Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error

Isolation of Mycobacterium avium Subspecies paratuberculosis Reactive CD4 T Cells from Intestinal Biopsies of Crohn's Disease Patients

BACKGROUND:Crohn's disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is unknown, but an excessive immune response to bacteria in genetically susceptible individuals is probably involved. The response is characterized by a strong Th1/Th17 response, but the relative importance of the various bacteria is not known. METHODOLOGY/PRINCIPAL FINDINGS:In an attempt to address this issue, we made T-cell lines from intestinal biopsies of patients with CD (n = 11), ulcerative colitis (UC) (n = 13) and controls (n = 10). The T-cell lines were tested for responses to various bacteria. A majority of the CD patients with active disease had a dominant response to Mycobacterium avium subspecies paratuberculosis (MAP). The T cells from CD patients also showed higher proliferation in response to MAP compared to UC patients (p<0.025). MAP reactive CD4 T-cell clones (n = 28) were isolated from four CD patients. The T-cell clones produced IL-17 and/or IFN-gamma, while minimal amounts of IL-4 were detected. To further characterize the specificity, the responses to antigen preparations from different mycobacterial species were tested. One T-cell clone responded only to MAP and the very closely related M. avium subspecies avium (MAA) while another responded to MAP, MAA and Mycobacterium intracellulare. A more broadly reactive T-cell clone reacted to MAP1508 which belongs to the esx protein family. CONCLUSIONS/SIGNIFICANCE:The presence of MAP reactive T cells with a Th1 or Th1/Th17 phenotype may suggest a possible role of mycobacteria in the inflammation seen in CD. The isolation of intestinal T cells followed by characterization of their specificity is a valuable tool to study the relative importance of different bacteria in CD

Validation of the Virtual Reality Everyday Assessment Lab (VR-EAL):An immersive virtual reality neuropsychological battery with enhanced ecological validity

International audienceObjective: The assessment of cognitive functions such as prospective memory, episodic memory, attention, and executive functions benefits from an ecologically valid approach to better understand how performance outcomes generalize to everyday life. Immersive virtual reality (VR) is considered capable of simulating real-life situations to enhance ecological validity. The present study attempted to validate the Virtual Reality Everyday Assessment Lab (VR-EAL), an immersive VR neuropsychological battery, against an extensive paper-andpencil neuropsychological battery. Methods: Forty-one participants (21 females) were recruited: 18 gamers and 23 non-gamers who attended both an immersive VR and a paper-and-pencil testing session. Bayesian Pearson correlation analyses were conducted to assess construct and convergent validity of the VR-EAL. Bayesian t-tests were performed to compare VR and paper-and-pencil testing in terms of administration time, similarity to real life tasks (i.e., ecological validity), and pleasantness. Results: VR-EAL scores were significantly correlated with their equivalent scores on the paper-and-pencil tests. The participants' reports indicated that the VR-EAL tasks were significantly more ecologically valid and pleasant than the paper-and-pencil neuropsychological battery. The VR-EAL battery also had a shorter administration time. Conclusion: The VR-EAL appears as an effective neuropsychological tool for the assessment of everyday cognitive functions, which has enhanced ecological validity, a highly pleasant testing experience, and does not induce cybersickness

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder:results from the BeSt InTro study

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results

Cognitive reserve proxies do not differentially account for cognitive performance in patients with focal frontal and non-frontal lesions

Objective: Cognitive reserve (CR) suggests that premorbid efficacy, aptitude, and flexibility of cognitive processing can aid the brain\u2019s ability to cope with change or damage. Our previous work has shown that age and literacy attainment predict the cognitive performance of frontal patients on frontal-executive tests. However, it remains unknown whether CR also predicts the cognitive performance of non-frontal patients. Method: We investigated the independent effect of a CR proxy, National Adult Reading Test (NART) IQ, as well as age and lesion group (frontal vs. non-frontal) on measures of executive function, intelligence, processing speed, and naming in 166 patients with focal, unilateral frontal lesions; 91 patients with focal, unilateral non-frontal lesions; and 136 healthy controls. Results: Fitting multiple linear regression models for each cognitive measure revealed that NART IQ predicted executive, intelligence, and naming performance. Age also significantly predicted performance on the executive and processing speed tests. Finally, belonging to the frontal group predicted executive and naming performance, while membership of the non-frontal group predicted intelligence. Conclusions: These findings suggest that age, lesion group, and literacy attainment play independent roles in predicting cognitive performance following stroke or brain tumour. However, the relationship between CR and focal brain damage does not differ in the context of frontal and non-frontal lesions

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Identification of temporal consistency in rating curve data : Bidirectional Reach (BReach)

In this paper, a methodology is developed to identify consistency of rating curve data based on a quality analysis of model results. This methodology, called Bidirectional Reach (BReach), evaluates results of a rating curve model with randomly sampled parameter sets in each observation. The combination of a parameter set and an observation is classified as nonacceptable if the deviation between the accompanying model result and the measurement exceeds observational uncertainty. Based on this classification, conditions for satisfactory behavior of a model in a sequence of observations are defined. Subsequently, a parameter set is evaluated in a data point by assessing the span for which it behaves satisfactory in the direction of the previous (or following) chronologically sorted observations. This is repeated for all sampled parameter sets and results are aggregated by indicating the endpoint of the largest span, called the maximum left (right) reach. This temporal reach should not be confused with a spatial reach (indicating a part of a river). The same procedure is followed for each data point and for different definitions of satisfactory behavior. Results of this analysis enable the detection of changes in data consistency. The methodology is validated with observed data and various synthetic stage-discharge data sets and proves to be a robust technique to investigate temporal consistency of rating curve data. It provides satisfying results despite of low data availability, errors in the estimated observational uncertainty, and a rating curve model that is known to cover only a limited part of the observations