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A relationship between excessive sugar consumption and cognitive function has been described in animal models, but the specific effects of sugars in humans remains unclear. This systematic review and meta-analysis aimed to evaluate the current knowledge, research characteristics, and quality of evidence of studies investigating the impacts of free and added sugars on human cognition in healthy participants. The review identified 77 studies (65 experimental trials, n = 3831; 9 cross-sectional studies, n = 11,456; and 3 cohort studies, n = 2059). All cohort studies and eight of the nine cross-sectional studies found significant positive correlations between added sugar consumption and risk of cognitive impairment. Four studies identified reduced risk of cognitive impairment associated with natural fructose-containing foods. The majority of randomised control trials assessed short-term glucose facilitation effects on cognitive outcomes. The results from these studies suggest the need for a tightly regulated blood glucose level, dependent on individualised physiological factors, for optimal cognitive function. A meta-analysis of a subset of studies that assessed the impact of glucose on recall found improvements in immediate free recall compared to controls ( p = 0.002). The findings highlight the potentially detrimental effect of excessive, long-term, or prenatal added sugar consumption on cognitive function. Further research is needed to examine the specific effects of free and added sugars on cognitive function.

BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.

Background: There is evidence of brain recovery on brain magnetic resonance imaging (MRI) early postliver transplant (LT), but the longer-term impact is unclear. The aim of this study was to determine the change in brain MRI parameters, cognition, and health-related quality of life (HRQOL) between 6 and 12 months post-LT., Methods: Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre-LT, 6 months (post-LT1), and 1-year (post-LT2) post-LT. Assessment of MRI changes between visits was performed for ammonia-associated metabolite changes using magnetic resonance spectroscopy, white matter changes using tract-based spatial statistics analysis on diffusion tensor imaging data and grey matter changes using voxel-based morphometry analysis on 3D high resolution T1-weighted images., Results: Forty-five patients were included, of which 23 were tested at all visits. Cognitive and HRQOL scores improved between all visits compared with pre-LT values. This trend continued on magnetic resonance spectroscopy with reduced glutamine + glutamate and higher myoinositol, choline between pre-LT/post-LT1 but lower degrees of improvement between post-LT1/post-LT2. On diffusion tensor imaging, mean diffusivity, linear diffusivity and mode of anisotropy continued to increase in the posterior internal capsule at both post-LT visits. On voxel-based morphometry, a continued increase was seen in basal ganglia grey matter between both post-LT visits was seen., Conclusions: HRQOL and cognition continue to improve compared with pre-LT values up to 1 year post-LT, although the rate of improvement slows down after 6 months. Grey matter increase is steady over time at 1 year although changes in ammonia-related metabolites and white matter integrity improve at a slower pace at 1 year post-LT.

Liver transplantation (LT) improves daily function and cognition in patients with cirrhosis, but a subset of patients can remain impaired. Unfavorable microbiota or dysbiosis is observed in patients with cirrhosis, but the effect of LT on microbial composition, especially with poor post-LT cognition, is unclear. The aims were to determine the effect of LT on gut microbiota and to determine whether gut microbiota are associated with cognitive dysfunction after LT. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Cognition (Psychometric Hepatic Encephalopathy score [PHES]), health-related quality of life (HRQOL), and stool microbiota (multitagged sequencing for diversity and taxa) tests were performed at both visits. Persistent cognitive impairment was defined as a stable/worsening PHES. Both pre-/post-LT data were compared with age-matched healthy controls. We enrolled 45 patients (56 ± 7 years, Model for End-Stage Liver Disease score 26 ± 8). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 2 months after LT with a stable course. A significantly improved HRQOL, PHES, with increase in microbial diversity, increase in autochthonous, and decrease in potentially pathogenic taxa were seen after LT compared with baseline. However, there was continued dysbiosis and HRQOL/cognitive impairment after LT compared with controls in 29% who did not improve PHES after LT. In these, Proteobacteria relative abundance was significantly higher and Firmicutes were lower after LT, whereas the reverse occurred in the group that improved. Delta PHES was negatively correlated with delta Proteobacteria and positively with delta Firmicutes. In conclusion, LT improves gut microbiota diversity and dysbiosis compared with pre-LT baseline but residual dysbiosis remains compared with controls. There is cognitive and HRQOL enhancement in general after LT, but a higher Proteobacteria relative abundance change is associated with posttransplant cognitive impairment. Liver Transplantation 23 907-914 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Background & Aims: In patients with cirrhosis, sleep disturbances are assumed to result from hepatic encephalopathy (HE). The effects of obstructive sleep apnea (OSA) on cognition, sleep parameters, or driving in patients with cirrhosis are unclear., Methods: We performed a cross-sectional and prospective study of 118 subjects. Subjects were assigned to 1 of 4 groups: those with OSA and cirrhosis (without hepatic encephalopathy or ascites, n = 34), those with cirrhosis only (n = 30), those with OSA only (n = 29), and those without OSA or cirrhosis (controls, n = 25). None of the OSA patients were receiving continuous positive airway pressure (CPAP) therapy. Subjects underwent cognitive testing (paper-pencil tests for psychomotor speed and attention, as well as executive function tests), sleep assessment (daytime sleepiness and night-time sleep quality), and a monotonous driving simulation (worsening lane deviations over time indicated poor performance). We also tested patients with OSA, with cirrhosis (n = 10) and without cirrhosis (n = 7), before and after CPAP therapy., Results: Daytime sleepiness and sleep quality were worse in subjects in the OSA groups (with or without cirrhosis) than subjects with cirrhosis alone or controls. Of subjects with only OSA, 36% had impaired psychomotor speed and attention, compared with more than 60% of subjects in both cirrhosis groups. In contrast, executive function was uniformly worse in subjects with OSA, with or without cirrhosis, than groups without OSA. Simulator performance (lane deviations) worsened over time in both OSA groups. CPAP therapy significantly increased executive function and sleep quality, and reduced simulator lane deviations and sleepiness, in OSA subjects with and without cirrhosis. After CPAP therapy, performance on the paper-pencil test improved significantly only in subjects with OSA without cirrhosis., Conclusions: OSA should be considered in evaluating sleep impairment in patients with cirrhosis. In patients with cirrhosis and OSA, psychomotor speed and attention issues likely are related to cirrhosis, whereas executive function and simulator performance are affected by OSA. CPAP therapy improves executive function and simulator performance in patients with OSA, regardless of cirrhosis., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Hyponatraemia in cirrhosis is associated with impaired cognition and poor health-related quality of life (HRQOL). However, the benefit of hyponatraemia correction is unclear. The aim of this study was to evaluate the effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics with hyponatraemia., Methods: Cirrhotics with Na <130 mEq/L were included for a four-week trial. At screening, patients underwent cognitive and HRQOL testing, serum/urine chemistries and companion burden assessment. Patients then underwent fluid restriction and diuretic withdrawal for two weeks after which cognitive tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging (MRI) was performed and tolvaptan was initiated for 14 days with frequent clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were repeated. Comparisons were made between screen, pre-and post-drug periods Na, urine/serum laboratories, cognition, HRQOL and companion burden., Results: 24 cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement in cognition. The remaining 17 received tolvaptan of which 14 completed the study over 13 ± 2 days (age 58 ± 6 years, MELD 17, 55% HCV, median 26 mg/day of tolvaptan). Serum Na and urine free water clearance increased with tolvaptan without changes in mental status or liver function. Cognitive function, HRQOL and companion burden only improved in these 14 patients after tolvaptan, along with reduced total brain and white matter volume, increase in choline on magnetic resonance spectroscopy, and reduced cytotoxic oedema., Conclusions: Short-term tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is associated with cognitive, HRQOL, brain MRI and companion burden improvement., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Using Gray and McNaughton's (2000) revised reinforcement sensitivity theory (r-RST), we examined the influence of personality on processing of words presented in gain-framed and loss-framed anti-speeding messages and how the processing biases associated with personality influenced message acceptance. The r-RST predicts that the nervous system regulates personality and that behaviour is dependent upon the activation of the behavioural activation system (BAS), activated by reward cues and the fight-flight-freeze system (FFFS), activated by punishment cues. According to r-RST, individuals differ in the sensitivities of their BAS and FFFS (i.e., weak to strong), which in turn leads to stable patterns of behaviour in the presence of rewards and punishments, respectively. It was hypothesised that individual differences in personality (i.e., strength of the BAS and the FFFS) would influence the degree of both message processing (as measured by reaction time to previously viewed message words) and message acceptance (measured three ways by perceived message effectiveness, behavioural intentions, and attitudes). Specifically, it was anticipated that, individuals with a stronger BAS would process the words presented in the gain-frame messages faster than those with a weaker BAS and individuals with a stronger FFFS would process the words presented in the loss-frame messages faster than those with a weaker FFFS. Further, it was expected that greater processing (faster reaction times) would be associated with greater acceptance for that message. Driver licence holding students (N=108) were recruited to view one of four anti-speeding messages (i.e., social gain-frame, social loss-frame, physical gain-frame, and physical loss-frame). A computerised lexical decision task assessed participants' subsequent reaction times to message words, as an indicator of the extent of processing of the previously viewed message. Self-report measures assessed personality and the three message acceptance measures. As predicted, the degree of initial processing of the content of the social gain-framed message mediated the relationship between the reward sensitive trait and message effectiveness. Initial processing of the physical loss-framed message partially mediated the relationship between the punishment sensitive trait and both message effectiveness and behavioural intention ratings. These results show that reward sensitivity and punishment sensitivity traits influence cognitive processing of gain-framed and loss-framed message content, respectively, and subsequently, message effectiveness and behavioural intention ratings. Specifically, a range of road safety messages (i.e., gain-frame and loss-frame messages) could be designed which align with the processing biases associated with personality and which would target those individuals who are sensitive to rewards and those who are sensitive to punishments., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A relationship between excessive sugar consumption and cognitive function has been described in animal models, but the specific effects of sugars in humans remains unclear. This systematic review and meta-analysis aimed to evaluate the current knowledge, research characteristics, and quality of evidence of studies investigating the impacts of free and added sugars on human cognition in healthy participants. The review identified 77 studies (65 experimental trials, n = 3831; 9 cross-sectional studies, n = 11,456; and 3 cohort studies, n = 2059). All cohort studies and eight of the nine cross-sectional studies found significant positive correlations between added sugar consumption and risk of cognitive impairment. Four studies identified reduced risk of cognitive impairment associated with natural fructose-containing foods. The majority of randomised control trials assessed short-term glucose facilitation effects on cognitive outcomes. The results from these studies suggest the need for a tightly regulated blood glucose level, dependent on individualised physiological factors, for optimal cognitive function. A meta-analysis of a subset of studies that assessed the impact of glucose on recall found improvements in immediate free recall compared to controls (p = 0.002). The findings highlight the potentially detrimental effect of excessive, long-term, or prenatal added sugar consumption on cognitive function. Further research is needed to examine the specific effects of free and added sugars on cognitive function. [ABSTRACT FROM AUTHOR]

The importance of nutrition in human health has been understood for over a century. However, debate is ongoing regarding the role of added and free sugars in physiological and neurological health. In this narrative review, we have addressed several key issues around this debate and the major health conditions previously associated with sugar. We aim to determine the current evidence regarding the role of free sugars in human health, specifically obesity, diabetes, cardiovascular diseases, cognition, and mood. We also present some predominant theories on mechanisms of action. The findings suggest a negative effect of excessive added sugar consumption on human health and wellbeing. Specific class and source of carbohydrate appears to greatly influence the impact of these macronutrients on health. Further research into individual effects of carbohydrate forms in diverse populations is needed to understand the complex relationship between sugar and health. [ABSTRACT FROM AUTHOR]

Background: To date, research has found variable success in using attentional bias modification training (ABMT) procedures in pain samples. Several factors could contribute to these mixed findings, including boredom and low motivation. Indeed, training paradigms are repetitive, which can lead to disengagement and high dropout rates. A potential approach to overcoming some of these barriers is to attempt to increase motivation and engagement through gamification (ie, the use of game elements) of this procedure. To date, research has yet to explore the gamified format of ABMT for chronic pain and its potential for the transfer of benefits. Objective: The aim of this study is to investigate the effects of a gamified web-delivered ABMT intervention in a sample of adults with chronic pain via a randomized, double-blind, placebo-controlled trial. Methods: A total of 120 adults with chronic musculoskeletal pain, recruited from clinical (hospital outpatient waiting list) and nonclinical (wider community) settings, will be included in this randomized, double-blind, placebo-controlled, 3-arm trial. Participants will be randomly assigned to complete 6 web-based sessions of dot-probe nongamified sham control ABMT, nongamified standard ABMT, or gamified ABMT across a period of 3 weeks. Active ABMT conditions will aim to train attention away from pain-relevant words. Participant outcomes will be assessed at pretraining, during training, immediately after training, and at the 1-month follow-up. Primary outcomes include pain intensity, pain interference, and behavioral and self-reported engagement. Secondary outcomes include attentional bias for pain, anxiety, depression, interpretation bias for pain, and perceived improvement. Results: The ethical aspects of this research project have been approved by the human research ethics committees of the Royal Brisbane and Women’s Hospital (HREC/2020/QRBW/61743) and Queensland University of Technology (2000000395). Study recruitment commenced in August 2021 and is ongoing. Data collection and analysis are expected to be concluded by October 2022 and January 2023, respectively. Conclusions: This trial will be the first to evaluate the effects of gamification techniques in a pain ABMT intervention. The findings will provide important information on the potential therapeutic benefits of gamified pain ABMT programs, shed light on the motivational influences of certain game elements in the context of pain, and advance our understanding of chronic pain. [ABSTRACT FROM AUTHOR]

Background: Hepatic encephalopathy (HE) is considered reversible regarding mental status but may not be cognitively in single-center studies.Aim: To evaluate persistence of learning impairment in prior HE compared to those who never experienced HE (no-HE) in a multicenter study.Methods: A total of 174 outpatient cirrhotics from three centers (94 Virginia, 30 Ohio, and 50 Rome; 36 prior HE) underwent psychometric hepatic encephalopathy score (PHES) and inhibitory control (ICT) testing at baseline and then at least 7 days apart. ICT learning (change in 2nd half lures compared to 1st half) was compared between patient groups at both visits. Change in the PHES individual sub-tests and total score between visits was compared in both groups. US versus Italian trends were also analyzed.Results: HE patients had worse PHES and ICT results compared to no-HE patients at baseline. Significant improvement (1st half 7.1 vs. 2nd half 6.2, p < 0.0001) was observed in no-HE, but not in HE (1st half 7.9 vs. 2nd half 7.8, p = 0.1) at baseline. At retesting (median 20 days later), no-HE patients continued with significant learning (1st half 6.0 vs. 2nd half 5.4, p < 0.0001), while HE patients again did not improve (1st half 7.8 vs. 2nd half 6.9, p = 0.37). Between visits, no-HE patients improved significantly on four PHES sub-tests and overall score, while HE patients only improved on two sub-tests with similar overall PHES score. Trends were similar between US and Italian subjects.Conclusion: In this multicenter study, prior HE patients showed persistent significant learning impairment compared to those without prior HE, despite adequate medical therapy. This persistent change should increase efforts to reduce the first HE episode. [ABSTRACT FROM AUTHOR]

Cirrhosis is associated with a systemic proinflammatory milieu, endotoxemia, and gut dysbiosis. The oral cavity could be an additional source of inflammation. We aimed to determine the effect of periodontal therapy in cirrhosis through evaluating endotoxemia, inflammation, cognition, and quality of life (QOL). Age-matched cirrhotic and noncirrhotic subjects exhibiting chronic gingivitis and/or mild or moderate periodontitis underwent periodontal therapy with follow-up at 30 days. Saliva/stool for microbial composition and serum for Model for End-stage Liver Disease (MELD) score, endotoxin and lipopolysaccharide binding protein (LBP) and immune-inflammatory markers (IL-1β; IL-6; histatins 1, 3, 5; and lysozyme) were collected at baseline and day 30. The cognitive function and QOL were also evaluated similarly. A separate group of cirrhotic patients were followed for the same duration without periodontal therapy. Cirrhotics, especially those with hepatic encephalopathy (HE), demonstrated improved dysbiosis in stool and saliva, and improved endotoxin, LBP, and salivary and serum inflammatory mediators following periodontal therapy. These parameters, which were higher in HE at baseline, became statistically similar posttherapy. Pretherapy vs. posttherapy QOL and cognition also improved in HE patients following oral interventions. On the other hand, LBP and endotoxin increased over time in cirrhotic patients not receiving therapy, but the rest of the parameters, including microbiota remained similar over time in the no-therapy group. This proof-of-concept study demonstrates that periodontal therapy in cirrhosis, especially in those with HE, is associated with improved oral and gut dysbiosis, systemic inflammation, MELD score, and cognitive function, which was not observed in those who did not receive therapy over the same time period. [ABSTRACT FROM AUTHOR]

Objectives: Disordered eating behavior in young adults with type 1 diabetes is overrepresented and associated with significant negative health consequences. Thus, determining the key correlates of these behaviors is essential. The aim of the present study was to determine the association between executive function and disordered eating in young adults with type 1 diabetes, relative to a control group without diabetes.Methods: 74 young adults with type 1 diabetes and 201 demographically similar control participants completed an online survey containing the Eating Disorders Examination Questionnaire (EDE-Q), Diabetes Eating Problems Survey- Revised (DEPS-R), Behavior Rating Inventory of Executive Function- Adult version, Depression Anxiety and Stress Scales, and 3 subscales of the Family Environment Scale (independence, control, and cohesion).Results: Hierarchical multiple regressions showed that lower executive function was associated with significantly greater disordered eating (as measured by the DEPS-R) over and above psychological and family functioning in the type 1 diabetes group (ΔR2 = 0.056, β = 0.366, p = .031). The same relationship was not found when disordered eating was measured by the EDE-Q in either the diabetes group (ΔR2 = 0.049, β = 0.342, p = .054), or the control group (ΔR2 = 0.010, β = 0.136, p = .100).Conclusions: Executive function may play a greater role in the development and/or maintenance of disordered eating in groups with type 1 diabetes relative to those without. This relationship may contribute to the over-representation of eating problems in this clinical group, and may represent a target for prevention or intervention. [ABSTRACT FROM AUTHOR]

We review 20 studies that examined persuasive processing and outcomes of health messages using neurocognitive measures. The results suggest that cognitive processes and neural activity in regions thought to reflect self-related processing may be more prominent in the persuasive process of self-relevant messages. Furthermore, activity in the medial prefrontal cortex, the superior temporal gyrus and the middle frontal gyrus were identified as predictors of message effectiveness, with the medial prefrontal cortex accounting for additional variance in behaviour change beyond that accounted for by self-report measures. Incorporating neurocognitive measures may provide a more comprehensive understanding of the processing and outcomes of health messages. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis: Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods: Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results: 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92 % medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia( p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Methods: Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. Results: There was a significant improvement in cognition(six of seven tests improved,p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar. Conclusions: Rifaximin is associated with improved cognitive function and endotoxemia in MHE, which is accompanied by alteration of gut bacterial linkages with metabolites without significant change in microbial abundance. Trial Registration: ClinicalTrials.gov NCT01069133 [ABSTRACT FROM AUTHOR]

Background & Aims: In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). Methods: Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol, block design, and number connection [NCT-A and B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and first minus second halves (ΔL1–2) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotic patients with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. Results: In study A (226 cirrhotic patients), 54 had experienced OHE, 120 had minimal HE, and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotic patients were cognitively impaired, based on results from all tests. Learning of response inhibition (ΔL1–2 ≥1) was evident in patients with minimal HE and no minimal HE but was lost after OHE. In study B (50 additional patients who developed ≥1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r = 0.5, P = .0001), digit symbol test (r = −0.39, P = .002), and number connection test-B (r = 0.33, P = .04). In the prospective study (59 cirrhotic patients without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs 18 after, P = .0003), and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. Conclusions: In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning. [Copyright &y& Elsevier]

Objective: Factors which may render females with type 1 diabetes mellitus (T1DM) vulnerable to disordered eating behavior or difficulties with dietary management require further investigation. Given prior associations observed between food-related attentional biases and eating behavior in groups without diabetes, this study explored the relationships between attentional bias to healthy and unhealthy pictorial food cues and disordered eating in young adult females with and without T1DM, aged 18-40yrs.Methods: 97 participants (41 with T1DM, 56 without) completed an initial online survey assessing demographic and clinical information, and disordered eating via the Eating Disorders Examination- Questionnaire (EDE-Q). They subsequently attended an in-person session to complete a computer-based visual probe task to assess attentional bias to pictorial food cues.Results: Analyses of Variance (ANOVAs) adjusting for age and body mass index showed a unique significant relationship in the group with T1DM whereby greater attentional bias scores away from unhealthy foods was associated with greater disordered eating. No relationship was observed in the group without diabetes.Discussion: This study suggests that early attentional disengagement from food-related cues may be uniquely associated with eating-related outcomes for females with T1DM relative to those without diabetes. This should be further explored in future research with an aim to develop novel strategies for prevention and treatment of disordered eating behavior in this vulnerable group. [ABSTRACT FROM AUTHOR]

Polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster (Chr15q25) have been robustly associated with nicotine dependence, including genome-wide studies, as well as with cognitive and neuropsychological measures. In addition, cognitive processes can be influenced by nicotine use through nicotinic acetylcholine receptors (nAChRs). Here, we evaluated the effect of polymorphisms in CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction with tobacco smoking status on cognition in patients with Attention Deficit/Hyperactivity Disorder (ADHD). Eight SNPs from the CHRNA5-CHRNA3-CHRNB4 gene cluster were evaluated on a clinical sample of 403 adults with ADHD. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Analyses of covariance were used to assess the influence of single markers and their interaction with smoking status in the Vocabulary and Block Design subtests of WAIS-R. Correction for multiple comparisons was applied. Lifetime smoking was associated to Vocabulary subtest. The TT genotypes of CHRNA5 SNPs rs588765 and rs514743 showed a trend towards association with, respectively, higher and lower scores on the Vocabulary subtest. There was a significant interaction between intergenic SNP rs8023462 and smoking on Vocabulary scores. Our results are consistent with an influence of variants in the CHRNA5 – CHRNA3 – CHRNB4 gene cluster on cognitive measures. The overall scenario suggests a pleiotropic role of Chr15q25 nicotinic gene cluster with complex influences in ADHD, tobacco smoking and cognitive performance, characteristics that can be partially interdependent and may share underlying genetic factors. [ABSTRACT FROM AUTHOR]

Summary: Neurons important for cognitive function are often classified by their morphology and integrative properties. However, it is unclear if within a single class of neuron these properties tune synaptic responses to the salient features of the information that each neuron represents. We demonstrate that for stellate neurons in layer II of the medial entorhinal cortex, the waveform of postsynaptic potentials, the time window for detection of coincident inputs, and responsiveness to gamma frequency inputs follow a dorsal-ventral gradient similar to the topographical organization of grid-like spatial firing fields of neurons in this area. We provide evidence that these differences are due to a membrane conductance gradient mediated by HCN and leak potassium channels. These findings suggest key roles for synaptic integration in computations carried out within the medial entorhinal cortex and imply that tuning of neural information processing by membrane ion channels is important for normal cognitive function. [Copyright &y& Elsevier]