Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011–2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors—cognitive and social activity, physical activity, diet, alcohol consumption, and smoking—and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%–23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%–27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life.

Background Social exclusion of the elderly is a key policy focus but evidence on the processes linking health and social exclusion is hampered by the variety of ways that health is used in social exclusion research. We investigated longitudinal associations between health and social exclusion using an analytical framework that did not conflate them. Methods Data employed in this study came from 4 waves of Understanding Society, the UK Household Longitudinal Study 2009–2013. The sample comprised all adults who took part in all 4 waves, were 65 years or more in Wave 3, and had complete data on our variables of interest for each analysis. We used linear regression to model the relationship between Wave 2/3 social exclusion and Wave1–2 health transitions (N=4312) and logistic regression to model the relationship between Wave2/3 social exclusion and Wave 4 health states, conditional on Wave 3 health (N=4244). Results There was a dose–response relationship between poor health in Waves 1 and 2 and later social exclusion. Use of a car, mobile phone and the internet moderated the association between poor health and social exclusion. Given the health status in Wave 3, those who were more socially excluded had poorer outcomes on each of the three domains of health in Wave 4. Conclusions Use of the internet and technology protected older adults in poor health from social exclusion. Age-friendly hardware and software design might have public health benefits.

Social exclusion is a dynamic multi-dimensional process that is interactive in nature. The complex interplay between domains, whereby each domain can act as a determinant, indicator and/or outcome of social exclusion, hinders understanding of the process and the mechanisms through which social exclusion exists. This article highlights the need to disentangle these pathways and move beyond descriptive accounts of social exclusion, presenting a new working framework that allows direct hypothesis testing of these between-domain relationships. Whilst this working framework can be applied to any population, this article focuses on older adults. Life events that can drive social exclusion such as bereavement and changes in health are more likely to occur in later life, and occur more frequently, increasing the risk of social exclusion for this population. Rooted in the new working framework, this article presents the construction of later life social exclusion measures for use with Understanding Society – the United Kingdom Household Longitudinal Study. The validity of these measures are considered by examining the characteristics of those aged 65 years and over who score the highest, and therefore experience the greatest level of exclusion. This new working framework and developed social exclusion measures provide a platform from which to explore the complex relationships between domains of social exclusion and ultimately provide a clearer understanding of this intricate multi-dimensional process.

Background: Co-morbidity is a major late-life challenge with poor outcomes, yet many older people are resilient. We consider an ecopsychosocial framework of resilience to investigate this disparity. This theorises that sources of resilience may be personal, social and structural. We explored older people's responses and reactions to significant life experiences, to understand resilience development for managing later life health challenges. Methods: We applied a two-stage, cross-sectional mixed-methods design to the Cognitive Function and Ageing Studies Wales (CFAS Wales). Participants' defined quantitatively as resilient (high level of well-being despite co-morbidity) were identified in the wave 1 dataset. A sub-sample of the resilient participants aged 65+ were randomly selected for semi-structured interviews (N = 20). Qualitative thematic analyses were both inductive and deductive. Results: The analyses revealed four primary life experiences reflecting different developmental trajectories. “Early years as formative” and “work and employment as formative” occurred at normative developmental stages in the life-course. In contrast non-normative life events such as loss, bereavement, illness of self, and others underpinned the themes of “adverse events and experiences” and “caring experiences.” Four potential mechanisms for resilience were central to these life experiences, reflecting reactions, actions, and development: “character and self-identity;” “approach to life and insight;” “meaningful relationships and belonging.” Conclusions: This work contributes further theoretical insights into the ecopsychosocial resilience framework. It highlights the process of interdependence between the individual and the wider environment, suggesting how the availability and accessibility of resources and human agency (protective factors), can influence, and be influenced by, the timing of significant events and experiences. In doing so, it corroborates international healthy ageing policy which recognises resilience as important for a public health response to support older people to adjust to changes and losses experienced in later life. It highlights the importance of current and future policies and services for supporting the management of adverse events earlier in the life-course, and recommends that policies and services take a “long view” on population health and well-being and consider the whole life-course, in addition to specific points in the ageing process.

Legislation places an onus on local authorities to be aware of care needs in their locality and to prevent and reduce care and support needs. The existing literature overlooks ostensibly ‘healthy’ and/or non-users of specific services, non-health services and informal assistance and therefore inadequately explains what happens before or instead of individuals seeking services. We sought to address these gaps by exploring older adults’ accounts of seeking assistance in later life. we conducted semi-structured qualitative interviews with 40 adults aged 68–95. We invited participants to discuss any type of support, intervention, or service provision, whether medical, social, family-provided, paid or unpaid. this paper reports older people’s accounts of how they evaluated their need for assistance. We found that the people in our sample engaged in a recursive process, evaluating their needs on an issue-by-issue basis. Participants’ progression through this process hinged on four factors: their acknowledgement of decline; the perceived impact of decline on their usual activities and independence; their preparedness to be a recipient of assistance; and, the opportunity to assert their need. In lieu of seeking assistance, participants engaged in self-management, but also received unsolicited or emergency assistance. older people’s adaptations to change and attempts to meet their needs without assistance mean that they do not present to services, limiting the local authority’s knowledge of their needs and ability to plan appropriate services. Our findings offer four stages for policymakers, service providers and carers to target to address the uptake of assistance.