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The prevalence of informal caregiving is increasing as populations across the world age. Caregiving has been found to be associated with poor mental health outcomes including depressive symptoms. The purpose of this study is to examine the mean trajectory of depressive symptomatology in older caregivers in a large European sample over an eight-year period, the effects of time-varying and time-invariant covariates on this trajectory, and the mean trajectory of depressive symptomatology according to pattern of caregiving. The results suggest that depressive symptoms in the full sample of caregivers follow a nonlinear trajectory characterized by an initial decrease which decelerates over time. Caregiver status and depressive symptoms were significantly associated such that depressive symptoms increased as a function of caregiver status. The trajectory in caregivers who report intermittent or consecutive occasions of caregiving remained stable over time. Significant associations were found between sociodemographic, health and caregiving characteristics and the initial levels and rates of change of these trajectories. While these results point to the resilience of caregivers, they also highlight the factors that are related to caregivers' adaptation over time. This can help in identifying individuals who may require greater supports and, in turn, ensuring that caregivers preserve their well-being. [ABSTRACT FROM AUTHOR]

Studies examining lifestyle and cognitive decline often use healthy lifestyle indices, making it difficult to understand implications for interventions. We examined associations of 16 lifestyles with cognitive decline. Data from 32,033 cognitively-healthy adults aged 50-104 years participating in prospective cohort studies of aging from 14 European countries were used to examine associations of lifestyle with memory and fluency decline over 10 years. The reference lifestyle comprised not smoking, no-to-moderate alcohol consumption, weekly moderate-plus-vigorous physical activity, and weekly social contact. We found that memory and fluency decline was generally similar for non-smoking lifestyles. By contrast, memory scores declined up to 0.17 standard deviations (95% confidence interval= 0.08 – 0.27) and fluency scores up to 0.16 standard deviations (0.07 – 0.25) more over 10 years for those reporting smoking lifestyles compared with the reference lifestyle. We thus show that differences in cognitive decline between lifestyles were primarily dependent on smoking status. Lifestyle may contribute to cognitive ageing. Here, the authors examine lifestyles comprised of smoking, drinking, physical activity, and social contact habits to show lifestyle differences in cognitive decline primarily depended on smoking habits. [ABSTRACT FROM AUTHOR]

Background: Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer's Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. Methods: We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task. Results: The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions. Conclusions: Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition. [ABSTRACT FROM AUTHOR]

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs. [ABSTRACT FROM AUTHOR]

The study of the nutritional status is relevant during the entire life course, but in children it is relevant as malnutrition may be a marker of underlying functional and mental health deficits. Evidence of the association between malnutrition and school dropout is not conclusive. Our aim was to analyze children's nutritional trajectory measured using their Body Mass Index (BMI) of a Uruguayan cohort and its association with school dropout. With this purpose, Latent Class and Joint Latent Class Mixed Models were fitted to children's cohort study (N = 1392 girls and 1492 boys) in sex-stratified analyses adjusting for sociodemographic characteristics. We identified latent classes of boys and girls with similar BMI trajectories during school years and differences in relevant socioeconomic and anthropometric characteristics. Results indicated that boys dropped out at younger ages than girls. No association between age of school dropout and nutritional trajectory classes was found. None of the classes exhibited a deficit or decrease in BMI trajectories during school ages, although the obesity and overweight classes could be of concern. Results suggested no significant association between obesity or overweight and age of school dropout for children up to 14 years old. Future research on other samples may inform about trajectories in higher educational levels. [ABSTRACT FROM AUTHOR]

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health. Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, blood protein markers of brain health are integrated with omics data to reveal DNA methylation differences that associate with these protein markers. [ABSTRACT FROM AUTHOR]

Background: Macrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer's disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the association of midlife dementia risk with brain macrostructural alterations. Methods: Structural 3T MRI scans were acquired for 647 cognitively normal middle-aged (40–59 years old) participants in the PREVENT-Dementia study. Cortical thickness, volumes of subcortical structures, the hippocampus and hippocampal subfields were quantified using Freesurfer version 7.1. The clarity of the hippocampal molecular layer was evaluated based on T2-weighted hippocampal scans. Associations of structural measures with apolipoprotein ε4 (APOE4) genotype and dementia family history (FHD), were investigated using linear regression. Correlations between the CAIDE dementia risk score (incorporating information about blood pressure, cholesterol, physical activity, body mass index, education, age and sex) and structural measures were further investigated. Results: A higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity. Conclusions: Our findings suggest that a higher CAIDE score is associated with widespread cortical thinning. Conversely, APOE4 carriers and participants with FHD do not demonstrate prominent macrostructural alterations at this age range. These findings indicate that cardiovascular and not inherited risk factors for dementia are associated with macrostructural brain alterations at midlife. [ABSTRACT FROM AUTHOR]

Background: Structural brain changes associated with Alzheimer's disease (AD) can occur decades before the onset of symptoms. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score has been suggested to be associated with accelerated brain atrophy in middle-aged subjects but the regional specificity of atrophic areas remains to be elucidated. Methods: 3T T1-weighted magnetic resonance imaging scans of 160 cognitively healthy middle-aged participants (mean age = 52) in the PREVENT-Dementia cohort, from baseline and from follow-up after 2 years, were examined. Images were preprocessed using Computational Anatomy Toolbox 12. Voxel-based morphometry was performed in FSL 6.0.1 to identify areas of grey matter (GM) volume differences both cross-sectionally and longitudinally between subjects with high and low baseline CAIDE score (CAIDE score was dichotomized at cohort-median). A GM percentage of change map was created for each subject for evaluation of atrophy over 2 years. Analyses were adjusted for age, gender, education and total intracranial volume. Results: Compared to subjects with CAIDE score ≤ 6 (low risk), subjects with CAIDE score > 6 (high risk) showed lower GM volume in the temporal, occipital, and fusiform cortex and lingual gyrus at baseline, and greater percentage of GM loss over 2 years in the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus (corrected P < 0.05). Conclusion: This study demonstrated accelerated GM atrophy concentrated in several AD signature cortical regions in healthy middle-aged subjects with high CAIDE scores. [ABSTRACT FROM AUTHOR]

A model is presented that describes bivariate longitudinal count data by conditioning on a progressive illness-death process where the two living states are latent. The illness-death process is modelled in continuous time, and the count data are described by a bivariate extension of the binomial distribution. The bivariate distributions for the count data approach include the correlation between two responses even after conditioning on the state. An illustrative data analysis is discussed, where the bivariate data consist of scores on two cognitive tests, and the latent states represent two stages of underlying cognitive function. By including a death state, possible association between cognitive function and the risk of death is accounted for. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine factors associated with a prolonged length of stay (LOS) in patients over 75 undergoing a total knee replacement (TKR). Methods: Patients over 75 undergoing a TKR at our institution from January 2008 to February 2009 were identified ( n = 112). Patient and operative factors previously shown to affect length of stay were identified. Patient notes were reviewed for details on each of these and data analysed for their effect on length of stay. Discrete data were analysed for their effect on post-operative length of stay using either the Mann-Whitney U test or the Kruskall-Wallis test and continuous data analysed with the Spearman's rank correlation coefficient. Results: The following factors were associated with length of stay at the 95 % confidence level: patient age, pre-operative mobility and the use of walking aids, BMI, whether the patient was able to mobilise within 24 or 48 hours of the surgery, the day on which the patient first walked ten metres and achieved 90° active knee flexion, pre and post-operative haemoglobin and the need for a blood transfusion. Conclusions: Pre-operative use of walking aids, peri-operative haemoglobin concentration, failure to mobilise early following the operation and post-operative complications (including the need for a blood transfusion) seem to be the significant factors associated with a prolonged stay in hospital in the over 75 year olds. [ABSTRACT FROM AUTHOR]