Early parental death and psychosocial risk factors for dementia: A case-control study in Europe

Objectives: To assess the association between early parental death and the risk of dementia in adult life, and to examine the risk factors associated with early parental death in people with and without dementia. Methods / Design: A population-based case-control study of a sample of 65,997 participants from the Survey of Health, Ageing and Retirement in Europe study. Early parental death was operationalized as parental death at the age of ≤ 16 years. Main analyses were conducted using bivariate and multivariate logistic regression analyses. Results: The odds ratio (OR) for dementia in individuals who experienced early parental death (father or mother) at the age of ≤ 16 years was 1.83 (95%CI 1.61-2.09) and 1.54 (95%CI 1.35-1.76) adjusted for age, gender, and education. In the multivariate logistic regression analysis carried out with the whole sample, early parental death increased the risk of dementia (OR = 1.50, 95%CI 1.31-1.72), along with older age (OR = 5.92, 95%CI 4.86-7.17), neuroticism (OR = 2.94,95%CI 2.61-3.31), low education level (OR = 1.84, 95%CI 1.64- 2.05) and low income (OR = 1.49, 95%CI 1.34-1.67). Discussion: Early parental death (< 16 years) was associated with an increased risk of dementia. We discuss the neurobiological markers associated with adverse childhood experiences (ACEs) and dementia as well as interventions to counteract the negative health effects on adults

Causes, mortality rates and risk factors of death in community-dwelling Europeans aged 50 years and over: Results from the Survey of Health, Ageing and Retirement in Europe 2013-2015

Objective: To determine mortality rates and to rank the causes and predictors of mortality using a wide range of sociodemographic and clinical variables. Materials and Methods: It is a prospective population-based cohort study of adults living in the community, 2013-15 (N = 48,691, age ≥50; deceased = 1,944). Clinical and sociodemographic data were obtained from the Survey of Health, Ageing and Retirement in Europe (SHARE): Age, Gender, Marital Status, Years of Schooling, Income, Loneliness, Cognition, Self-Rated Health, Diseases, Activities of daily living (ADL), Frailty and Mobility. Mortality rates were calculated. A Cox proportional hazards model were used to determine risk-adjusted mortality ratios with confidence intervals (99% CI). Results: The crude mortality rate was 18.39 (1000 person-years at risk), (99% CI, 18.37-18.42). The factors most associated with an increased mortality risk were older age, lower self-rated health, lower cognition, male gender, ADL deficits, higher comorbidity, frailty and loneliness. The diseases with a higher mortality risk were: cancer (Hazard ratio, HR = 2.67), dementia (HR = 2.19), depressive symptoms (HR = 2.10), fractures (hip, femur) (HR = 1.57), stroke (HR = 1.55), chronic lung disease (HR = 1.52), diabetes (HR = 1.36) and heart attack (HR = 1.21). Conclusions: The main mortality risk factors, associated independently in the eight diseases were: older age, poor self-rated health, ADL deficits, male gender, lower cognition, comorbidity and the presence of depressive symptoms. The need to evaluate and treat the depressive symptoms that accompanies diseases with higher risk of mortality is stressed

Microbiota alterations in proline metabolism impact depression

The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including patients with mild depression. Microbial functions and metabolites converging onto glutamate/GABA metabolism, particularly proline, were linked to depression. High proline consumption was the dietary factor with the strongest impact on depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotionally impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related prefrontal cortex genes. RNAi-mediated knockdown of proline and GABA transporters in Drosophila and mono-association with L. plantarum, a high GABA producer, conferred protection against depression-like states. Targeting the microbiome and dietary proline may open new windows for efficient depression treatment

Real-world evidence in Alzheimer’s disease: the ROADMAP Data Cube

INTRODUCTION:The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS:Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS:Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION:This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols

Dementia Caregiver Burden: A Research Update and Critical Analysis

Purpose of Review: This article provides an updated review of the determinants of caregiver burden and depression, with a focus on care demands and especially the differential effects of various neuropsychiatric symptoms or symptom clusters. Moreover, studies on caregivers for frontotemporal and Lewy body dementias were referred to in order to identify differences and similarities with the mainstream literature based largely on Alzheimer caregivers. Recent Findings: As a group, neuropsychiatric symptoms are most predictive of caregiver burden and depression regardless of dementia diagnosis, but the effects appear to be driven primarily by disruptive behaviors (e.g., agitation, aggression, disinhibition), followed by delusions and mood disturbance. Disruptive behaviors are more disturbing partly because of the adverse impact on the emotional connection between the caregiver and the care-recipient and partly because they exacerbate difficulties in other domains (e.g., caring for activities of daily living). In behavioral variant frontotemporal dementia, not only are these disruptive behaviors more prominent but they are also more disturbing due to the care-recipient’s insensitivity to others’ feelings. In Lewy body dementia, visual hallucinations also appear to be distressing. Summary: The disturbing nature of disruptive behaviors cuts across dementia conditions, but the roles played by symptoms that are unique or particularly serious in a certain condition need to be explored further

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain

Background Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. Methods A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). Results High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29–0.87) and dependence (OR = 0.33; 95% CI = 0.19–0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22–0.70 and OR = 0.39; 95%CI = 0.21–0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. Conclusions Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.This project was partially funded by a research contract in support of the project “Epidemiological Study of Dementia in Spain” signed by the Pfizer Foundation and Carlos III Institute of HealthS

Prevalence of disability in a composite ≥75 year-old population in Spain: A screening survey based on the International Classification of Functioning

<p>Abstract</p> <p>Background</p> <p>The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF.</p> <p>Methods</p> <p>Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2^ndedition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100).</p> <p>Results</p> <p>The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32).</p> <p>Conclusions</p> <p>Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.</p