Search

Liability to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published GWAS in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“Concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants demonstrating the counterintuitive (“Discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education and/or schizophrenia at p−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs, and many of these have been validated by larger, more recent single-phenotype GWAS. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms: early neurodevelopmental pathways that characterize concordant allelic variation, and adulthood synaptic pruning pathways that were linked to the paradoxical positive genetic association between education and schizophrenia. Further, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia, but also to the broader biological dimensions that are implicated in both general health outcomes and psychiatric illness.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Background: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WMH) burden. We examined whether inflammatory/endothelial dysfunction biomarkers are associated with cognition after SVS in AAs. Methods: Biomarkers were obtained in 24 subjects (median age 56.5 years, 54% women, median 12 years education). Cognition was assessed more than 6 weeks poststroke using the memory composite score (MCS), which was generated using recall from the Hopkins Verbal Learning Test-II and Brief Visuospatial Memory Test-Revised. A semi-automated, volumetric protocol was used to quantify WMH volume (WMHv) on clinical MRI scans. Potential biomarkers including vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, interferon gamma, and thrombin-antithrombin (TAT) were log-transformed and correlated with MCS with adjustment for potential confounders. Results: Among serum biomarkers, only VCAM-1-correlated with poorer memory based on the MCS (r = −.659; P = .0006). VCAM-1 (r = .554; P = .005) and age (r = .479; P = .018) correlated with WMHv; VCAM-1 was independently associated with MCS after adjustment for WMHv, age, and education (P = .023). Conclusions: The findings of this exploratory analysis suggest that endothelial dysfunction and inflammation as reflected by VCAM-1 levels may play a role in poststroke cognitive impairment. Additional studies are needed to validate this observation and to evaluate this relationship in non-AAs and with other stroke types and compare this finding to cognitive impairment in nonstroke populations.

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function wereSGCZ,ATXN1,MAPT,AUTS2, andP2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.

Objective: To evaluate the safety and efficacy of a novel solid-state, caloric vestibular stimulation (CVS) device to provide adjuvant therapy for the prevention of episodic migraine in adult migraineurs. Background: Migraine causes significant disability in ~12% of the world population. No current migraine preventive treatment provides full clinical relief, and many exhibit high rates of discontinuation due to adverse events. Thus, new therapeutic options are needed. CVS may be an effective and safe adjuvant-therapy for the prevention of episodic migraine.\ud \ud Methods: In a multicenter, parallel-arm, block-randomized, placebo-controlled clinical trial (clinicaltrials.gov: NCT01899040), subjects completed a 3-month treatment with the TNMTM device for CVS (refer to Figure 2 for patient enrollment and allocation). The primary endpoint was the change in monthly migraine days from baseline to the third treatment month. Secondary endpoints were 50% responder rates, change in prescription analgesic usage and difference in total subjective headache-related pain scores. Device safety assessments included evaluation of any impact on mood, cognition or balance. \ud \ud Results: Per-protocol, active-arm subjects showed immediate and steady declines in migraine frequency over the treatment period. After three months of treatment, active-arm subjects exhibited significantly fewer migraine days (-3.8 ± 0.5 from a baseline burden of 7.7 ± 0.5 migraine days). These improvements were significantly greater than those observed in control subjects (-1.1 ± 0.6 from a baseline burden = 6.9 ± 0.7 migraine days) and represented a therapeutic gain of -2.7 migraine days, CI = -0.9 to -4.7, p = 0.012. Active arm subjects also reported greater reductions in acute medication usage and monthly pain scores compared to controls. No adverse effects on mood, cognition or balance were reported. Subjects completed the trial with an average rate of 90% treatment adherence. No serious or unexpected adverse events were recorded. The rate of expected adverse events was similar across the active and the placebo groups, and evaluation confirmed that subject blinding remained intact.\ud \ud Conclusion: The TNM device for CVS appears to provide a clinically efficacious and highly tolerable adjuvant therapy for the prevention of episodic migraine.

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is frequently used in research protocols and increasingly in clinical practice. Despite the frequency of its use, important aspects of its measurement validity have yet to be established in healthy adults. Two hundred and fifty-five individuals completed the CANTAB and traditional neuropsychological tests commonly used in clinical practice, including selected subtests from the Wechsler Adult Intelligence Scale, Controlled Oral Word Association Test, Animal Naming, Trail Making Tests A and B, the Stroop test, and the Green Story Recall test. Results showed that CANTAB subtests were modestly correlated with traditional subtests. Correlations between CANTAB subtests and traditional subtests were less consistent when age and education were controlled for. In conclusion, the CANTAB shows modest associations with traditional neuropsychological test measures.

Correction to: Molecular Psychiatry (2017) 22, 336–345; doi:10.1038/mp.2016.244;published online 17 January 2017 Data access for several cohorts used in this study was provided by the National Center for Biotechnology Information (NCBI) database of Genotypes and Phenotypes (dbGaP). dbGaP accession numbers for these cohorts were as follows

Topiramate is an antiepileptic drug that has marked treatment-limiting side effects on specific aspects of cognitive performance in both patients and healthy volunteers. Because these severe side effects occur only in certain individuals, identifying genetic or environmental variables that influence cognitive response would be of great utility in determining whether to administer this drug to a patient. We gave an acute 100 mg oral dose of topiramate to 158 healthy volunteers and measured how the drug changed their performance on a diverse battery of cognitive tests. We found a wide range of responses to topiramate, and we demonstrated that not all tests in the battery were equally affected. There was no correlation between the effect of topiramate and either education level or baseline cognitive performance. Of interest, there was an up to 55-fold variation in the topiramate plasma levels of the participants. Our genome-wide association study (GWAS) of cognitive response did not reveal any genome-wide significant associations; the study was powered to find variants explaining at least 25% of the variation in cognitive response. Combining the results of this GWAS with a retrospective study of cognitive complaints in 290 epilepsy patients who received topiramate as part of their treatment also did not result in a significant association. Our results support the need for additional genetic studies of topiramate that use larger sample sizes.

Clinicians routinely query factors known to impact cognitive test scores, including age and education. However, without data delineating the impact of less-frequently tracked variables, clinicians are limited to educated inferences about their effect. We explored the relationship of demographics, pastimes, and strategies with cognitive scores in a sample of 499 healthy young volunteers. As expected, age, education, ethnicity, and native language were strongly associated with most tests, while gender and dysphoria were associated with only some. Interestingly, pastimes such as playing number games and word games, and doing activities similar to the tests, were strongly associated with many measures, and testing strategies with almost all. Importantly, at least an additional 50% of the variation in Digit Span Backward and Animals scores was explained by adding covariates about pastimes and strategies to demographic covariates. These results support the utility of querying these elements.

The 2008 Diversity Summit recognized the many advantages of increasing the number of neuropsychologists from ethnically diverse backgrounds. The Summit addressed the aspiration of creating a more ethnically diverse body of neuropsychologists by increasing the recruitment of ethnic minority students to neuropsychology training programs. Challenges to successful recruitment and retention of ethnic minority students were discussion points at the Summit. This paper summarizes and expands these points and also suggests solutions to these challenges with the aim of stimulating innovative approaches to increasing the representation of ethnic minorities in neuropsychology.

These proceedings document the Multicultural Problem Solving Summit, which was held in Waikoloa Village, Hawaii in February 2008. Welcoming comments were followed by a brief review of the history o...

Postoperative delirium is associated with increased morbidity and mortality. Preexisting cognitive impairment and depression have been frequently cited as important risk factors for this complication. This prospective cohort study was designed to determine whether individuals who perform poorly on preoperative cognitive tests and/or exhibited depressive symptoms would be at high risk for the development of postoperative delirium.One hundred nondemented patients, aged 50 yr and older, scheduled to undergo major, elective noncardiac surgery completed a preoperative test battery that included measures of global cognition, executive function, and symptoms of depression. Known preoperative risk factors for delirium were collected and examined with the results of the preoperative test battery to determine the independent predictors of delirium.The overall incidence of delirium was 16% and was associated with increased hospital duration of stay (P0.05) and an increased incidence of postoperative complications (P0.01). Delirious subjects did not differ from their nondelirious cohorts with regard to their preoperative global cognitive function, preexisting medical comorbidities, age, anesthetic management, or history of alcohol use. Preoperative executive scores (P0.001) and depression (P0.001), as measured by the Trail Making B test and Geriatric Depression Scale-Short Form, respectively, were found to be independent predictors of postoperative delirium.Low preoperative executive scores and depressive symptoms independently predict postoperative delirium in older individuals. A rapid, simple test combination including tests of executive function and depression could improve physicians' ability to recognize patients who might benefit from a perioperative intervention strategy to prevent postoperative delirium.

While the application of normative standards is vital to the practice of clinical neuropsychology, data regarding normative change remains scarce despite the frequency of serial assessments. Based on 285 normal individuals, we provide co-normed baseline data with demographic adjustments and test-retest standardized regression based (SRB) models for three time points for several measures. These models delineate normal, expected change across time, and yield standardized z-scores that are comparable across tests. Using a new approach, performance on any previous trial was accounted for in the subsequent models of change, yielding serial normative formulas that model change trajectories rather than simple change from point to point. These equations provide indices of deviation from expected baseline and change for use in clinical or research settings.

Objective Previous studies have shown that elevated depressive symptoms are associated with increased risk of postoperative delirium. However, to our knowledge no previous studies have examined whether different components of depression are differentially predictive of postoperative delirium. Methods One thousand twenty patients were screened for postoperative delirium using the Confusion Assessment Method and through retrospective chart review. Patients underwent cognitive, psychosocial, and medical assessments preoperatively. Depression was assessed using the Geriatric Depression Scale–Short Form. Results Thirty-eight patients developed delirium (3.7%). Using a factor structure previously validated among geriatric medical patients, the authors examined three components of depression as predictors of postoperative delirium: negative affect, cognitive distress, and behavioral inactivity. In multivariate analyses controlling for age, education, comorbidities, and cognitive function, the authors found that greater behavioral inactivity was associated with increased risk of delirium (OR: 1.95 [1.11, 3.42]), whereas negative affect (OR: 0.65 [0.31, 1.36]) and cognitive distress (OR: 0.95 [0.63, 1.43]) were not. Conclusion Different components of depression are differentially predictive of postoperative delirium among adults undergoing noncardiac surgery.

Since its identification, the dinoflagellate Pfiesteria piscicida has been implicated in fish kills and fish disease in the southeastern United States. Adverse health effects have been reported in researchers working with the organism and in watermen following exposure to a fish kill in Maryland. A bioactive secretion is postulated as the cause of these effects but has not yet been isolated and chemically characterized. The biology and toxicology of this organism remain the topic of debate and research.

Introduction A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset. Objective To explore the effects of the polymorphic polyT tract (rs10524523, referred as ‘523') on cognitive performance in cognitively healthy elderly individuals. Methods One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 ‘523' (S, L, VL) and the apolipoprotein E ( APOE ) (ɛ2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on ‘523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the ‘523' genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ɛ4 status. A planned subanalysis was undertaken to evaluate the association between ‘523' genotypes and test performance in a sample restricted to APOE ɛ3 homozygotes. Results The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ɛ3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing. Conclusions Results suggest important APOE -independent associations between the TOMM40 ‘523' polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer's disease.

Serial assessments are now common in neuropsychological practice, and have a recognized value in numerous clinical and forensic settings. These assessments can aid in differential diagnosis, tracking neuropsychological strengths and weaknesses over time, and managing various neurologic and psychiatric conditions. This document provides a discussion of the benefits and challenges of serial neuropsychological testing in the context of clinical and forensic assessments. Recommendations regarding the use of repeated testing in neuropsychological practice are provided.

One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genome-wide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining >4-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes.

Objective To characterize the effects of critical illness in the daily lives and functioning of acute respiratory distress syndrome survivors. Survivors of acute respiratory distress syndrome, a systemic critical illness, often report poor quality of life based on responses to standardized questionnaires. However, the experiences of acute respiratory distress syndrome survivors have not been reported. Design We conducted semistructured interviews with 23 acute respiratory distress syndrome survivors and 24 caregivers 3 to 9 mos after intensive care unit admission, stopping enrollment after thematic saturation was reached. Transcripts were analyzed, using Colaizzi's qualitative methodology, to identify significant ways in which survivors' critical illness experience impacted their lives. Setting Medical and surgical intensive care units of an academic medical center and a community hospital. Patients We recruited consecutively 31 acute respiratory distress syndrome survivors and their informal caregivers. Eight patients died before completing interviews. Interventions None. Measurements and main results Participants related five key elements of experience as survivors of acute respiratory distress syndrome: 1) pervasive memories of critical care; 2) day-to-day impact of new disability; 3) critical illness defining the sense of self; 4) relationship strain and change; and 5) ability to cope with disability. Survivors described remarkable disability that persisted for months. Caregivers' interviews revealed substantial strain from caregiving responsibilities as well as frequent symptom minimization by patients. Conclusions The diverse and unique experiences of acute respiratory distress syndrome survivors reflect the global impact of severe critical illness. We have identified symptom domains important to acute respiratory distress syndrome patients who are not well represented in existing health outcomes measures. These insights may aid the development of targeted interventions to enhance recovery and return of function after acute respiratory distress syndrome.

We can only benefit from raising public awareness about the unique role of clinical neuropsychology in patient care and clinical research. Public awareness of the distinctive skills of our practitioners and researchers and the utility of our products may well be linked to our viability as a field given the current healthcare and funding climates. This article discusses the goals of public awareness efforts for clinical neuropsychology, and outlines current resources that can be utilized toward this end. We review the process of creating new public awareness resources and discuss ideas for how practitioners can become involved public awareness efforts. We consider some of the many issues driving the need for public awareness activities and resources, highlight the need for practitioners and professional organizations to be self-advocates, and hope to inspire our field to the very feasible process of integrating public awareness efforts into professional practice.

Postoperative delirium has been associated with greater complications, medical cost, and increased mortality during hospitalization. Recent evidence suggests that preoperative executive dysfunction and depression may predict postoperative delirium; however, the combined effect of these risk factors remains unknown. This study examined the association among preoperative executive function, depressive symptoms, and established clinical predictors of postoperative delirium among 998 consecutive patients undergoing major noncardiac surgery.A total of 998 patients were screened for postoperative delirium (n = 998) using the Confusion Assessment Method as well as through retrospective chart review. Patients underwent cognitive, psychosocial, and medical assessments preoperatively. Executive function was assessed using the Concept Shifting Task, Letter-Digit Coding, and a modified Stroop Color Word Interference Test. Depression was assessed by the Beck Depression Inventory.Preoperative executive dysfunction (P = 0.007) and greater levels of depressive symptoms (P = 0.049) were associated with a greater incidence of postoperative delirium, independent of other risk factors. Secondary analyses of cognitive performance demonstrated that the Stroop Color Word Interference Test, the executive task with the greatest complexity in this battery, was more strongly associated with postoperative delirium than simpler tests of executive function. Furthermore, patients exhibiting both executive dysfunction and clinically significant levels of depression were at greatest risk for developing delirium postoperatively.Preoperative executive dysfunction and depressive symptoms are predictive of postoperative delirium among noncardiac surgical patients. Executive tasks with greater complexity are more strongly associated with postoperative delirium relative to tests of basic sequencing.

Depression is often associated with neurocognitive deficits in older adults, particularly in the domains of information processing speed, episodic memory, and executive functions. Greater neurocognitive dysfunction while depressed is associated with a less effective treatment response; however, questions remain about the specific variables that characterize patients showing low treatment response and persistent cognitive deficiencies. Objectives The authors examined neurocognitive variables that differentiated patients who showed robust versus weak responses to antidepressant therapy. Participants The baseline sample included 110 women and 67 men, with a mean age of 69.1 years (SD = 6.9) and mean education of 14 years (SD = 3.3). Design Patients enrolled in a treatment study completed both a structured diagnostic assessment for depression and neuropsychological testing at study entry and 1-year follow-up. Measurements Clinicians rated patient depression using the Montgomery-Asberg Depression Rating Scale. Neuropsychological assessments consisted of prose recall and percent retention (Wechsler Memory Scale -III Logical Memory), word-list recall, attention and visuomotor processing speed (Trail Making A, Symbol Digit Modalities Test), and mental flexibility (Trail Making B). Interventions Patients underwent treatment for depression following the guidelines of the Duke Somatic Treatment Algorithm for Geriatric Depression approach. Results Individuals who demonstrated the greatest improvement in mood symptoms at follow-up exhibited better prose recall and faster processing speed at baseline than individuals who demonstrated weaker treatment responses. These differences remained after controlling for depression severity at both time-points. Conclusion The current results suggest that better pretreatment cognitive function, particularly in verbal memory, is associated with a greater treatment response in late-life depression.

Background Depression is highly prevalent in patients before surgery, and it has been widely shown to have a serious impact on their postoperative outcomes. It would therefore be desirable for physicians to obtain a quick, simple screen to evaluate depression to consider treatment of symptomatology and potentially optimize postoperative outcomes. Methods In this study, we investigated the prevalence of depression in a presurgical inpatient sample undergoing major, noncardiac surgery. In addition, we sought to establish the Geriatric Depression Scale-Short Form (GDS-SF) as a valid screening tool for depression by examining its relationship to the Beck Depression inventory (BDI) by age and gender. Results In our sample of 1043 presurgical candidates, prevalence of depression as established by the BDI was significantly higher than rates consistently found in healthy community samples. Depression was more common in women than in men (P = 0.02), and depression rates were lower in elders relative to middle-aged and younger groups (P = 0.003 and 0.003, respectively). In addition, we found that there was a high correlation between the BDI and the GDS-SF within each of the age groups. Conclusions These data further support the need for depression screens in presurgical populations and establish the validity of the GDS-SF as a valid quick assessment alternative available to physicians.

It was recently suggested that the Kibra polymorphism rs17070145 has a strong effect on multiple episodic memory tasks in humans. We attempted to replicate this using two cohorts of European genetic origin (n = 319 and n = 365). We found no association with either the original SNP or a set of tagging SNPs in the Kibra gene with multiple verbal memory tasks, including one that was an exact replication (Auditory Verbal Learning Task, AVLT). These results suggest that Kibra does not have a strong and general effect on human memory.

The views expressed in this document are those of Division 40. They have not been approved by the governing body of APA and should not be construed as representing the policy of APA as a whole or o...

Neuropsychological assessment plays an important part in the differential diagnosis of dementing disorders, particularly in clinically ambiguous situations (e.g., suspected early dementia) and in the context of confounding factors, such as the presence of a superimposed depression or advanced age (1,2). Within the medical evaluation of dementia, the neuropsychological evaluation provides unique information in the form of a “behavioral sample” that can be used to determine in an objective, quantifiable manner the presence of cognitive symptoms and their functional significance. To accomplish these basic aims, the neuropsychological examination employs rigorous, standardized psychometric tests of memory and cognitive function and relies heavily on the application of normative standards and on a fundamental understanding of brain function. The examination results in metric values for discrete cognitive and behavioral capacities, which can then be used by the examining clinician to arrive at diagnostic inferences, to make judgments of functional abilities, and to establish a benchmark for monitoring future change and responsiveness to medical treatments and therapies. With advances in both public awareness of dementia and greater availability of symptomatic treatments for Alzheimer’s disease (AD), there is an increasing tendency for patients to present to their primary care physicians with mild complaints of memory loss and cognitive disturbance (3,4). Disentangling what may be normal cognitive change from the pre-clinical stages of dementia is a daunting task and one that is not easily remedied with a quick bedside examination of mental status (5). In these situations, more detailed and sensitive assessment of function is needed, particularly if the complaint is persistent. The goal of this chapter is to provide a comprehensive discussion of the role of neuropsychological assessment in the context of the dementia evaluation. The chapter is divided into three sections with the broad aim of assisting medical professionals, neurologists, and other physicians in understanding the fundamentals of the neuropsychological examination of dementia. The first section focuses on the clinical utility of neuropsychological testing and addresses what the assessment entails. The second section turns to a discussion of how the test results are clinically interpreted, the use

Correction to: European Journal of Human Genetics advance online publication, 3 February 2010; doi:10.1038/ejhg.2010.2