Spatial Working Memory Strategy Research Articles

Abstract 14714: Long-Term Neurocognitive Safety of LDL-C Lowering With Evolocumab: Open-Label Extension Data From FOURIER

Background: Concerns have been raised about low LDL-C levels and possible adverse effects on cognition. PCSK9 inhibitors markedly lower LDL-C, yet EBBINGHAUS, a prespecified substudy within the FOURIER trial, did not show adverse cognitive changes with evolocumab over 19 months median follow-up. Purpose: To investigate the long-term effects of evolocumab on cognitive function. Methods: EBBINGHAUS was a substudy of cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) within the FOURIER randomized trial of evolocumab vs placebo in patients with established ASCVD. Patients in North America and Europe who completed EBBINGHAUS on study drug were eligible for an open-label extension (OLE) study with evolocumab. The primary endpoint was change in spatial working memory strategy index of executive function score (SWMI) from baseline over time. Secondary endpoints were measures of working memory, episodic memory, and psychomotor speed. A paired t-test was used to compare baseline vs post-baseline scores during OLE. Results: Of 1204 patients from EBBINGHAUS, 306 entered the OLE and were treated with evolocumab for a median of 5.1 years. Median achieved LDL-C was 34 mg/dL (IQR 21-50). No significant change in SWMI occurred during the OLE period overall [mean (±SD) change -0.1±2.7, p=0.73] or when stratified by original randomized allocation ( Figure 1A ). For secondary outcomes, one showed no change during the OLE period, two showed small changes (10-15% of SD), but these were directionally inconsistent (one higher, one lower). In 152 patients originally randomized to evolocumab, there was no significant change in SWMI from randomization through long-term follow-up over a median of 6.7 and a maximum of 7.2 years (mean change 0.1±2.6, p=0.66) ( Figure 1B ). Conclusion: Evolocumab did not lead to any apparent long-term decline in cognitive function through follow-up extending up to 7.2 years.

Stress specifically deteriorates working memory in peripheral neuropathic pain and fibromyalgia.

This study aimed to explore the influence of chronic stress, measured through hair cortisol, on executive functions in individuals with chronic pain. We expected that there would be significant differences in chronic stress and executive functioning between pain patients and healthy controls, as well as between primary and secondary pain classifications. We also hypothesized that hair cortisol concentration was predictive of worse performance on tests of executive functions, controlling for objective and subjective covariates. For this study, 122 participants provided a hair sample (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 58 matched healthy controls). Eighty-four of these participants also completed highly detailed testing of executive functions (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 20 healthy controls). To assess differences in stress levels and executive functions, t-tests were used to compare patients with controls as well as fibromyalgia with peripheral neuropathic pain. Then, univariate regressions were used to explore associations between stress and executive functioning in both chronic pain classifications. Any significant univariate associations were carried over to hierarchical multivariate regression models. We found that patients with chronic pain had significantly higher cortisol levels than healthy controls, but all groups showed similar executive functioning. Hierarchical multiple regression analyses disclosed that in a model controlling for age, sex and pain medication usage, hair cortisol levels explained 8% of the variance in spatial working memory strategy in individuals with chronic pain. The overall model explained 24% of the variance in spatial working memory. In a second model using imputed data, including both objective and subjectively reported covariates, hair cortisol levels explained 9% of the variance, and the full model 31% of the variance in spatial working memory performance. Higher levels of cortisol indicated worse performance. In this study, an applied measure of chronic stress, namely hair cortisol, explained a substantial part of the variance on a spatial working memory task. The current results have important implications for understanding and treating cognitive impairments in chronic pain.

Alirocumab treatment and neurocognitive function according to the CANTAB scale in patients at increased cardiovascular risk: A prospective, randomized, placebo-controlled study

Background and aimsTrials of the fully human monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) alirocumab in hypercholesterolemia demonstrated substantial low-density lipoprotein cholesterol (LDL-C) lowering, reduction in cardiovascular (CV) events and outcomes, and a generally acceptable safety and tolerability profile. The impact of maintaining low LDL-C levels on higher order brain function is unclear, with reports of neurocognitive disorders with other lipid-lowering therapies. MethodsPatients (n = 2176) with heterozygous familial hypercholesterolemia (HeFH) or non-FH, at high or very-high CV risk despite maximally tolerated statin therapy, randomly received subcutaneous alirocumab 75/150 mg or placebo every 2 weeks in this double-blind, placebo-controlled trial. The primary outcome was prospectively evaluated every 24 weeks over 96 weeks by Cambridge Neuropsychological Test Automated Battery (CANTAB). ResultsAmong 2086 patients with CANTAB cognitive domain Spatial Working Memory Strategy (SWMS) assessments, change from baseline to Week 96 in SWMS z-score (primary outcome) achieved noninferiority between alirocumab and placebo (least squares [LS] mean change at Week 96, −0.180 vs −0.200; LS mean difference vs placebo [95% confidence interval]: −0.020 [−0.094 to 0.055], p = 0.6055). Exploratory outcome measures, which further assessed neurocognitive function in the CANTAB domains, did not differ significantly over 96 weeks and achieved nominal noninferiority between treatment groups. Alirocumab resulted in nominally significant reductions in LDL-C and other lipid parameters, and was generally well tolerated. ConclusionsConfirming previous PCSK9 inhibitor data, alirocumab showed no effect on neurocognitive function over 96 weeks’ treatment, substantially reduced LDL-C and was generally well tolerated in patients with HeFH or non-FH at high or very-high CV risk.

Impaired neuropsychological functioning in patients with hypopituitarism.

BackgroundTreatment of pituitary pathology mostly does not result in complete recovery of impairment in cognitive functioning. The primary aim of the current study was to assess cognitive impairment in patients with stable replacement therapy for hypopituitarism during the last 6 months prior to inclusion. It was expected that patients showed subjective and objective subnormal scores on neuropsychological functioning.MethodsForty‐two patients (40% men, 49 ± 15 years) treated for hypopituitarism conducted a neuropsychological test battery, including the Cognitive Failures Questionnaire (CFQ), 15‐Word test (15‐WT), Cambridge Neuropsychological Test Automated Battery (CANTAB) Motor Screening Task (MOT), Spatial Working Memory (SWM) and Affective Go/No‐go (AGN). Results were compared to reference values of healthy norm groups.ResultsMale and female participants scored significantly worse on the CFQ (P < .01, d = 0.91‐4.09) and AGN mean correct latency (P < .01, d = 1.66 and 1.29, respectively). Female participants scored significantly worse on 15‐WT direct recall (P = .01, d = 0.66), 15‐WT delayed recall (P = .01, d = 0.79), SWM total errors (P = .05, d = 0.41), SWM strategy (P = .04, d = 0.43), AGN errors of commission (P = .02, d = 0.56) and omission (P = .04, d = 0.41).ConclusionThis study shows that subjective cognitive functioning is worse in patients treated for hypopituitarism compared to reference data. Also, female participants treated for hypopituitarism score worse on objective aspects of memory and executive functioning compared to reference data. Besides worse focus attention, this objective cognitive impairment was not found in male participants. It is recommended to conduct additional research, which focuses on the design and evaluation of a cognitive remediation therapy, aimed at compensation of impairments in different aspects of memory and executive functioning.

O6.3. ASSOCIATIONS BETWEEN COGNITIVE FUNCTION AND CORTICAL LEVELS OF GLUTAMATE AND GABA IN ANTIPSYCHOTIC-NAïVE PATIENTS WITH SCHIZOPHRENIA OR PSYCHOSIS

BackgroundDysfunctional glutamatergic and gamma-aminobutyric acid (GABA)ergic neurotransmission may be part of the schizophrenia pathophysiology and underlie cognitive deficits. Abnormal levels of glutamate and GABA have been found in patients with first-episode psychosis or schizophrenia, and studies of mainly medicated patients have reported correlations between cortical glutamate and GABA levels and cognitive performance. However, the association between metabolites and cognitive deficits may be altered by treatment. Therefore, we investigated if glutamate and GABA levels in dorsal anterior cingulate cortex were associated with cognitive function in a large group of antipsychotic-naïve patients compared with matched healthy controls and tested the hypothesis that cognitive deficits in patients are related to altered levels of glutamate and GABA.MethodsWe recruited 56 antipsychotic-naïve patients with schizophrenia or psychotic disorder and 51 healthy controls matched for age, sex, and parental education. Magnetic resonance spectroscopy was used to measure glutamate and GABA levels in dorsal anterior cingulate cortex (ACC) on a 3T scanner. The cognitive domains attention (outcome was rapid visual information processing A’ (RVP A’)) and working memory (outcome was spatial working memory (SWM) strategy) were assessed with the Cambridge Neuropsychological Test Automated Battery, and premorbid intelligence estimated with the Danish Adult Reading Test (DART) (outcome was number of words correctly pronounced). A multivariate linear regression model was used to evaluate if levels of glutamate and GABA were different in patients compared with healthy controls, and thereafter to test if glutamate and GABA levels were associated with cognitive performance in the two groups (significant main effect) and if the association differed (significant interaction). SWM strategy score were logarithmically transformed because of non-normality.ResultsLevels of GABA in dorsal ACC were lower in the antipsychotic-naïve patients compared with healthy controls (SCZ: 2.24±0.35; HC: 2.40±0.33, p=0.03), but glutamate levels did not differ significantly between patients and healthy controls (SCZ: 10.75±1.45; HC: 10.91±1.17, p=0.54). Patients performed significantly worse than healthy controls in tests of attention (mean RVP A’ score SCZ: 0.89±0.05; HC: 0.94±0.04, p<0.001) and premorbid IQ (mean DART score SCZ: 17.4±6.5; HC: 21.5±5.3, p=0.001), whereas groups did not differ significantly in SWM strategy score (Median score SCZ: 27.0 (22.0–32.0); HC: 23.0 (19.0–30.0), p=0.18). Higher levels of glutamate were associated with better performance in tests of attention (b=0.01, p=0.016) and SWM (b=-0.02, p=0.008, higher score indicates worse performance) in both patients and healthy controls. The association between cognitive performance and glutamate did not differ significantly between the two groups (both interactions insignificant).There were no significant associations between cognitive function and levels of GABA in dorsal ACC.DiscussionThis is the largest study of antipsychotic-naïve patients to date to investigate the association between cortical glutamate and GABA levels and cognitive function. We found no group differences in levels of glutamate, but lower GABA levels, which indicates reduced GABAergic neurotransmission in dorsal ACC in the pathophysiology of schizophrenia and psychosis.Higher levels of glutamate in dorsal ACC were associated with better cognitive function. However, glutamate levels did not explain the differences in cognitive performance between patients and healthy controls, indicating that other neurotransmitters are important as well.

Cortical thickness, neurocognitive, and body composition effects of fasting during Ramadan.

Background:We aimed to study the anatomical, physiological, and cognitive function of healthy individuals practicing fasting during the month of Ramadan. Measurements were taken 1 week before and 2 weeks after Ramadan fasting.Materials and Methods:Twelve healthy male individuals (mean age ± standard error of the mean: 34.3 ± 2.9 years; body mass index: 26.26 ± 1.4 kg/m2) were assessed for various parameters before and after Ramadan fasting. All the tests were performed in the morning. Body composition characteristics were assessed by bioelectrical impedance analysis using a commercially available body composition analyzer. For neurocognitive analysis, participants underwent the stop signal task (SST), pattern recognition memory task (PRM), and spatial working memory strategy (SWM) from the Cambridge Neuropsychological Test Automated Battery. T1-weighted, 1 mm-thick magnetic resonance images were also acquired.Results:Anthropometric analysis showed a significant decrease in body weight, fat-free mass (FFM), trunk FFM, and trunk predicted muscle mass, while the other body composition parameters did not exhibit any changes. The stop signal reaction time (SSRT) latency (ms) (P > 0.05) and PRM did not show any significant difference before and after fasting. SWM task (P < 0.05) improved significantly after fasting. Cortical thickness data of the whole brain were not significantly different after fasting at any brain location. There was a significant correlation between the left amygdala and the SWM strategy (r2 = 0.518) and between fat and brain segmentation volume (r2 = 0.375).Conclusion:Our pilot data suggest that Ramadan fasting leads to weight loss and FFM reductions and improve cognitive function.

Cognitive Effects of Perioperative Pregabalin: Secondary Exploratory Analysis of a Randomized Placebo-controlled Study.

Pregabalin has shown opioid sparing and analgesic effects in the early postoperative period; however, perioperative effects on cognition have not been studied. A randomized, parallel group, placebo-controlled investigation in 80 donor nephrectomy patients was previously performed that evaluated the analgesic, opioid-sparing, and antihyperalgesic effects of pregabalin. This article describes a secondary exploratory analysis that tested the hypothesis that pregabalin would impair cognitive function compared to placebo. Eighty patients scheduled for donor nephrectomy participated in this randomized, placebo-controlled study. Pregabalin (150 mg twice daily, n = 40) or placebo (n = 40) was administered on the day of surgery and the first postoperative day, in addition to a pain regimen consisting of opioids, steroids, local anesthetics, and acetaminophen. Specific cognitive tests measuring inhibition, sustained attention, psychomotor speed, visual memory, and strategy were performed at baseline, 24 h, and 3 to 5 days after surgery, using tests from the Cambridge Neuropsychological Test Automated Battery. In the spatial working memory within errors test, the number of errors increased with pregabalin compared to placebo 24 h after surgery; median (25th, 75th percentile) values were 1 (0, 6) versus 0 (0, 1; rate ratio [95% CI], 3.20 [1.55 to 6.62]; P = 0.002). Furthermore, pregabalin significantly increased the number of errors in the stop-signal task stop-go test compared with placebo; median (25th, 75th percentile) values were 3 (1, 6) versus 1 (0, 2; rate ratio, 2.14 [1.13 to 4.07]; P = 0.020). There were no significant differences between groups in the paired associated learning, reaction time, rapid visual processing, or spatial working memory strategy tests. Perioperative pregabalin significantly negatively affected subdomains of executive functioning, including inhibition, and working memory compared to placebo, whereas psychomotor speed was not changed.

The role of spatial store and executive strategy in spatial working memory: a comparison between patients with obsessive–compulsive disorder and controls

ABSTRACTIntroduction: Patients with obsessive–compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM.Methods: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: α = 0.05.Results: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance.Conclusions: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.

The effects of ADHD on cognitive performance

Background: Attention-deficit hyperactivity disorder (ADHD) is a common and impairing neurodevelopmental disorder. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized test battery with standardized procedures and solid psychometric properties targeting multiple neuropsychological functions.Aims: The aim of this study was to look at the effects of ADHD on cognitive performance using CANTAB expressed as a statistical interaction term in regression modeling.Methods: We assessed 112 drug-naïve subjects (age: 7–18 years) with ADHD based on DSM IV criteria and compared them to 95 control subjects (age: 7–18 years). All participants were administered five CANTAB tasks designed to capture different aspects of executive functioning: Stockings of Cambridge (SOC), Intra/Extra dimensional shift (IED), Spatial Working Memory (SWM), Simple Reaction Time (SRT) and Stop Signal Task (SST).Results: T-tests showed a difference between ADHD and control subjects in all cognitive measures except SOC. The majority of measures showed a non-linear effect of age. SWM strategy and SST direction errors showed a linear effect of age. ADHD diagnosis had a statistically significant effect on performance. For all tests except SOC, ADHD produced the main effect without interaction with age.Discussion: For all CANTAB measures, ADHD diagnosis had a significant effect on performance and produced this effect without interaction with age in all tests except SOC, indicating that the developmental trajectories were parallel in both groups. The results indicate that cognitive performance is impaired in youth with ADHD and that CANTAB can be a valuable tool in the diagnostic assessment of ADHD.

Cognitive Function in a Randomized Trial of Evolocumab

BackgroundFindings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits.MethodsIn a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group.ResultsA total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was −0.21±2.62 in the evolocumab group and −0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, −0.52 in the evolocumab group and −0.93 in the placebo group), episodic memory (change in raw score, −1.53 and −1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes.ConclusionsIn a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. (Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634.)

Prediction of vocational participation and global role functioning in help-seeking young adults, from neurocognitive, demographic and clinical variables

BackgroundThe purpose of this study was to investigate neurocognitive, demographic and clinical correlates of vocational participation among a sample of young help-seeking adults. MethodsYoung people (18–25 years) accessing an early intervention youth health service participated. The Global Functioning: Role scale and level of vocational participation, participant characteristics (age, gender, socioeconomic background and family history of serious mental illness), distress, psychotic-like experiences, substance use, and mental health diagnoses were recorded. The Cambridge Neuropsychological Testing Automated Battery was used to assess sustained attention, visual memory and executive function. ResultsOf the 107 participants, 33 (31%) were not working or studying and 52 (49%) had a diagnosis of affective disorder. Impairments in neurocognitive tests were evidenced in attention shift, sustained attention target sensitivity, impulsivity and spatial working memory errors. Univariate analyses indicated that information processing and target impulsivity were associated with both vocational participation and global functioning, and that spatial working memory strategy was also associated with vocational participation. After controlling for significant demographic and clinical predictors, strategy formation remained a significant correlate of vocational participation (coefficient (95%CI) = −0.08 (−0.17, −0.01)), but no neurocognitive measures remained significant in the multivariate prediction of global functioning. LimitationsNeurocognitive outcomes were assessed at a single time point, factors such as fluctuations in motivation could impact on test results. ConclusionsInterventions targeting work and education participation should consider the capacity of vulnerable young people to develop appropriate plans for role success and provide support accordingly. The study also emphasised the importance of high school completion and avoidance of cannabis use, especially in males.

The Effects of Physical Activity and Fitness in Adolescence on Cognition in Adulthood and the Role of Insulin-Like Growth Factor I.

Physical activity and fitness in adolescence may improve cognition in adulthood by increasing insulin-like growth factor I (IGF-I). As part of the Amsterdam Growth and Health Longitudinal Study, following subjects from age 13 to 42 years, physical activity and fitness of 303 subjects were assessed annually between the ages 13 to 16. At mean age 36, physical activity, fitness and IGF-I were measured. At mean age 42, IGF-I and cognitive factors (ie, executive functioning and visual-spatial memory) were measured. The linear regression of physical activity and fitness in adolescence and IGF-I in adulthood on cognitive scores in adulthood was investigated. A significant association was found in males between physical activity in adolescence and executive function in adulthood (Spatial Working Memory Between Errors: β = -.18, B = -.13, 95% CI = -.259 to -.010; Spatial Working Memory Strategy: β = -.20, B = -.08, 95% CI = -.147 to -.014). No association between physical activity or fitness in adolescence and cognitive function in adulthood was found in females, nor any intermediate role for IGF-I in either sex. The results suggest a stimulating effect of adolescent physical activity in males on executive functions in adulthood, emphasizing the importance of an active lifestyle among adolescent males.

DIFFERENTIAL ASSOCIATION OF SCHIZOTYPAL TRAITS WITH STRATEGY FORMATION, GENERAL PSYCHOPATHOLOGY AND QUALITY OF LIFE IN THE SCHIZOPHRENIA SPECTRUM: FINDINGS FROM THE PREMES STUDY

ObjectiveSchizotypy may be a forerunner of schizophrenia-spectrum disorders (SSD). In this study we examined for the first time the association between schizotypy and prefrontal function, quality of life (QoL) and...

Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway.

We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.

Improvements in iron status and cognitive function in young women consuming beef or non-beef lunches.

Iron status is associated with cognitive performance and intervention trials show that iron supplementation improves mental function in iron-deficient adults. However, no studies have tested the efficacy of naturally iron-rich food in this context. This investigation measured the hematologic and cognitive responses to moderate beef consumption in young women. Participants (n = 43; age 21.1 ± 0.4 years) were randomly assigned to a beef or non-beef protein lunch group [3-oz (85 g), 3 times weekly] for 16 weeks. Blood was sampled at baseline, and weeks 8 and 16, and cognitive performance was measured at baseline and week 16. Body iron increased in both lunch groups (p < 0.0001), with greater improvement demonstrated in women with lower baseline body iron (p < 0.0001). Body iron had significant beneficial effects on spatial working memory and planning speed (p < 0.05), and ferritin responders (n = 17) vs. non-responders (n = 26) showed significantly greater improvements in planning speed, spatial working memory strategy, and attention (p < 0.05). Lunch group had neither significant interactions with iron status nor consistent main effects on test performance. These findings support a relationship between iron status and cognition, but do not show a particular benefit of beef over non-beef protein consumption on either measure in young women.

Executive functioning deficits and childhood trauma in juvenile violent offenders in China

A large body of evidence indicates that violent offenders have executive functioning deficits. However, previous studies have not considered childhood trauma, which is likely to influence the executive functioning of violent offenders. The aim of the present study was to compare the difference of executive functioning among juvenile violent offenders, with non-violent offenders and normal controls, and then to analyse whether executive functioning was affected independently of childhood trauma. In addition to using a battery of tests assessing executive functioning including the Intra/Extradimensional Shift Test(IED), the Stockings of Cambridge Test (SOC), and the Spatial Working Memory Test (SWM) from the Cambridge Automated Neuropsychological Testing Battery (CANTAB), the short form of the Chinese Revision of the Wechsler Adult Intelligence Scale (WAIS-RC) and Childhood Trauma Questionnaire-28 item Short Form (CTQ) were also used among 107 violent offenders, 107 non-violent offenders and 107 normal controls. Our results showed that both offender groups obtained significantly lower estimated Intelligence Quotient (IQ) scores and experienced more childhood trauma than did normal controls. Violent offenders showed impaired executive functioning on tasks of attention set-shifting, working memory and planning. Finally, spatial working memory (SWM) deficits, particularly SWM strategy scores, may be associated with childhood trauma.

A Randomized, Double-Blind, Placebo-Controlled Trial of Fluvoxamine in Patients With Schizophrenia

Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-Åsberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-Åsberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.

Vitamin D status and measures of cognitive function in healthy older European adults

Data from human studies that have investigated the association between vitamin D status and cognitive function in elderly adults are conflicting. The objective of this study was to assess vitamin D status (reflected by serum 25-hydroxyvitamin D (25(OH)D)) in older European subjects (n=387; aged 55-87 years) and examine its association with measures of cognitive function. Serum 25(OH)D was assessed using enzyme-linked immunosorbent assay, whereas measures of cognitive function were assessed using a comprehensive Cambridge Neuropsychological Testing Automated Battery (CANTAB). In all, 12, 36 and 64% of subjects had serum 25(OH)D concentrations <30, <50 and <80 nmol/l, respectively, throughout the year. Serum 25(OH)D was significantly and inversely correlated with four assessments within the spatial working memory (SWM) test parameter (SWM between errors (r=-0.166; P=0.003); SWM between errors 8 boxes (r=-0.134; P=0.038); SWM strategy (r=-0.246; P<0.0001); and SWM total errors (r=-0.174; P<0.003)). When subjects were stratified on the basis of tertiles (T) of serum 25(OH)D (<47.6 (T(1)); 47.6-85.8 (T(2)); and >85.8 (T(3)) nmol/l), fewer errors in SWM test scores occurred in subjects in the third T when compared with the first T (P<0.05-0.084). Stratification by sex showed that these differences between tertiles strengthened (P<0.001-0.043) in the females, but the differences were not significant (P>0.6) in males. Vitamin D insufficiency, but not deficiency, is widespread in the older population of several European countries. Low vitamin D status was associated with a reduced capacity for SWM, particularly in women.

Gender influences the detection of spatial working memory deficits in bipolar disorder

Despite evidence that gender may influence neurocognitive functioning, few studies have examined its effects in bipolar disorder (BD) a priori. The aim of this study was to examine how gender influences executive-type functions, which are potentially useful as endophenotypes for BD. The performance of 26 euthymic patients (12 males, 14 females) with DSM-IV BD (20 BD type I and six BD type II) was compared to that of 26 controls (12 males, 14 females) on tests of executive function. Controls were matched to patients on an individual basis for sex, age and premorbid IQ. Tests assessed spatial working memory (SWM), planning, attentional set-shifting and verbal fluency. Overall, patients showed deficits in SWM strategy (p < 0.001) and made more SWM errors relative to controls (p < 0.001). These deficits were more apparent in male-only comparisons (both p < 0.001) than in female-only comparisons (both p < 0.05). When examined in isolation, male controls were significantly better at performing the SWM task than female controls (both p < 0.05). This pattern was not observed in the patient cohort: male patients had poorer strategy scores than female patients (p < 0.05), but made a similar number of SWM errors. These findings provide evidence that gender can influence the detection of SWM deficits in the euthymic phase of BD, as the sex-related disequilibrium in SWM identified in healthy controls was disrupted in BD.

Acetylcholine release in hippocampus and striatum during testing on a rewarded spontaneous alternation task

The present experiment tested male Sprague–Dawley rats for spontaneous alternation performance in a food-rewarded Y-shaped maze. Microdialysis samples, later assessed for acetylcholine concentration, were collected from the hippocampus and striatum of each rat prior to and during testing; testing sessions lasted 20 min. Early in testing, rats alternated at a rate of 72%. Alternation scores increased throughout the 20-min testing session and reached 93% during the last 5 min. The behavioral findings suggest that, during testing, rats changed the basis for their performance from a spatial working memory strategy to a persistent turning strategy. ACh release in both hippocampus and striatum increased at the onset of testing. Increases in ACh release in the striatum began at 18% above baseline during the first 5 min of testing and steadily increased reaching 58% above baseline during the final 5 min. The progressive rise of striatum ACh release during testing occurred at about the time rats adopted a persistent turning strategy. In contrast, ACh release in the hippocampus increased by 50% with the onset of testing and remained at this level until declining slightly during the last 5 min of testing. The relative changes in ACh release in the striatum and hippocampus resulted in a close negative relationship between the ratio of ACh release in the hippocampus/striatum and alternation scores.