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Alzheimer’s Disease (AD) is the leading cause of dementia. Epidemiological studies suggest that AD is linked with poor status of nutrients including DHA, B-vitamins and the vitamins E and C. Ongoing neurodegeneration, particularly synaptic loss, leads to the classical clinical features of AD namely, memory impairment, language deterioration, and executive and visuospatial dysfunction. The main constituents of neural and synaptic membranes are phospholipids. Supplemenation of animals with three dietary precursors of phospholipids namely, DHA, uridine monophosphate and choline, results in increased levels of brain phospholipids, synaptic proteins, neurite outgrowth, dendritic spines formation (i.e. the anatomical precursors of new synapses) and an improvement in learning and memory. Other nutrients act as co-factors in the synthesis pathway of neuronal membranes. For example B-vitamins are involved in methylation processes, thereby enhancing the availability of choline as a synaptic membrane precursor. A multi-nutrient concept that includes these nutrients may improve membrane integrity, thereby influencing membrane-dependent processes such as receptor function and amyloid precursor protein (APP) processing, as shown by reduced amyloid production and amyloid β plaque burden, as well as toxicity. Together, these insights provided the basis for the development of a medical food for patients with AD, Souvenaid®, containing a specific combination of nutrients (Fortasyn™ Connect) and designed to enhance synapse formation in AD. The effect of Souvenaid on memory and cognitive performance was recently assessed in a proof-of-concept study, SOUVENIR I, with 212 drug-naïve mild AD patients (MMSE 20-26). This proof-of-concept study demonstrated that oral nutritional supplementation with Souvenaid® for 12 weeks improves memory in patients with mild AD. To confirm and extend these findings, we have designed and initiated three additional studies. Two of these studies will be completed in 2011; Souvenir II, a 24-week European study, with 259 drug-naïve mild AD patients (MMSE≥20) and S-Connect, another 24-week study, with 527 mild-tomoderate AD patients (MMSE 14-24) using AD medication conducted in the US. The third is the EU-funded LipiDiDiet study, a 24-month study, which will enrol 300 people with prodromal AD to assess the effect on memory performance.

Abstract Background Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats. Methods In a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4 weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4 weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4 weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins. Results Plasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (P = 0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (P = 0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (P > 0.05 vs. normal, P . enriched and high) and highest in rats consuming the B-vitamin-high diet (P . poor and normal, P > 0.05 vs. enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine. Conclusion These data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.

Introduction: Screening for early esophageal adenocarcinoma (EAC) may potentially reduce EAC-related mortality and morbidity. This study aimed to examine the Dutch population's intended uptake of 3 hypothetical EAC screening test scenarios and preferences for potential future organization., Methods: A total of 8,350 Dutch individuals aged 45-75 years were invited, of whom 2,258 completed a web-based survey. Participants were randomly assigned to 1 of 3 hypothetical screening test scenarios (i.e., transnasal endoscopy, ingestible cell collection device, or breath analysis). The primary outcome was intended uptake. Secondary outcomes included acceptance of screening eligibility criteria and preferences regarding invitation, counseling, and diagnostic follow-up. We performed exploratory univariable and multivariable regression analyses to assess which determinants were associated with EAC screening intent., Results: Intended uptake of screening was highest in the breath analysis scenario (95%), followed by conventional upper endoscopy (78%), an ingestible cell collection device (75%), and transnasal endoscopy (68%) ( P < 0.001). Anticipating discomfort was most strongly associated with decreased intention to undergo transnasal endoscopy (odds ratio 0.18, 95% confidence interval 0.11-0.29) or swallow a cell collection device (odds ratio 0.20, 95% confidence interval 0.13-0.32). Cancer worry and high acceptance of test sensitivity/specificity were consistently associated with a positive intention to participate in screening. Inviting persons for screening based on gastroesophageal reflux disease symptoms, age, or the output of a risk prediction model was acceptable to 74%, 69%, and 66%, respectively. Inviting only men was acceptable for only 41% of women. The majority (58%) preferred to be invited by a public health organization, and 32% of the participants preferred to discuss their decision to participate with a healthcare professional., Discussion: Participants in this study self-selected through a web-based survey, potentially introducing selection bias. Participants generally intended to participate in EAC screening, although the level of intent depended on the discomfort and performance associated with the offered screening test. Determining eligibility based on gastroesophageal reflux disease symptoms, age, or a risk calculator, but not sex, would be acceptable to most individuals., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking., Methods: We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month)., Results: The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87)., Conclusion: Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes., (© 2024. The Author(s).)

As we continue to elucidate the mechanisms underlying age-related brain diseases, the reductionist strategy in nutrition–brain function research has focused on establishing the impact of individual foods. However, the biological processes connecting diet and cognition are complex. Therefore, consideration of a combination of nutritional compounds may be most efficacious. One barrier to establishing the efficacy of multi-nutrient interventions is that the area lacks an established set of evidence-based guidelines for studying their effect on brain health. This review is an output of the International Life Sciences Institute (ILSI) Europe. A multi-disciplinary expert group was assembled with the aim of developing a set of considerations to guide research into the effects of multi-nutrient combinations on brain functions. Consensus recommendations converged on six key issues that should be considered to advance research in this area: (1) establish working mechanisms of the combination and contributions of each individual compound; (2) validate the relevance of the mechanisms for the targeted human condition; (3) include current nutrient status, intake or dietary pattern as inclusion/exclusion criteria in the study design; (4) select a participant population that is clinically and biologically appropriate for all nutritional components of the combination; (5) consider a range of cognitive outcomes; (6) consider the limits of reductionism and the ‘gold standard’ randomised controlled trial. These guiding principles will enhance our understanding of the interactive/complementary activities of dietary components, thereby strengthening the evidence base for recommendations aimed at delaying cognitive decline.

Background: Novel, less-invasive technologies to screen for Barrett's esophagus (BE) may enable a paradigm shift in early detection strategies for esophageal adenocarcinoma (EAC). Understanding professionals' perspectives on screening is important to determine how to proceed. We aimed to explore and compare professionals' perceptions of screening for BE and EAC screening in three countries., Methods: In this study, 29 Dutch, 20 British and 18 American health care professionals (clinicians, researchers and policy makers) participated in concept mapping: a mixed-methods consensus building methodology. Statements on perceived barriers, facilitators, advantages, disadvantages, implications or worries associated with screening for BE and EAC were collected in asynchronous digital brainstorm sessions. Subsequently, participants sorted the statements into groups according to thematic similarity and assessed the relevance of each statement in evaluating the acceptability of BE and EAC screening. Multidimensional scaling and cluster analysis were used to map the associations between generated statements., Results: Professionals across three countries identified eight consistent themes that relate to their perceptions of screening for BE and EAC: (1) Benefits, (2) Harms, (3) Clinical effectiveness concerns, (4) Screening population, (5) Screening modality, (6) Resources, (7) Ownership, and (8) Public communication. Dutch and American professionals prioritized the potential health benefits of screening but also questioned clinical impact. In contrast, British participants prioritized identification of the screening population and suitable test., Conclusions: Most professionals see potential in less-invasive screening tests for BE and EAC but underline the need to define the target screening population and determine benefits and harms before widely employing them. Successful implementation will require thoughtful consideration of the involvement of general practitioners, readiness of endoscopy and pathology services, balanced public communication, and country-specific regulations., (© 2023. The Author(s).)

Background: Compared to the previous cytology-based program, the introduction of primary high-risk human papillomavirus (hrHPV) based screening in 2017 has led to an increased number of referrals. To counter this, triage of hrHPV-positive women in cervical cancer screening can potentially be optimized by taking sociodemographic and lifestyle risk factors for cervical abnormalities into account. Therefore, it is essential to gain knowledge of the views of women (30-60 years) eligible for cervical cancer screening., Objective: The main goal of this qualitative study was to gain insight in the aspects that influence acceptability of risk-based triage in cervical cancer screening., Design: A focus group study in which participants were recruited via four general medical practices, and purposive sampling was used to maximize heterogeneity with regards to age, education level, and cervical cancer screening experiences., Approach: The focus group discussions were transcribed verbatim and analyzed using reflexive thematic analysis., Participants: A total of 28 women (average age: 45.2 years) eligible for cervical cancer screening in The Netherlands participated in seven online focus group discussions. Half of the participants was higher educated, and the participants differed in previous cervical cancer screening participation and screening result., Key Results: In total, 5 main themes and 17 subthemes were identified that determine the acceptability of risk-stratified triage. The main themes are: 1) adequacy of the screening program: an evidence-based program that is able to minimize cancer incidence and reduce unnecessary referrals; 2) personal information (e.g., sensitive topics and stigma); 3) emotional impact: fear and reassurance; 4) communication (e.g., transparency); and 5) autonomy (e.g., prevention)., Conclusion: The current study highlights several challenges regarding the development and implementation of risk-based triage that need attention in order to be accepted by the target group. These challenges include dealing with sensitive topics and a transparent communication strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Screening for early esophageal adenocarcinoma (EAC), including screening for its precursor Barrett's esophagus (BE), has the potential to reduce EAC-related mortality and morbidity. This literature review aimed to explore professionals' views on the justification for EAC screening. A systematic search of Ovid Medline, EMBASE, and PsycInfo, from January 1, 2000 to September 22, 2022, identified 5 original studies and 63 expert opinion articles reporting professionals' perspectives on EAC screening. Included articles were qualitatively analyzed using the framework method, which was deductively led by modernized screening principles. The analyses showed that many professionals are optimistic about technological advancements in BE detection and treatment. However, views on whether the societal burden of EAC merits screening were contradictory. In addition, knowledge of the long-term benefits and risks of EAC screening is still considered insufficient. There is no consensus on who to screen, how often to screen, which screening test to use, and how to manage non-dysplastic BE. Professionals further point out the need to develop technology that facilitates automated test sample processing and public education strategies that avoid causing disproportionately high cancer worry and social stigma. In conclusion, modernized screening principles are currently insufficiently fulfilled to justify widespread screening for EAC. Results from future clinical screening trials and risk prediction modeling studies may shift professionals' thoughts regarding justification for EAC screening., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JS, YP, LR, MG, and MB have no conflicts of interest or financial ties related to this work to disclose. PS is receiving unrestricted research grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China) and The eNose Company (Netherlands) and is in the advisory board of Motus GI (US) and Boston Scientific (US)., (© 2023 The Author(s).)

Objective: Screening for early oesophageal adenocarcinoma (OAC), including its precursor Barrett's oesophagus (BO), can potentially reduce OAC-related morbidity and mortality. This study explores Dutch at-risk individuals' views of screening an at-risk population for BO/OAC., Design: We invited 372 individuals with risk factors for OAC from primary care practices, 73 individuals with surveillance experience, and 221 participants of previous studies (BO/OAC screening trial or survey) to participate in focus groups. Transcripts were inductively and thematically analysed by two independent researchers., Results: A total of 50 individuals (42% with gastro-oesophageal reflux symptoms) of 50-75 years participated. Themes that were raised included: theme 1 'screening intentions' describing participants' motivation to be screened (eg, early diagnosis, potential reassurance, physician recommendation, and knowing someone with cancer) or decline screening (eg, anticipated discomfort or suboptimal accuracy of the test); theme 2 'risk-based eligibility' describing the tension between effectiveness (eg, targeting high-risk individuals) and inclusivity (eg, making screening available for everyone); theme 3 'distributive justice', in which the pressure of a potential new screening programme on healthcare resources was discussed; and theme 4 'information needs' describing the perceived lack of information access and individuals' preference to discuss screening with their general practitioner., Conclusion: Individuals not only expressed high willingness to be screened but also voiced the concern that a new screening programme may pressure limited healthcare resources. If implemented, it is crucial to develop educational materials that meet the public's information needs and explain the test procedures and eligibility criteria while avoiding stigmatising language., Competing Interests: Competing interests: PS is receiving unrestricted grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China), and The eNose Company (Netherlands) and is in the advisory board of Motus GI (USA) and Boston Scientific (USA)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Oesophageal adenocarcinoma (OAC) is increasingly diagnosed and often fatal, thus representing a growing global health concern. Screening for its precursor, Barrett's oesophagus (BO), combined with endoscopic surveillance and treatment of dysplasia might prevent OAC. This review aimed to systematically explore the public's acceptance and uptake of novel screening strategies for OAC. We systematically searched three electronic databases (Ovid Medline/PubMed, Ovid EMBASE and PsycINFO) from date of inception to July 2, 2021 and hand-searched references to identify original studies published in English on acceptability and uptake of OAC screening. Two reviewers independently reviewed and appraised retrieved records and two reviewers extracted data (verified by one other reviewer). Of the 3674 unique records, 19 studies with 15 249 participants were included in the review. Thematic analysis of findings showed that acceptability of OAC screening is related to disease awareness, fear, belief in benefit, practicalities and physical discomfort. The findings were mapped on the Integrated Screening Action Model. Minimally invasive screening tests are generally well-tolerated: patient-reported outcomes were reported for sedated upper endoscopy (tolerability ++), transnasal endoscopy (tolerability +), tethered capsule endomicroscopy (tolerability +/-), and the Cytosponge-TFF3 test (acceptability ++). In discrete choice experiments, individuals mainly valued screening test accuracy. OAC screening has been performed in trials using conventional upper endoscopy ( n  = 231 individuals), transnasal endoscopy ( n  = 966), capsule endoscopy ( n  = 657) and the Cytosponge-TFF3 test ( n  = 9679), with uptake ranging from 14·5% to 48·1%. Intended participation in OAC screening in questionnaire-based studies ranged from 62·8% to 71·4%. We conclude that the general public seems to have interest in OAC screening. The findings will provide input for the design of a screening strategy that incorporates the public's values and preferences to improve informed participation. Identification of a screening strategy effective in reducing OAC mortality and morbidity remains a crucial prerequisite., Funding: This study was funded by the Netherlands Organization for Health Research and Development (ZonMw) under grant 555,004,206., Competing Interests: PS is receiving unrestricted grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China) and The eNose Company (Netherlands) and is in the advisory board of Motus GI (USA) and Boston Scientific (USA). All other authors declare no competing interests., (© 2022 The Author(s).)

Purpose: Clinical evidence regarding optimal radiation dose for palliation of dysphagia from esophageal cancer is generally lacking. In an effort to investigate optimal radiation dose, we assessed 2 different radiation schedules for palliation of dysphagia., Methods and Materials: We performed a multicenter, retrospective study comparing low-dose radiation therapy (LR: 5 x 4 Gy external beam radiation therapy [EBRT]) with high-dose radiation therapy (HR: 10 x 3 Gy EBRT and 12-Gy single-dose intraluminal brachytherapy) for palliation of dysphagia in patients with inoperable or metastasized esophageal cancer. Primary outcome was improvement of dysphagia at 6 weeks after start of radiation therapy. Additional outcomes were persistent and recurrent dysphagia during patients' remaining life, severe adverse events, and survival., Results: In total, 292 patients (LR, n = 117; HR, n = 175) were included in this study. After matching, 144 patients (72 in each group) were compared. Improvement of dysphagia at 6 weeks was achieved in 50% of patients after LR and in 66% after HR (P = .071). Persistent or recurrent dysphagia occurred in 64% of patients after LR and in 42% after HR (P = .012). No difference in the rate of severe adverse events was found (P = .889). Median survival was 88 days (95% confidence interval, 64-112) after LR and 177 days (95% confidence interval, 131-223) after HR (P < .001)., Conclusions: This study shows that both LR and HR were well tolerated and effective in short-term relief of dysphagia in patients with inoperable or metastasized esophageal cancer. HR was associated with better long-term relief of dysphagia compared with LR. Our findings suggest that HR could be considered for patients with a longer life expectancy, but prospective studies are required., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic dilation (ED) is still the mainstay of therapeutic management of benign esophageal strictures (BESs). This study aimed to establish risk factors for refractory BESs and assess long-term clinical outcomes of ED., Methods: We performed a retrospective study in 891 patients who underwent ED from 2003 to 2018 for BESs. We searched electronic medical records in 6 tertiary care centers in the Netherlands for data on clinical outcome of ED. Median follow-up was 39 months. The primary endpoint was risk factors for refractory BESs, defined as factors associated with an increased number of ED sessions during follow-up. Secondary endpoints were time from first to last ED session and adverse events., Results: Dilation up to 13 to 15 mm was associated with a higher number of ED sessions than dilation up to 16 to 18 mm (5.0 vs 4.1; hazard ratio [HR], 1.4; P = .001). Compared with peptic strictures, anastomotic (4.9 vs 3.6; HR, 2.1; P < .001), radiation (5.0 vs 3.6; HR, 3.0; P < .001), caustic (7.2 vs 3.6; HR, 2.7; P < .001), and postendotherapy (3.9 vs 3.6; HR, 1.8; P = .005) strictures were associated with a higher number of ED sessions. After 1 year of follow-up, the proportions of patients who remained free of ED was 75% in anastomotic, 71% in radiation, 70% in peptic, 83% in postendotherapy, and 62% in caustic strictures. Esophageal perforation occurred in 23 ED sessions (.4%) in 22 patients (2.4%)., Conclusions: More than 60% of patients with BESs remain free of ED after 1 year of follow-up. Because dilation up to 16 to 18 mm diameter was associated with fewer ED sessions during follow-up, we suggest that clinicians should consider dilation up to at least 16 mm to reduce the number of ED sessions in these patients., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated., Objectives: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe)., Conclusion: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Intake of specific nutrients has been linked to mental states and various indices of cognitive performance although the effects are often subtle and difficult to interpret. Measurement of so-called objective variables (e.g. reaction times) is often considered to be the gold standard for assessing outcomes in this field of research. It can, however, be argued that data on subjective experience (e.g. mood) are also important and may enrich existing objective data. The aim of this review is to evaluate methods for measuring mental performance and mood, considering the definition of subjective mood and the validity of measures of subjective experience., Methods: A multi-stakeholder expert group was invited by ILSI Europe to come to a consensus around the utility of objective and subjective measurement in this field, which forms the basis of the paper. Therefore, the present review reflects a succinct overview of the science but is not intended to be a systematic review., Results: The proposed approach extends the traditional methodology using standard 'objective' measurements to also include the consumers' subjective experiences in relation to food. Specific recommendations include 1) using contemporary methods to capture transient mood states; 2) using sufficiently sensitive measures to capture effects of nutritional intervention; 3) considering the possibility that subjective and objective responses will occur over different time frames; and 4) recognition of the importance of expectancy and placebo effects for subjective measures., Conclusions: The consensus reached was that the most informative approach should involve collection and consideration of both objective and subjective data., Competing Interests: Compliance with ethical standardsConflict of interestC. Saunders is a full-time employee of PepsiCo Inc. J. Sijben is a full-time employee of Nutricia Research. E. Siobhan Mitchell is a full-time employee of Nestlé Institute of Health Sciences. S. Layé, E. Siobhan Mitchell and J. Schuermans have no competing interests. M. Hamer has received funding from industry for research on physical activity and well-being. L. Dye and N. Boyle have received funding from various food companies for contract research on the effects of food on cognitive function and mood.

Background: The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs., Objective: In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated., Methods: Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter., Results: Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention., Conclusion: Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

Accumulating evidence shows nutritional factors influence the risk of developing Alzheimer's disease (AD) and its rate of clinical progression. Dietary and lifestyle guidelines to help adults reduce their risk have been developed. However, the clinical dementia picture remains complex, and further evidence is required to demonstrate that modifying nutritional status can protect the brain and prevent, delay, or reduce pathophysiological consequences of AD. Moreover, there is a pressing need for further research because of the global epidemic of overweight and obesity combined with longer life expectancy of the general population and generally observed decreases in body weight with aging and AD. A new research approach is needed, incorporating more sophisticated models to account for complex scenarios influencing the relationship between nutritional status and AD. Systematic research should identify and address evidence gaps. Integrating longitudinal epidemiological data with biomarkers of disease, including brain imaging technology, and randomized controlled interventions may provide greater insights into progressive and subtle neurological changes associated with dietary factors in individuals at risk for or living with AD. In addition, greater understanding of mechanisms involved in nutritional influences on AD risk and progression, such as oxidative stress and loss of neuronal membrane integrity, will better inform possible interventional strategies. There is consensus among the authors that nutritional deficits, and even states of excess, are associated with AD, but more work is needed to determine cause and effect. Appropriately designed diets or nutritional interventions may play a role, but additional research is needed on their clinical-cognitive effectiveness.

Background: Alzheimer disease (AD) patients are at risk of nutritional insufficiencies because of physiological and psychological factors. Nutritional compounds are postulated to play a role in the pathophysiological processes that are affected in AD. We here provide the first systematic review and meta-analysis that compares plasma levels of micronutrients and fatty acids in AD patients to those in cognitively intact elderly controls. A secondary objective was to explore the presence of different plasma nutrient levels between AD and control populations that did not differ in measures of protein/energy nourishment., Methods: We screened literature published after 1990 in the Cochrane Central Register of Controlled Trials, Medline, and Embase electronic databases using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for AD patients, controls, micronutrient, vitamins, and fatty acids, resulting in 3397 publications, of which 80 met all inclusion criteria. Status of protein/energy malnutrition was assessed by body mass index, mini nutritional assessment score, or plasma albumin. Meta-analysis, with correction for differences in mean age between AD patients and controls, was performed when more than five publications were retrieved for a specific nutrient., Results: We identified five or more studies for folate, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E, copper, iron, and zinc but fewer than five studies for vitamins B1 and B6, long-chain omega-3 fatty acids, calcium, magnesium, manganese, and selenium (the results of the individual publications are discussed). Meta-analysis showed significantly lower plasma levels of folate and vitamin A, vitamin B12, vitamin C, and vitamin E (P < .001), whereas nonsignificantly lower levels of zinc (P = .050) and vitamin D (P = .075) were found in AD patients. No significant differences were observed for plasma levels of copper and iron. A meta-analysis that was limited to studies reporting no differences in protein/energy malnourishment between AD and control populations yielded similar significantly lower plasma levels of folate and vitamin B12, vitamin C, and vitamin E in AD., Conclusions: The lower plasma nutrient levels indicate that patients with AD have impaired systemic availability of several nutrients. This difference appears to be unrelated to the classic malnourishment that is well known to be common in AD, suggesting that compromised micronutrient status may precede protein and energy malnutrition. Contributing factors might be AD-related alterations in feeding behavior and intake, nutrient absorption, alterations in metabolism, and increased utilization of nutrients for AD pathology-related processes. Given the potential role of nutrients in the pathophysiological processes of AD, the utility of nutrition may currently be underappreciated and offer potential in AD management., (Copyright © 2014 The Alzheimer's Association. All rights reserved.)

The objective of the present study was to evaluate the effect of a paediatric tube feed supplemented with a multifibre mixture on the gut microbiota and nutritional and micronutrient status of children on long-term enteral nutrition (EN). A randomised, controlled, double-blind, cross-over trial (2 × 3 months) with a washout period of 1 month was carried out. Twenty-seven children (80% neurologically impaired) aged 11.9 (SD 3.9) years, on long-term EN (4.8 (SD 3.9) years) were recruited. The analyses of the children's faecal pH, microbiota along with anthropometric measures, bowel movements and markers of blood micronutrient status were made. Twenty children completed the study. A significant increase in the proportion of stool bifidobacteria (+16.6%, P < 0.05) was observed during the multifibre period than during the fibre-free period, together with a significant reduction in stool pH (P < 0.001). Stool frequency and consistency as well as growth did not differ between the two periods. There was a significant increase (P < 0.05) in plasma ferritin at the end of the fibre-free period, but plasma ferritin levels remained within normal ranges during both periods. No diet effects on other blood parameters were observed. In conclusion, addition of a multifibre mixture with prebiotic components to paediatric EN is well tolerated, promotes bifidobacteria and reduces stool pH, indicating an improved gut health.

1. Effects of linoleic and linolenic acid provided via different oil sources on total antibody (Ab) titres, Ab isotypes after primary and secondary immunisation, and cutaneous hypersensitivity (CH) responses to bovine serum albumin (BSA) and maleyl-BSA, respectively, were studied in pullets fed on one of 4 diets. The diets were the basal control diet enriched with either sunflower oil or safflower oil as sources of linoleic acid, and linseed oil as a source of linolenic acid, tested against a control diet supplemented with animal fat. 2. Total Ab and immunoglobulin (Ig) isotype responses to BSA were affected by diet after primary, and diet x immunisation effects after secondary immunisation. Higher total Ab and IgG titres to BSA were found especially after primary immunisation in birds given the sunflower oil enriched diet, whereas birds given sunflower oil mounted significantly lower IgM titres to BSA after primary and secondary immunisation. The antibody responses to maleyl-BSA were affected by diet after primary, and immunisation x diet interactions after secondary immunisation. Sunflower oil enhanced total and IgG Ab titres to maleyl-BSA after primary immunisation, but decreased IgM titres to maleyl-BSA after primary and secondary immunisation. Cutaneous hypersensitivity responses to BSA and maleyl-BSA were not affected by the diet. 3. It is concluded that modulation of the magnitude and isotype of Ab responses of poultry to T cell-dependent antigens is affected not only by type of essential fatty acids, but also by their source. In the present study the n-6 source, sunflower oil, showed strong enhancement of primary Ab responses, directed to both Th2 and Th1 antigens. On the other hand, the different effects of safflower oil imply that constituents other than n-6 acids within dietary plant oils may affect immune responsiveness. 4. The relationship between magnitude and isotype of Ab responsiveness, type of antigen, and essential fatty acids is discussed.

1. Effects of dietary polyunsaturated fatty acids (PUFA) and vitamin E (VE) on an immune response may interact because VE may protect PUFA from in vivo oxidation. The present study was designed to study the presence of such an interaction in growing layer chickens. 2. Three dietary concentration of linoleic acid (LA, 3.3, 6.6 and 10%), in combination with 4 concentration of dietary VE (5, 20, 40 and 80 mg/kg) were used. Effects of LA and VE on circulating VE concentration, fatty acid composition of bursal and adipose fat, and antibody kinetics against keyhole limpet hemocyanin and Mycobacterim butyricum were established. 3. At high dietary LA concentration, bursal and adipose LA were higher but bursal arachidonic acid and long chain n-3 PUFA decreased. The dietary VE level did not consistently affect the deposition of PUFA in tissue. Plasma VE concentrations were affected by the dietary VE and LA content, but not by their interaction. Antibody responses before and 7 d after immunisation were affected by the dietary treatments. Antibody concentration were not affected by tissue fatty acid content. 4. In conclusion, the interaction effects of dietary PUFA and VE on fat deposition and immune responses are of minor importance compared to separate PUFA and VE effects. This implies that, within the studied range, adding extra VE to preserve or affect the effects of dietary PUFA on antibody responsiveness is unnecessary.