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.

The COVID-19 global pandemic and subsequent public health social measures have challenged our social and economic life, with increasing concerns around potentially rising levels of social isolation and loneliness. This paper is based on cross-sectional online survey data (available in 10 languages, from 2 June to 16 November 2020) with 20,398 respondents from 101 different countries. It aims to help increase our understanding of the global risk factors that are associated with social isolation and loneliness, irrespective of culture or country, to support evidence-based policy, services and public health interventions. We found the prevalence of severe loneliness was 21% during COVID-19 with 6% retrospectively reporting severe loneliness prior to the pandemic. A fifth were defined as isolated based on their usual connections, with 13% reporting a substantial increase in isolation during COVID-19. Personal finances and mental health were overarching and consistently cross-cutting predictors of loneliness and social isolation, both before and during the pandemic. With the likelihood of future waves of COVID-19 and related restrictions, it must be a public health priority to address the root causes of loneliness and social isolation and, in particular, address the needs of specific groups such as carers or those living alone.

The Bangor Longitudinal Study of Ageing (BLSA), conducted in rural Wales from 1979 to 1999, followed a cohort of survivors from more than 500 people over 20 years. Using both quantitative and qualitative data from the study, the factors associated with increases and decreases in loneliness and social isolation were identified. The study was based on a population sample and survivors were followed up every 4 years. From 1983 to 1987, 30 people aged 75 and over in 1979 were studied intensively. The customary measure of loneliness was used, as well as an aggregate measure devised by the research team. Social isolation was similarly measured, using an aggregate measure. Respondents were assessed as demonstrating low, moderate, or high levels of loneliness or isolation. Subsequently, statistical models of loneliness and social isolation were developed. Some respondents were assessed as not experiencing social isolation or loneliness during the study. Others showed changes in levels. In this article, the data are explored, seeking factors associated with changes in social isolation and loneliness. Outcome measures of these two variables of interest are compared with items from the aggregate measures and other identifiable intervening variables. The article discusses which change variables contribute most to levels of isolation and loneliness and result in different combinations of these two outcomes. Implications for policy and practice are discussed.

Background The Short Form 36 Health Survey Questionnaire (SF-36) is used to indicate the health status of particular populations, to help with service planning and to measure the impact of clinical and social interventions. Culture-specific data are required to calculate SF-36 norm-based scores. Currently, in the UK normative sources are nearly two decades old, Anglocentric and lack data on the older population. We draw on raw data from the Welsh Health Survey (2007) to provide population norms for the eight SF-36 dimensions for Wales and its regions. Methods We test the SF-36 dimensions for reliability and rating scaling assumptions and construct validity. We compare the Wales’ norms to those reported in existing UK sources and examine the data between countries and by region. Results The scale is reliable and has content validity. The relationships found between the SF-36 domains and a range of variables known to be related to health also demonstrate construct validity. There are differences in population health norms between England and Wales and between the regions of Wales. Conclusions The results suggest that it is imperative that the accurate normative data provided in this paper is used in population studies in Wales to provide an indication of the health status of particular populations.

We draw on cognitive discrepancy theory to hypothesize and test a pathway from poor health to loneliness in later life. We hypothesize that poor health will have a negative influence on social participation and social resources, and these factors will mediate between health and loneliness. We hypothesize that rural environments will amplify any difficulties associated with social participation or accessing social resources and that depression will moderate how intensely people react to levels of social contact and support. We conceptualize a mediation model and a moderated-mediation model. Nationally representative data on older people living in the Republic of Ireland are used to validate the hypothesized pathways. In the mediation model, health has a significant indirect effect on loneliness through the mediating variables social resources and social participation. In the moderated-mediation model, rurality moderates the pathway between health and social resources but not social participation. Depressive symptoms moderate the effect of social resources on loneliness but not social participation. The results provide further credence to cognitive discrepancy theory, suggesting that depressive symptoms influence cognitive processes, interfering with judgments about the adequacy of social interaction. The theory is extended by demonstrating the impact of the environment on loneliness.