Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia

Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia.Nadine C. Santos and Fernanda Marques are recipients of postdoctoral fellowships by the Switchbox project (European Commission FP7 initiative grant HEALTH-F2-2010-259772) and the Fundação para a Ciência e Tecnologia (FCT, Portugal), respectively

Modulation of iron metabolism in aging and in Alzheimer's disease: relevance of the choroid plexus

Iron is essential for mammalian cellular homeostasis. However, in excess, it promotes free radical formation and is associated with aging-related progressive deterioration and with neurodegenerative disorders such as Alzheimer's disease (AD). There are no mechanisms to excrete iron, which makes iron homeostasis a very tightly regulated process at the level of the intestinal absorption. Iron is believed to reach the brain through receptor-mediated endocytosis of iron-bound transferrin by the brain barriers, the blood-cerebrospinal fluid (CSF) barrier, formed by the choroid plexus (CP) epithelial cells and the blood-brain barrier (BBB) formed by the endothelial cells of the brain capillaries. Importantly, the CP epithelial cells are responsible for producing most of the CSF, the fluid that fills the brain ventricles and the subarachnoid space. Recently, the finding that the CP epithelial cells display all the machinery to locally control iron delivery into the CSF may suggest that the general and progressive senescence of the CP may be at the basis of the impairment of regional iron metabolism, iron-mediated toxicity, and the increase in inflammation and oxidative stress that occurs with aging and, particularly, in AD.Sandro D. Mesquita and Ana C. Ferreira are recipients of fellowships from the Fundação para a Ciência e Tecnologia (FCT, Portugal). Fernanda Marques and Nadine C. Santos are recipients of postdoctoral fellowships by the Fundação para a Ciência e Tecnologia (FCT, Portugal) and the Switchbox project (European Commission FP7 initiative grant HEALTH-F2-2010-259772), respectively

Physical Activity and Nutrition INfluences In ageing (PANINI): consortium mission statement

First paragraph: Current demographic trends indicate that by the year 2020, almost one in five of the European population will be aged 65 years or over. Although life expectancy is increasing by 2 years per decade, the period of life spent in good health is not keeping pace and most Europeans spend their last decade in poor health. Consequently, there is an urgent need to understand how lifestyle factors can influence age-related changes from gene to society level and how they may be integrated into a net effect of healthy ageing. It is also crucial to develop and validate interventions and health policies to ensure that more of our older adults have a healthy and active later life. This is an urgent and cross-cutting research priority in Europe, and to achieve this, it is vital to increase research capacity in this area to push forward the frontiers of scientific understanding. The Horizon 2020 funded Marie Curie Sklodowska Innovative Training Network—PANINI is addressing this capacity issue by focusing on research and training in two major interacting lifestyle factors with impact at multiple levels, namely, physical activity and nutrition

Functional Hemispheric (A)symmetries in the Aged Brain-Relevance for Working Memory

Functional hemispheric asymmetries have been described in different cognitive processes, such as decision-making and motivation. Variations in the pattern of left/right activity have been associated with normal brain functioning, and with neuropsychiatric diseases. Such asymmetries in brain activity evolve throughout life and are thought to decrease with aging, but clear associations with cognitive function have never been established. Herein, we assessed functional laterality during a working memory task (N-Back) in a healthy aging cohort (over 50 years old) and associated these asymmetries with performance in the test. Activity of lobule VI of the cerebellar hemisphere and angular gyrus was found to be lateralized to the right hemisphere, while the precentral gyrus presented left > right activation during this task. Interestingly, 1-Back accuracy was positively correlated with left > right superior parietal lobule activation, which was mostly due to the influence of the left hemisphere. In conclusion, although regions were mostly symmetrically activated during the N-Back task, performance in working memory in aged individuals seems to benefit from lateralized involvement of the superior parietal lobule.NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and was funded by the European Commission (FP7) “SwitchBox—Maintaining health in old age through homeostasis” (Seventh Framework Programme; Contract HEALTH-F2-2010-259772), by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and by National Funds, through the Foundation for Science and Technology (FCT) under the scope of the project POCI-01-0145-FEDER-007038, by the Fundação Calouste Gulbenkian (Portugal; Contract Grant No: P-139977; project “TEMPO—Better mental health during ageing based on temporal prediction of individual brain ageing trajectories”) and by “PANINI—Physical Activity and Nutrition Influences In Ageing” (European Commission (Horizon 2020), Contract GA 675003); Fundação para a Ciência e a Tecnologia (FCT) (Grant Nos. SFRH/BD/52291/2013 to ME and PD/BD/106050/2015 to CP-N via Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC), SFRH/BPD/80118/2011 to HL-A and SFRH/BD/90078/2012 to TCC); and FCT/MEC and ON.2–ONOVONORTE—North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER (project FCTANR/NEU-OSD/0258/2012 to RM)info:eu-repo/semantics/publishedVersio

Brain structure across the lifespan : the influence of stress and mood

Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood, and their interplay in the brain gray and white matter (WM) structure. We showed the critical impact of age in the WM volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.We are thankful to all study participants. This work was funded by the European Commission (FP7): "SwitchBox" (Contract HEALTH-F2-2010-259772) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Jose M. Soares, Paulo Marques, and Nadine C. Santos are supported by fellowships of the project "SwitchBox"; Ricardo Magalhaes is supported by a fellowship from the project FCTANR/NEU-OSD/0258/2012 funded by FCT/MEC (www.fct.pt) and by ON.2 - ONOVONORTE - North - Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER

Risk and clinical-outcome indicators of delirium in an emergency department intermediate care unit (EDIMCU) : an observational prospective study

We are thankful to the staff at the EDIMCU of Hospital de Braga.Background Identification of delirium in emergency departments (ED) is often underestimated; within EDs, studies on delirium assessment and relation with patient outcome in Intermediate Care Units (IMCU) appear missing in European hospital settings. Here we aimed to determine delirium prevalence in an EDIMCU (Hospital de Braga, Braga, Portugal) and assessed routine biochemical parameters that might be delirium indicators. Methods The study was prospective and observational. Sedation level was assessed via the Richmond Agitation-Sedation Scale and delirium status by the Confusion Assessment Method for the ICU. Information collected included age and gender, admission type, Charlson Comorbidity Index combined condition score (Charlson score), systemic inflammatory response syndrome criteria (SIRS), biochemical parameters (blood concentration of urea nitrogen, creatinine, hemoglobin, sodium and potassium, arterial blood gases, and other parameters as needed depending on clinical diagnosis) and EDIMCU length of stay (LOS). Statistical analyses were performed as appropriate to determine if baseline features differed between the ‘Delirium’ and ‘No Delirium’ groups. Multivariate logistic regression was performed to assess the effect of delirium on the 1-month outcome. Results Inclusion and exclusion criteria were met in 283 patients; 238 were evaluated at 1-month for outcome follow-up after EDIMCU discharge (“good” recovery without complications requiring hospitalization or institutionalization; “poor” institutionalization in permanent care-units/assisted-living or death). Delirium was diagnosed in 20.1% patients and was significantly associated with longer EDIMCU LOS. At admission, Delirium patients were significantly older and had significantly higher blood urea, creatinine and osmolarity levels and significantly lower hemoglobin levels, when compared with No Delirium patients. Delirium was an independent predictor of increased EDIMCU LOS (odds ratio 3.65, 95% CI 1.97-6.75) and poor outcome at 1-month after discharge (odds ratio 3.51, CI 1.84-6.70), adjusted for age, gender, admission type, presence of SIRS criteria, Charlson score and osmolarity at admission. Conclusions In an EDIMCU setting, delirium was associated with longer LOS and poor outcome at1-month post-discharge. Altogether, findings support the need for delirium screening and management in emergency settings.NCS is supported by the post-doctoral fellowship UMINHO/BPD/013/2011 by the European Commission (FP7) “SwitchBox” Project (Contract HEALTH-F2-2010-259772)

The use of Bayesian latent class cluster models to classify patterns of cognitive performance in healthy ageing

The main focus of this study is to illustrate the applicability of latent class analysis in the assessment of cognitive performance profiles during ageing. Principal component analysis (PCA) was used to detect main cognitive dimensions (based on the neurocognitive test variables) and Bayesian latent class analysis (LCA) models (without constraints) were used to explore patterns of cognitive performance among community-dwelling older individuals. Gender, age and number of school years were explored as variables. Three cognitive dimensions were identified: general cognition (MMSE), memory (MEM) and executive (EXEC) function. Based on these, three latent classes of cognitive performance profiles (LC1 to LC3) were identified among the older adults. These classes corresponded to stronger to weaker performance patterns (LC1>LC2>LC3) across all dimensions; each latent class denoted the same hierarchy in the proportion of males, age and number of school years. Bayesian LCA provided a powerful tool to explore cognitive typologies among healthy cognitive agers.The study is integrated in the "Maintaining health in old age through homeostasis (SWITCHBOX)" collaborative project funded by the European Commission FP7 initiative (grant HEALTH-F2-2010-259772). NS and JAP are main team members of the European consortium SWITCHBOX (http://www.switchbox-online.eu/). NCS is supported by a SwitchBox post-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Physical Activity and Nutritional INfluences in Ageing (PANINI) Toolkit: A Standardized Approach towards Physical Activity and Nutritional Assessment of Older Adults

Assessing multiple domains of health in older adults requires multidimensional and large datasets. Consensus on definitions, measurement protocols and outcome measures is a prerequisite. The Physical Activity and Nutritional INfluences In Ageing (PANINI) Toolkit aims to provide a standardized toolkit of best-practice measures for assessing health domains of older adults with an emphasis on nutrition and physical activity. The toolkit was drafted by consensus of multidisciplinary and pan-European experts on ageing to standardize research initiatives in diverse populations within the PANINI consortium. Domains within the PANINI Toolkit include socio-demographics, general health, nutrition, physical activity and physical performance and psychological and cognitive health. Implementation across various countries, settings and ageing populations has proven the feasibility of its use in research. This multidimensional and standardized approach supports interoperability and re-use of data, which is needed to optimize the coordination of research efforts, increase generalizability of findings and ultimately address the challenges of ageing

Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis

First Online: 06 October 2012Identification of predictors of cognitive trajectories through the establishment of composite or single-parameter dimensional categories of cognition and mood may facilitate development of strategies to improve quality of life in the elderly. Participants (n = 487, aged 50+ years) were representative of the Portuguese population in terms of age, gender, and educational status. Cognitive and mood profiles were established using a battery of neurocognitive and psychological tests. Data were subjected to principal component analysis to identify core dimensions of cognition and mood, encompassing multiple test variables. Dimensions were correlated with age and with respect to gender, education, and occupational status. Cluster analysis was applied to isolate distinct patterns of cognitive performance and binary logistic regression models to explore interrelationships between aging, cognition, mood, and socio-demographic characteristics. Four main dimensions were identified: memory, executive function, global cognitive status, and mood. Based on these, strong and weak cognitive performers were distinguishable. Cluster analysis revealed further distinction within these two main categories into very good, good, poor, and very poor performers. Mood was the principal factor contributing to the separation between very good and good, as well as poor and very poor, performers. Clustering was also influenced by gender and education, albeit to a lesser extent; notably, however, female gender × lower educational background predicted significantly poorer cognitive performance with increasing age. Mood has a significant impact on the rate of cognitive decline in the elderly. Gender and educational level are early determinants of cognitive performance in later life.This work was funded by the European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772). NCS is supported by a SwitchBox post-doctoral fellowship. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation

El grupu neandertal de la Cueva d' El Sidrón (Borines, Piloña)

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