Adult Life Course Research Articles

Age dependent association between remnant cholesterol and cardiovascular disease

Background and aimsHigh remnant cholesterol is associated with cardiovascular disease (CVD), but whether CVD risk attributable to remnant cholesterol vary between young and later adults remains unknown. The study aimed to assess age differences in the association between remnant cholesterol and CVD. MethodsThis prospective study included 95 663 participants without CVD and lipid-lowering treatment at baseline, including 16 254 young adults (age 18–39 years) and 79 409 later adults (age ≥40 years). Individuals were grouped by clinically meaningful remnant cholesterol concentrations of <0.50, 0.50–0.99, 1.00–1.49, and ≥1.50 mmol/L. Multivariable Cox regressions were performed to calculate hazard ratio (HR). ResultsDuring a median follow-up of 11.01 years, 164 incident CVD were identified in young adults, and 6081 cases in later adults. After multivariate adjustment, the association between remnant cholesterol and CVD was more pronounced in young adults than later adults (P for interaction=0.0019), the HR was 2.24 (95% confidence interval [CI], 1.45–3.47) for young individuals with remnant cholesterol ≥1.50 mmol/L, compared to individuals with remnant cholesterol <0.50 mmol/L, while the corresponding HR was 1.21 (95% CI, 1.13–1.29) for later adults. Furthermore, the population attributable risk percentage for remnant cholesterol < 1.50 vs ≥ 1.50 mmol/L was also higher in young (14.8%) than later adults (4.2%). ConclusionsDespite a lower incidence risk of CVD among young adults compared later adults, the stronger association and greater attributable risk of remnant cholesterol among young adults highlight the importance of preventive efforts across the adult life course.

Moderate-to-vigorous intensity physical activity from young adulthood to middle age and metabolic disease: a 30-year population-based cohort study

ObjectivesTo determine the association between moderate-to-vigorous intensity physical activity (MVPA) trajectories (course over age and time) through the adult life course and onset of metabolic disease (diabetes and dyslipidaemia).MethodsWe analysed...

The “Sandwich Generation” Revisited: Global Demographic Drivers of Care Time Demands

AbstractGenerational overlap affects the care time demands on parents and grandparents worldwide. Here, we present the first global estimates of the experience of simultaneously having frail older parents and young children (“sandwichness”) or young grandchildren (“grandsandwichness”) for the 1970–2040 cohorts, using demographic methods and microsimulations. We find that sandwichness is more prevalent in the Global South—for example, almost twice as prevalent in sub‐Saharan Africa as it is in Europe for the 1970 cohort—but is expected to decline globally by one‐third between 1970 and 2040. The Global North might have reached a peak in the simultaneous care time demands from multiple generations but the duration of the grandsandwich state will increase by up to one year in Africa and Asia. This increasing generational overlap implies more care time demands over the entire adult life course, but also opens up an opportunity for the full potential of grandparenthood to materialize.

Twenty-Year Trajectory-Patterns of Percentage Energy From Dietary Fat vs. Carbohydrate Throughout Adult Life and Associations With Cardio-Metabolic Disease and All-Cause Mortality.

Background: The health impacts of dietary fat-to-energy ratio (FER) compared to carbohydrate-to-energy ratio (CER) are widely discussed topics in public health. This study aimed to assess the health impacts of FER and CER by establishing trajectory-patterns of FER and CER over the course of adult life.Methods: This study used the weighted longitudinal data of the China Health and Nutrition Survey, including eight surveys from 1991 to 2011. The trajectories of FER and CER were determined via latent class trajectory modeling. The trajectories were then cross-grouped into different trajectory-patterns. Multivariate Cox regression models were used to assess the relationship between these trajectory-patterns and cardio-metabolic diseases and all-cause mortality. Ten thousand nine hundred and twenty-six adults with a total of 50,693 observations across eight surveys were included.Results: Compared to the trajectory-pattern of persistently low-FER (increased from 10 to 20%) and moderate-CER (stable and ranging from 55 to 65%) over the adult life-course, the two trajectory-patterns that showed changing to high-FER and low-CER were significantly associated with obesity [HR 1.83 [95% CI, 1.10–3.04]; HR 1.46 [95% CI, 1.02–2.17]], diabetes [HR 1.80 [95% CI, 1.03–3.16]; HR 1.49 [95% CI, 1.01–2.25]], and all-cause mortality [HR 2.29 [95% CI, 1.35–3.87]; HR 1.62 [95% CI, 1.18–2.22]]. In contrast, the trajectory-pattern of a persistently low-FER and high-CER diet was not associated with obesity [HR 1.19 [95% CI, 0.82–1.17]], diabetes [HR 1.41 [95% CI, 0.98–2.02]], cardiovascular-disease [HR 1.48 [95% CI, 0.91–2.39]], and all-cause mortality [HR 1.23 [95% CI, 0.94–1.61]].Conclusions: This study indicates that changing to a high-FER and low-CER diet over the course of adult life was significantly associated with obesity, diabetes, and all-cause mortality in the Chinese adult population. In addition, low-FER and high-CER were not associated with cardio-metabolic disease and all-cause mortality. These observations may provide insights into nutritional policy and dietary guidelines.

The when and the how of the emergence of social inequality in mental health: Exploring social causation and health selection through employment transitions

How, and at what stage of the adult lifecourse, does the association between income and mental health problems arise? Research mostly tests whether mechanisms of social causation or health selection are evident in a given sample. I test for these mechanisms, and the contribution of unobserved heterogeneity, but additionally explore the extent to which each contributes to growth in social inequality in mental health, specifically symptoms of depression and anxiety and their negative correlation with household income. Using Understanding Society data, I first show that inequality in mental health among adults emerges around ages 20–30 and then persists, only weakening from around 60. Inequality is much lower controlling for employment. Next, I apply a novel fixed-effects longitudinal structural equation model to test three mechanisms generating growth of this inequality, operationalising social causation and health selection through employment transitions. While leaving employment exhibits a negative association with subsequent mental health, neither this mechanism nor the reverse – health selection out of employment – can account for growth in mental health inequality. Rather, only unobserved heterogeneity between individuals accounts for a substantial portion of this growth – around a third. This result is similar for men and women and across age groups. These findings lend support to the relatively neglected indirect health selection hypothesis, and indicate that a priority for future work should be to more clearly delineate what sorts of relatively fixed characteristics of individuals might matter, through what sorts of pathways, and how these characteristics are moulded across childhood and adolescence.

Abstract 853: Body mass index trajectories across the adult life course and pancreatic cancer risk

Abstract Background: Adiposity is associated with pancreatic ductal adenocarcinoma (PDAC), but the effects of weight excess over an adult life course have not been studied extensively. We examined the association between trajectories of body mass index (BMI) from ages 18 up to 71 years and risk of subsequent PDAC. Methods: Our analysis included 270,722 (163,873 men, 106,849 women) NIH-AARP Diet and Health Study participants, 50-71y, who successfully completed questionnaires with self-reported height and weight at ages 18, 35, 50 and at baseline (50-71y, 1995-1996) and from which BMI (kg/m2) was calculated. We used latent class growth mixture modeling to identify BMI trajectories using adult BMI reported at each of the four timepoints. We identified BMI trajectories for all sample combined and separately for men and women. We then examined the association between BMI trajectories and incident PDAC using Cox proportional hazards models to calculate age, smoking, and sex adjusted hazard ratios (HR) and 95% confidence intervals (CI) overall and by sex. Participants that maintained normal weight status over their adulthood were set as the referent group. Results: Over an average follow-up time of 13.1 years (max: 15.17 years), 3105 incident PDAC cases (2033 men, 1072 women) were identified in the overall cohort. We identified four overall and sex specific BMI trajectory groups, each with one maintainer and three increasers. Participants either maintained normal weight (N-N, 37.1% of the cohort), or increased from normal-overweight (N-OW, 36.4%), normal-obese (N-O, 20.7%), or normal-severely obese (N-SO, 5.8%). The male cohort was divided into N-N (35.5%), N-OW (23.3%), normal-higher overweight (N-HOW, 34.8%), and N-SO (6.6%) while the female cohort was divided into N-N (51.6%), N-OW (34.5%), N-SO (11.3%), and OW-SO (2.7%). Compared to N-N, the N-OW (HR=1.12, 95% CI 1.03-1.21), N-O (1.22, 1.11-1.35) and N-SO (1.22, 1.04-1.45) groups were at significantly increased risk for PDAC. Compared to the sex-specific maintainer groups, men in the N-OW (1.14, 1.02-1.28), N-HOW (1.16, 1.04-1.29), and N-SO (1.39, 1.15-1.67) groups were significantly associated with PDAC, while only women in the N-OW (1.12, 1.00-1.29) group showed a borderline significant association. Adding diabetes to the models slightly attenuated the associations by less than 10% with the greatest attenuation observed in the SO groups. The overall associations were not significantly modified by sex (P-interaction = 0.10) or smoking status (never, former, current, P-interaction = 0.17). Conclusions: In this large prospective cohort study, increasing BMI throughout adulthood was associated with a greater risk for PDAC. Citation Format: Simran Arjani, Pedro F. Saint-Maurice, Sachelly Julian-Serrano, Rachael Stolzenberg-Solomon. Body mass index trajectories across the adult life course and pancreatic cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 853.

Musical instrument engagement across the life course and episodic memory in late life: An analysis of 60 years of longitudinal data from the Wisconsin Longitudinal Study.

BackgroundAs the global burden of dementia increases, the absence of treatment underscores the need for identification of factors that may improve cognitive reserve–the ability to stave off cognitive decline in old age. The beneficial association between musical instrument engagement and episodic memory has been identified in children, young adults, and older adults. Yet, previous studies in musical instrument engagement have rarely examined the potential for adolescence and adulthood exposures to independently improve cognition, nor have they been linked with the rate of memory decline over time in older adults. We investigated whether adolescent musical instrument engagement and continued musical instrument engagement over the adult life course were separately associated with higher episodic memory, as well as rate of decline in a large longitudinal cohort.MethodsData were from a prospective cohort of high school graduates from 1957. High school music engagement (HSME) was ascertained through graduate yearbooks and assessed as membership in musical performance groups. A questionnaire was used to assess musical engagement through adulthood (MEA) at ages 35, 55, and 65. The episodic memory score was composed of immediate and delayed recall task scores, and was assessed when participants were aged approximately 65 and 72 years old among 5,718 individuals. Linear mixed models were used to assess the association between music, and memory performance and decline over time.ResultsOf high school graduates who participated in the study, 38.1% played music in high school, and 21.1% played music in adulthood. While musical engagement was more common in those who played in childhood, 40% of those who played continuously as an adult did not play in high school. High HSME (B = 0.348, p = 0.049) and continuous MEA (B = 0.424, p = 0.012) were associated with higher memory scores at age 65 after covariate adjustment. When examining memory decline, the benefits of high HSME decreased over time (B = -0.435, p = 0.048), while the rate of decline did not differ between MEA groups. Exploratory models revealed differential benefits for HSME and immediate recall, and MEA and delayed recall.ConclusionThis study provides further evidence that musical engagement in childhood or adulthood is associated with non-musical cognitive reserve. These two exposures may act differentially in different domains of episodic memory. Further work is needed to determine the relationship between musicianship and the rate of cognitive decline.

Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells.

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the 'sterile' activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.

Physical Activity and Hypertension From Young Adulthood to Middle Age

The optimum physical activity dose to achieve during young adulthood to prevent hypertension using the 2017 American College of Cardiology/American Heart Association guidelines remains undefined. This study aims to determine the association between level and change in physical activity through the adult life course and the onset of hypertension using these 2017 definitions. In 2020, prospective community-based cohort data of 5,115 Coronary Artery Risk Development in Young Adults study participants were analyzed. The cohort included Black and White men and women aged 18-30 years at baseline (1985-1986) at 4 urban sites, collected through 30 years of follow-up (2015-2016). Individualized physical activity trajectories were developed for each participant using linear mixed models. Black women reported the lowest physical activity levels from young adulthood through middle age. Lower physical activity score (per 100 units) at age 18 years was associated with 4% (95% CI=1%, 7%, p=0.002) higher odds of hypertension incidence. Each additional 1-unit reduction per year in physical activity score was associated with 2% (95% CI=1%, 3%, p=0.001) higher annual odds of hypertension incidence. Meeting approximately the current minimum physical activity guideline levels at age 18 years and through follow-up was not protective of hypertension incidence; however, meeting approximately twice the current minimum physical activity guideline level at age 18 years and through follow-up was protective of hypertension incidence. Moderate physical activity levels may need to exceed current minimum guidelines to prevent hypertension onset using 2017 American College of Cardiology/American Heart Association definitions.

Enhancing Literacy and Communicative Skills of Students With Disabilities in Special Schools Through Dialogic Literary Gatherings.

Enhancing the quality of learning opportunities for students with disabilities and the learning level attained is a pending challenge. This challenge is especially relevant in the context of special schools, where the learning possibilities derived from interactions with others is limited. However, providing these students with a sufficient level of instrumental learning, such as literacy, and communicative and reasoning abilities is crucial for their subsequent educational and social opportunities. In this case study we analyse a special school that has implemented Dialogic Literary Gatherings with their students as a means to increase learning interactions within the group around the reading and debate of classical books. Semi-structured interviews were conducted with the school principal and with a teacher of the transition to adult life course, and two focus groups were conducted with teachers–one with primary education teachers and one with secondary education teachers–and two focus groups with students–one with primary education students and one secondary education and transition to adult life students–. On the one hand, results show the characteristics of the Dialogic Literary Gatherings that allowed these students to participate and learn. On the other hand, several improvements have been observed. First, regarding instrumental learning, students increased their motivation for reading, and improved their communicative and reasoning abilities and in their reading proficiency. Second, regarding students' behavior, conflict has reduced, solidarity attitudes have increased, and they have acquired dialogic and argumentative habits. Finally, at the emotional level, they gained self-esteem and confidence and feel more empowered to make their voice heard.

Changes in BMI from young adulthood to late midlife in 1536 Danish men: The influence of intelligence and education

Intelligence and education have both been associated with body mass index. However, few longitudinal studies have simultaneously investigated the importance of intelligence and education for changes in body mass index (BMI) over time. This longitudinal study included 1536 Danish men with information about intelligence, educational level and BMI in young adulthood and BMI 41 years later in late midlife. Mean BMI increase was 5.1 kg/m 2 . Higher intelligence in young adulthood was significantly associated with less gain in BMI. The association attenuated when adjusting for level of education. Higher education was associated with less gain in BMI and these associations remained significant when adjusting for intelligence. The findings suggest that both intelligence and educational level in young adulthood are associated with changes in BMI from young adulthood to late midlife with education being the stronger predictor of BMI changes across the adult life course. • Young adult intelligence and education are associated with changes in BMI from age 18 to age 61. • Education is a stronger predictor of BMI changes across the adult life course than intelligence. • High educational level was associated with less increase in BMI across the adult life course. • Non-cognitive factors related to education may be important for BMI changes during adulthood.

Intelligence, health and death.

The field of cognitive epidemiology studies the prospective associations between cognitive abilities and health outcomes. We review research in this field over the past decade and describe how our understanding of the association between intelligence and all-cause mortality has consolidated with the appearance of new, population-scale data. To try to understand the association better, we discuss how intelligence relates to specific causes of death, diseases/diagnoses and biomarkers of health through the adult life course. We examine the extent to which mortality and health associations with intelligence might be attributable to people's differences in education, other indicators of socioeconomic status, health literacy and adult environments and behaviours. Finally, we discuss whether genetic data provide new tools to understand parts of the intelligence-health associations. Social epidemiologists, differential psychologists and behavioural and statistical geneticists, among others, contribute to cognitive epidemiology; advances will occur by building on a common cross-disciplinary knowledge base.

Male childlessness across the adult life course: A case study addressing a potentially 'vulnerable' population.

Like other Latin American countries, over the past half-century, Colombia has experienced rapid urbanization, dramatic fertility decline, and massive educational expansion. These socio-demographic changes have transformed gender roles and, with them, the landscape surrounding reproductive decisions, family life, and opportunities in other life 'domains.' I draw on the 'life course cube' (LCC) approach, which frames individual actions within a multidimensional behavioral process shaped by interdependencies between time, life domains, and levels to explore Colombian male childlessness. I seek to answer two questions: How does Colombian non-fatherhood vary across the life course (with respect to overall prevalence and associated factors)? and How do men frame their non-fatherhood, and, especially, how do they envision a future without children? To address the first question, I used the 2015 Colombian Demographic and Health Survey's men's dataset (N > 30,000) to explore the overall level of male childlessness across age/generational groups and separate voluntary/involuntary childlessness. Then, using generalized linear models, I analyzed the relationships between different life domains (e.g. education, employment) and non-fatherhood at time points representing early-, mid-, and later-life childlessness (among men in their thirties, forties, and fifties). To address the second question, I used qualitative data from in-depth life history interviews I conducted with male (N = 7) and female (N = 28) parents/non-parents in Bogotá, analyzing connections between different 'levels' of men's experiences: their inner feelings, past and (envisioned) future actions, and societal factors framing childlessness. The quantitative findings indicate that male childlessness across the adult life course is strongly associated with later start of first union/never entering a union, and with small ideal family size. Later-life, definitive childlessness is also strongly associated with relative economic disadvantage and lower-prestige occupations, though early-life fatherhood postponement is not. Qualitatively, interviewed men expressed more worry and less preparation for the future than childless women. Understanding 'vulnerability' as 'the dynamics of stress and resources across the life course', I discuss these findings, paying attention to older non-fathers' potential psycho-social, relational, and socioeconomic vulnerability. Therefore, this work seeks to contribute to the literature on the determinants and experiences of male childlessness, focusing on a Latin American perspective.

Age dependent associations of risk factors with heart failure: pooled population based cohort study

ObjectiveTo assess age differences in risk factors for incident heart failure in the general population.DesignPooled population based cohort study.SettingFramingham Heart Study, Prevention of Renal and Vascular End-stage Disease Study, and...

Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study.

Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from 4 prospective cohorts (n = 15,001, ages 18-95). We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, midlife, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Examination [3MS]) and processing speed (Digit Symbol Substitution Test [DSST]), adjusting for demographics, education, and cohort. Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late life (<80 years) but with gains in very late life (≥80 years). After adjusting for CVRF exposures at all time periods, the associations for early adult and late-life CVRFs persisted. We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late life may not be as helpful for these outcomes.

The age pattern of the male-to-female ratio in mortality from COVID-19 mirrors that of cardiovascular disease in the general population.

Males are at a higher risk of dying from COVID-19 than females. Older age and cardiovascular disease are also associated with COVID-19 mortality. To better understand how age and sex interact in contributing to COVID-19 mortality, we stratified the male-to-female (sex) ratios in mortality by age group. We then compared the age-stratified sex ratios with those of cardiovascular mortality and cancer mortality in the general population. Data were obtained from official government sources in the US and five European countries: Italy, Spain, France, Germany, and the Netherlands. The sex ratio of deaths from COVID-19 exceeded one throughout adult life, increasing up to a peak in midlife, and declining markedly in later life. This pattern was also observed for the sex ratio of deaths from cardiovascular disease, but not cancer, in the general populations of the US and European countries. Therefore, the sex ratios of deaths from COVID-19 and from cardiovascular disease share similar patterns across the adult life course. The underlying mechanisms are poorly understood and warrant further investigation.

42. Physical Activity From Young Adulthood to Middle Age and Cardiovascular Disease Risk Factors: The Coronary Artery Disease in Young Adults Study

Few studies have examined the association of physical activity from young adulthood to middle age with later-adult cardiovascular disease risk factors (hypertension, diabetes, and dyslipidemias) due to limitations in the availability of longitudinal cohort data spanning these periods. The purpose of this study was to determine the association between physical activity trajectories (level and change) throughout the adult life course and incidence of cardiovascular disease risk factors (hypertension, diabetes, and dyslipidemias).

The association of APOE \u03b54 with cognitive function over the adult life course and incidence of dementia: 20\u2009years follow-up of the Whitehall II study

BackgroundApproximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer’s disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age.MethodsA cohort study of 5561 participants (mean age 55.5 (SD = 5.9) years, 27.1% women) with APOE genotyping and repeated cognitive tests for reasoning, memory, and semantic and phonemic fluency, during a mean (SD) follow-up of 20.2 (2.8) years (the Whitehall II study). We used joint models to examine the association of APOE genotype with cognitive function trajectories between 45 and 85 years taking drop-out, dementia, and death into account and Fine and Gray models to examine associations with dementia.ResultsCompared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%) APOE ε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45–85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function.ConclusionsBoth heterozygous and homozygous ε4 carriers had poorer cognition and greater risk of dementia at older ages. Our findings show some support for a complex antagonist pleiotropic effect of APOE ε4 heterozygosity over the adult life course, characterized by cognitive advantage in midlife.

Межрегиональная миграция молодежи в России и выстраивание жизненных стратегий

There is lack of studies associating youth migration with a life course in Russia. The article aims to reveal the effect of interregional migration on the life course of young adults (23–34 y.o.) using the data from the nationally representative survey “Person, Family, Society” undertaken by RANEPA in 2020 and data from indepth interviews with young people who moved to Moscow, St. Petersburg, Tomsk, Voronezh to get higher education. In the study interregional migrants are defined as people for whom current region of residence differs from the region where they completed secondary education. Our results suggest that migration is a strong factor of personal growth for youth. The comparison of young migrants with non-migrants demonstrates that the interregional migration have a distinct positive effect on career success, income level and promote greater independence and relying on your own resources, solving housing issues among them. The comparison of young migrants and non-migrants demonstrates that the interregional migration has a distinct positive effect on career success, income level and promote greater independence and selfreliance including resolving the housing problems. At the same time migration moderately affects marriage strategies but it contributes to the postponement of childbearing.

Housing and Environmental Uncertainty in Constructions of Exclusion Arising From Critical Life-Course Ruptures

There is growing recognition that the older adult life course can involve critical transitions that function as significant sources of adversity, and ruptures in life trajectories. While knowledge about how these ruptures generate multidimensional disadvantage remains underdeveloped, less is known about how they are spatially constituted and how their processes and outcomes may be mediated by older peoples’ relationship with place. Utilizing a ‘sense of home’ as a conceptual orientation, this paper explores the role of place in social exclusion arising from life-course ruptures. Focusing on bereavement, dementia on-set and forced migration, it draws data from 45 life-course interviews. Place (e.g. home environment and the wider community) was involved in three ways: as a component of the rupture; as a life domain where people experience exclusion; and as a mediator of exclusionary processes. Circularity is observed, with perceived environmental uncertainty intensifying effects of rupture-related exclusion, further contributing to that uncertainty.