in ADHD and in translation/back-translation. Following a survey of translational research relevant to ADHD in experimental animals, a comprehensive literature review was conducted of studies that had used core Cambridge Neuropsychological Test Automated Battery tests 1) to evaluate cognitive dysfunction in ADHD and 2) to evaluate effects of salient drugs in patients and in volunteers. Meta-analysis was conducted where four or more independent datasets were available. Meta-analysis revealed medium-large decrements in ADHD for response inhibition (d = .790, p < .001), working memory (d = .883, p < .001), executive planning (d = .491, p < .001), and a small decrement in attentional set shifting (d = .160, p = .040). Qualitative review of the literature showed some consistent patterns. In ADHD, methylphenidate improved working memory, modafinil improved planning, and methylphenidate, modafinil, and atomoxetine improved inhibition. Meta-analysis of modafinil healthy volunteer studies showed no effects on sustained attention or set shifting. Results were paralleled by findings in experimental animals on comparable tests, enabling further analysis of drug mechanisms. Substantial cognitive deficits are present in ADHD, which can be remediated somewhat with current medications and which can readily be modeled in experimental animals using back-translational methodology. The findings suggest overlapping but also distinct early cognitive effects of ADHD medications and have important implications for understanding the pathophysiology of ADHD and for future trials.
Light and moderate alcohol use has been reported to be associated with both impaired and enhanced cognition. The purpose of this study was to explore whether there was a linear relationship between ...visual memory and alcohol consumption in males and females in a large middle-aged birth cohort population in cross-sectional and longitudinal settings. Data were collected from 5585 participants completing 31-year (1997-1998) and 46-year (2012-2014) follow-ups including Paired Associate Learning (PAL) test at 46-years follow-up. The participants were originally from 12,231 study population of the Northern Finland Birth Cohort 1966 (NFBC1966). The PAL test was conducted to assess visual memory. Reported alcohol use was measured as total daily use of alcohol, beer, wine, and spirits converted into grams and as frequency and amount of use of beer, wine, and spirits. The total daily alcohol use was not associated with reduced visual memory. The frequency of use of beer and wine in males was associated with better visual memory in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal setting. The study suggested a lack of a linear association between drinking and visual memory in the middle-aged population.
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