The use of canonical correlation analysis to assess the relationship between executive functioning and verbal memory in older adults

Executive functioning (EF), which is considered to govern complex cognition, and verbal memory (VM) are constructs assumed to be related. However, it is not known the magnitude of the association between EF and VM, and how sociodemographic and psychological factors may affect this relationship, including in normal aging. In this study, we assessed different EF and VM parameters, via a battery of neurocognitive/psychological tests, and performed a Canonical Correlation Analysis (CCA) to explore the connection between these constructs, in a sample of middle- aged and older healthy individuals without cognitive impairment (N = 563, 50+ years of age). The analysis revealed a positive and moderate association between EF and VM independently of gender, age, education, global cognitive performance level, and mood. These results confirm that EF presents a significant association with VM performance.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). P.S.M. is supported by a “MyHealth” project (Contract DoIT-13853) doctoral fel- lowship and N.C.S. by a “SwitchBox” project post-doctoral fellowship

Telephone-based screening tools for mild cognitive impairment and dementia in aging studies : a review of validated instruments

The decline of cognitive function in old age is a great challenge for modern society. The simultaneous increase in dementia and other neurodegenerative diseases justifies a growing need for accurate and valid cognitive assessment instruments. Although in-person testing is considered the most effective and preferred administration mode of assessment, it can pose not only a research difficulty in reaching large and diverse population samples, but it may also limit the assessment and follow-up of individuals with either physical or health limitations or reduced motivation. Therefore, telephone-based cognitive screening instruments can be an alternative and attractive strategy to in-person assessments. In order to give a current view of the state of the art of telephone-based tools for cognitive assessment in aging, this review highlights some of the existing instruments with particular focus on data validation, cognitive domains assessed, administration time and instrument limitations and advantages. From the review of the literature, performed using the databases EBSCO, Science Direct and PubMed, it was possible to verify that while telephone-based tools are useful in research and clinical practice, providing a promising approach, the methodologies still need refinement in the validation steps, including comparison with either single instruments or neurocognitive test batteries, to improve specificity and sensitivity to validly detect subtle changes in cognition that may precede cognitive impairment.This work was funded by the European Commission (FP7): "SwitchBox" (Contract HEALTH-F2-2010-259772). Teresa C. Castanho and Liliana Amorim are recipients of doctoral fellowships from the Fundacao para a Ciencia e Tecnologia (FCT, Portugal) and the MyHealth project (Contract DoIT-13853), respectively. Nadine C. Santos is a recipient of a postdoctoral fellowship by the Switchbox project

The use of multiple correspondence analysis to explore associations between categories of qualitative variables in healthy ageing

In pressPopulation studies are often characterized by a plethora of data that includes quantitative to qualitative variables. The main focus of this study was to illustrate the applicability of multiple correspondence analysis (MCA) in detecting and representing underlying structures in large datasets used to investigate cognitive ageing. Principal component analysis (PCA) was used to obtain main cognitive dimensions (based on the continuous neurocognitive test variables) and MCA to detect and explore relationships of cognitive, clinical, physical and lifestyle categorical variables across the low-dimensional space. Altogether the technique allows to not only simplify complex data, providing a detailed description of the data and yielding a simple and exhaustive analysis, but also to handle a large and diverse dataset comprised of quantitative, qualitative, objective and subjective data. Two PCA dimensions were identified (general cognition/executive function and memory) and two main MCA dimensions were retained. As expected, poorer cognitive performance was associated with older age, less school years, unhealthier lifestyle indicators and presence of pathology. Interestingly, the first MCA dimension indicated the clustering of general/executive function and lifestyle indicators and education, while the second association between memory and clinical parameters and age. The clustering analysis with object scores method was used to identify groups sharing similar characteristics within each of the identified dimensions. Following MCA findings, the weaker cognitive clusters in terms of memory and executive function comprised individuals with characteristics contributing to a higher MCA dimensional mean score (age, less education and presence of indicators of unhealthier lifestyle habits and/or clinical pathologies). MCA provided a powerful tool to explore complex ageing data, covering multiple and diverse variables, showing not only if a relationship exists between variables but also how they are related, offering at the same time statistical results can be seen both analytically and visually.EC -European Commissio

Discriminant power of socio-demographic characteristics and mood in distinguishing cognitive performance clusters in older individuals: a cross-sectional analysis

Objectives: Identification of predictors of cognitive trajectories has been a matter of concern on aging research. For this reason, it is of relevance to infer cognitive profiles based on rapid screening variables in order to determine which individuals will be more predisposed to cognitive decline. Method: In this work, a linear discriminant analysis (LDA) was conducted with socio-demographic variables and mood status as predictors of cognitive profiles, computed in a previous sample, based on different cognitive dimensions. Data were randomly split in two samples. Both samples were representative of the Portuguese population in terms of gender, age and education. The LDA was performed with one sample (n D 506, mean age 65.7 § 8.98 years) and tested in the second sample (n = 548, mean age 68.5 § 9.3 years). Results: With these variables, we were able to achieve an overall hit rate of 65.9%, which corresponds to a significant increment in comparison to classification by chance. Conclusion: Although not ideal, this model may serve as a relevant tool to identify cognitive profiles based on a rapid screening when few variables are available.European Commission (FP7): ‘SwitchBox’ [contract number HEALTH-F22010-259772]; Portuguese North Regional Operational Program (ON.2 O Novo Norte) under the National Strategic Reference Framework (QREN); European Regional Development Fund (FEDER).info:eu-repo/semantics/publishedVersio

Adult body height is a good predictor of different dimensions of cognitive function in aged individuals: a cross-sectional study

Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals. Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors (gender, age, school years, physical activity, alcohol consumption, and smoking habits). We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function (beta, = 0.139; p < 0.001) and memory (beta = 0.099; p 0.05). No relation was found between mood and any of the anthropometric measures studied. Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance.European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772) project 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), and by Fundação Calouste Gulbenkian—Inovar em Saúde (“Envelhecimento cognitivo saudável—proporcionar saúde mental no processo biológico do envelhecimento,” Contract P-139977). NCS is supported by a SwitchBox post-doctoral fellowshi

Effector memory CD4+ T cells are associated with cognitive performance in a senior population

Objective: Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. Methods: In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Results: Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account. Conclusions: This is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.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)

Exploring the factor structure of neurocognitive measures in older individuals

Here we focus on factor analysis from a best practices point of view, by investigating the factor structure of neuropsychological tests and using the results obtained to illustrate on choosing a reasonable solution. The sample (n=1051 individuals) was randomly divided into two groups: one for exploratory factor analysis (EFA) and principal component analysis (PCA), to investigate the number of factors underlying the neurocognitive variables; the second to test the "best fit" model via confirmatory factor analysis (CFA). For the exploratory step, three extraction (maximum likelihood, principal axis factoring and principal components) and two rotation (orthogonal and oblique) methods were used. The analysis methodology allowed exploring how different cognitive/psychological tests correlated/discriminated between dimensions, indicating that to capture latent structures in similar sample sizes and measures, with approximately normal data distribution, reflective models with oblimin rotation might prove the most adequate.The study is integrated in the ‘‘Maintaining health in old age through homeostasis (SWITCHBOX)’’ (http://www.switchbox-online.eu/) collaborative project funded by the European Commission FP7 initiative (grant 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). NCS is supported by a SwitchBox post-doctoral fellowship, LA and PSM are supported by "MyHealth” project (Contract DoIT-13853)" doctoral fellowships

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

Clinical, physical and lifestyle variables and relationship with cognition and mood in aging: a cross-sectional analysis of distinct educational groups

It is relevant to unravel the factors that may mediate the cognitive decline observed during aging. Previous reports indicate that education has a positive influence on cognitive performance, while age, female gender and, especially, depressed mood were associated with poorer performances across multiple cognitive dimensions (memory and general executive function). Herein, the present study aimed to characterize the cognitive performance of community-dwelling individuals within distinct educational groups categorized by the number of completed formal school years: "less than 4," "4, completed primary education," and "more than 4." Participants (n = 1051) were randomly selected from local health registries and representative of the Portuguese population for age and gender. Neurocognitive and clinical assessments were conducted in local health care centers. Structural equation modeling was used to derive a cognitive score, and hierarchical linear regressions were conducted for each educational group. Education, age and depressed mood were significant variables in directly explaining the obtained cognitive score, while gender was found to be an indirect variable. In all educational groups, mood was the most significant factor with effect on cognitive performance. Specifically, a depressed mood led to lower cognitive performance. The clinical disease indices cardiac and stroke associated with a more negative mood, while moderate increases in BMI, alcohol consumption and physical activity associated positively with improved mood and thus benefitted cognitive performance. Results warrant further research on the cause-effect (longitudinal) relationship between clinical indices of disease and risk factors and mood and cognition throughout aging.This work was funded by the European Commission (FP7): "SwitchBox" (Contract HEALTH-F2-2010-259772). Nadine C. Santos is supported by a SwitchBox post-doctoral fellowship; Carlos Portugal-Nunes and Liliana Amorim by a MyHealth (DoIT-Desenvolvimento e Operacionalizacao da Investigacao de Translacao, Contract 13853) research and PhD fellowships, respectively. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation. We thank Dr. Matthew Stump and Daniel Zimmerman for the careful reading of the manuscript

Stress impact on resting state brain networks

Resting state brain networks (RSNs) are spatially distributed large-scale networks, evidenced by resting state functional magnetic resonance imaging (fMRI) studies. Importantly, RSNs are implicated in several relevant brain functions and present abnormal functional patterns in many neuropsychiatric disorders, for which stress exposure is an established risk factor. Yet, so far, little is known about the effect of stress in the architecture of RSNs, both in resting state conditions or during shift to task performance. Herein we assessed the architecture of the RSNs using functional magnetic resonance imaging (fMRI) in a cohort of participants exposed to prolonged stress (participants that had just finished their long period of preparation for the medical residence selection exam), and respective gender- and age-matched controls (medical students under normal academic activities). Analysis focused on the pattern of activity in resting state conditions and after deactivation. A volumetric estimation of the RSNs was also performed. Data shows that stressed participants displayed greater activation of the default mode (DMN), dorsal attention (DAN), ventral attention (VAN), sensorimotor (SMN), and primary visual (VN) networks than controls. Importantly, stressed participants also evidenced impairments in the deactivation of resting state-networks when compared to controls. These functional changes are paralleled by a constriction of the DMN that is in line with the pattern of brain atrophy observed after stress exposure. These results reveal that stress impacts on activation-deactivation pattern of RSNs, a finding that may underlie stress-induced changes in several dimensions of brain activity.JMS, NCS and PM are supported by fellowships of the project SwitchBox-FP7-HEALTH-2010-grant 259772-2; FM is supported by the fellowship SFRH/BPD/33379/2008 funded by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal). The work was supported by SwitchBox-FP7-HEALTH-2010-grant 259772-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript