Demographic Research

BackgroundLifespan inequality arises both from heterogeneity (e.g., in sex or race) and from unavoidable individual stochasticity. By treating a heterogeneous population as a mixture we can (and many have) partition variance in lifespan into a between-group component due to heterogeneity and a within-group component due to chance. Until now, such studies have treated factors singly. It is now possible to analyze multiple factors and their contributions to variance. ObjectiveThis paper is the first to exploit the new analysis for multi-factor studies. Multi-factor data are painfully rare, but a remarkable study by Bergeron-Boucher et al. presented U.S. life tables under all 54 combinations of four factors (sex, marital status, education, race). Our objective is to quantify the contributions of these factors and their interactions to lifespan inequality. MethodsThe population is treated as a mixture of 54 groups, with a mixture distribution either flat or proportional to population size of the different factor combinations. Components of the variance in remaining longevity, for starting ages from 30 to 85 years, are calculated using marginal mixture distributions. ResultsEven accounting for four factors and their interactions, between-group heterogeneity accounts for only 7% (population-weighted mixing) to 10% (flat mixing) of lifespan variance. Education and its interactions make the largest contribution. Contributions of two-way, three-way, and four-way interactions are orders of magnitude smaller. This suggests new ways of displaying, summarizing, and interpreting inequality as measured in multi-factor studies. ContributionMulti-factor studies can now be used to identify sources of variance in longevity and other demographic outcomes.

Population ageing increases the importance of cognitive capacity for making decisions about retirement and living independently beyond it. We tested whether post-war educational expansion and working-life social mobility eliminate the association between social class of origin and cognition in early old age using the 1958 National Child Development Study. Two outcomes were analysed at age 62: standard episodic memory (immediate + delayed word recall) and long-term episodic memory, capturing accurate half-century recall of childhood household facts (rooms and people at age 11 validated against mothers' responses). Social mobility trajectories derived in prior work were classified into predominantly manual versus non-manual class trajectories. Models were estimated separately for women and men across three specifications: (i) social origin and controls, (ii) adding social mobility, and (iii) adding weighting to address healthy survivor bias. Education was consistently associated with both outcomes. For long-term episodic memory, social origin gradients were clearer than for short-term episodic memory, with men from service/professional origins showing a 13 percentage-point higher probability of accurate half-century recall than men from manual origins. These findings indicate that education expansion and working-life social mobility failed to release the grip of social origin on long-term episodic memory.

Period Life Expectancy (PLE) is a measure of longevity valued for its sensitivity to short and long-term changes. However, it refers to a hypothetical cohort, not to a real population, thereby undervaluing longevity under declining mortality conditions. Other measures such as the Average Cohort Life Expectancy (ACLE) only partially overcome this limitation, still underestimating population longevity. This article introduces a new indicator, the Population Life Expectancy (PoLE), defined as the mean age at death of active cohorts in the studied population. Using a log-linear Poisson model with age-period interaction to project mortality of non-extinct cohorts, we estimated PoLE in Switzerland and Norway over 1876-2024, and compared it to PLE, Cohort Life Expectancy (CLE), and ACLE. PoLE clearly exceeded PLE, increasing from 63.3 to 89.7 for Swiss men (PLE from 37.7 to 82.4), and from 65.4 to 91.3 for Swiss women (PLE from 41.4 to 85.9), revealing a gain of about +50% over 150 years, rather than +100% suggested by PLE. Comparable results were obtained in Norway. PoLE was also higher than CLE until the mid-20th century, when the relation reversed, indicating that life expectancy is now higher for newborns than for those already alive, a tangible sign of human progress.

ObjectivesGrowth Mindset and Grit have been proposed as key psychological resources for resilience and adaptation, yet their manifestation and social distribution in later life remain underexplored. This study examines the structure, distribution, and correlates of Growth Mindset and Grit in older adulthood using proxy indicators in the English Longitudinal Study of Ageing (ELSA). MethodsProxy indicators reflecting learning behaviour, personality traits, affect, and beliefs were used to derive three components of Growth Mindset (education-, personality-, and belief-based) and two components of Grit (affective- and personality-based). Multinomial logistic regression models examined associations with age, socioeconomic position, health, and cognitive functioning. ResultsDistinct distributional patterns emerged across components. Education-based Growth Mindset was concentrated in lower categories, whereas personality-, belief-, and affect-based components showed greater variability. Older age was associated with lower Growth Mindset, particularly in education- and belief-based domains, while associations with Grit were more nuanced, including a lower likelihood of low affect-based Grit among older adults. Higher educational attainment, employment, wealth, and better memory performance were associated with more favourable profiles across selected domains. Living alone and limiting longstanding illness were consistently associated with less favourable profiles. ConclusionsGrowth Mindset and Grit appear to function as multidimensional and socially patterned psychological resources in later life. Belief-, personality-, and affect-based components capture meaningful variation even when formal learning declines, underscoring the importance of distinguishing opportunity-constrained indicators from dispositional domains in ageing research.

Recent progress in mathematical kinship modelling has allowed one to predict the probable numbers of kin for a typical population member. In the models, kin may be structured by age and sex, both in static or time-variant demographies. Knowing the probable numbers of kin in different stages - such as parity, health status, or geographic location - however, remains an open challenge in Kinship Demography. Knowing how population structure delimits kin to distinct stages is an advance - for instance, the probability of having one sister at home and one sister away has different social implications from the probability of having two sisters. We present a novel analytical framework, grounded in branching process theory, that provides kin-number distributions jointly structured by age and stage. Using recursive compositions of probability generating functions (PGFs), we derive the joint age, stage, and age x stage kin-number distributions. All marginal distributions over either dimension naturally emerge. Simple extensions of the PGF approach additionally yield: the joint distribution of an individuals own stage and their kins stage; the probable numbers of kin deaths, both in total and by generation number; and the probabilities of being kinless and/or orphaned. We demonstrate the framework through novel results in an application using UK parity-specific fertility and mortality data. HighlightsO_LIA new method calculates probability generating functions for the number of kin structured by age and stage C_LIO_LIThe model allows predicting the probable numbers of kin organised by age and stage C_LIO_LIRecursive nesting of probability generating functions in branching processes is used C_LIO_LIAn application is presented highlighting the novel results C_LI

This study investigated retirement adjustment in retired police officers in the UK (N = 289), examining how time since leaving the service moderates the relationship between perceived organisational support and retirement adjustment while accounting for resilience. Results indicated a developmental trend: organisational support remains stable initially but becomes increasingly influential in later life. Using Johnson-Neyman analysis, a threshold of 32.07 years was identified, after which the association reaches statistical significance. These findings suggest an organisational legacy effect; for the older generation, the retrospective perception of being valued by the service acts as a durable psychological resource. This study offers a novel conceptualisation of long-term organisational influence by identifying a temporally delayed legacy effect that extends beyond existing models of retirement adjustment. The study advocate for lifelong wellbeing strategies that extend, recognising that the organisational relationship continues to shape adjustment outcomes decades after the conclusion of active duty.

The basic reproduction number of an infectious disease is known to depend on the structure of contacts between individuals in a population. This relationship has been explored mathematically through two well-known models: one which depends on a matrix of contact rates between different demographic groups, and another which depends on the variability of contact rates over the population. Here we introduce a model that combines and generalises these two approaches. We derive a formula for the basic reproduction number and validate it through comparisons to simulated outbreaks. Applying this method to contact survey data collected in Belgium between 2020 and 2022, we find that our model produces higher estimates of the basic reproduction number and larger relative changes over periods when social contact behaviour was changing during the COVID-19 pandemic. Our analysis suggests some practical considerations when using contact data in models of infectious disease transmission.

Chronic pain has been identified as a risk factor for cognitive decline in later life. However, most studies measure pain at a single time point and none have investigated whether variations in pain severity are associated with changes in cognitive function over time. This project aimed to assess the relationship between individual-level change in pain severity and decline in cognitive function over time. We used data from the English Longitudinal Study of Ageing (ELSA), a cohort of nationally representative middle aged and older adults. Pain severity was measured at each wave using a 4-point scale (none, mild, moderate and severe) and cognitive function was assessed using 3 objective tests. We applied latent growth curve modelling, a method for longitudinal analysis, to 19,376 ELSA participants data collected over 11 waves, spanning more than 20 years, to examine the relationship between initial level and change of both pain and cognitive function. Adjusting for age and sex, worsening chronic pain severity was associated with accelerated decline in a general measure of cognitive function ({beta} = -0.053, p = 0.039). However, when additionally adjusting for ethnicity, socioeconomic status and comorbid chronic conditions, this association was attenuated to non-significance ({beta} = -0.025, p = 0.365). Greater initial pain severity was associated with steeper decline in cognitive function even in the fully adjusted model ({beta} = -0.104, p < 0.001). Our study suggests that baseline level of pain severity but not worsening pain severity is associated with steeper decline in cognitive function over time. SUMMARYAge- and sex-adjusted analyses find that higher baseline and worsening pain severity predict faster cognitive decline; only baseline pain remains significant after full adjustment.

Objectives: Longer lifespans lead to longer time on retirement, despite the efforts to raise the retirement age. Therefore, it is important to study how the retirement years can be spent without diseases. This study examined socioeconomic and sociodemographic differences in healthy years spent on retirement. Methods: We followed a cohort of retired Finnish municipal employees (N=4231, average follow-up 15.4 years) on national administrative registers for major chronic diseases: cancer, coronary heart disease, cerebrovascular disease, diabetes, asthma or chronic obstructive pulmonary disease, dementia, mental disorders, and alcohol-related disorders. Median healthy years on retirement and age at first occurrence of illness (ICD-10 and ATC-based) in each combination of sex, occupational class, and age of retirement were predicted using Royston-Parmar models. Prevalence rates for each diagnostic group were calculated. Results: Most healthy years on retirement were spent by women having worked in semi-professional jobs who retired at age 60-62 (median predicted healthy years 11.6, 95% CI 10.4-12.7). The least healthy years on retirement were spent by men having worked in routine non-manual jobs who retired after age 62 (median predicted healthy years 6.5, 95% CI 4.4-9.5). Diabetes was slightly more common among lower occupational class women, and dementia among manual working women having retired at age 60-62. Discussion: Healthy years on retirement are not enjoyed equally by women and men and those who retire early or later. Policies aiming to increase the retirement age should consider the effects of these gaps on retirees and the equitability of those effects.

Background Childhood socioeconomic position (SEP) is a key determinant of later life health. Understanding the extent to which adult SEP mediates this association into early old age is important for explaining how health inequalities are propagated across generations and how they might be addressed in later life. To our knowledge, no prospective study has examined whether childhood SEP remains associated with health at the threshold of older age and the extent to which any such association is mediated by adult SEP. Methods We used data from the 1958 British Birth Cohort, a prospective study that has followed participants since birth, drawing on earlier data collected at birth and ages 33 and 55 years and newly collected data from the age 62 sweep. Using interventional causal mediation analyses, we assessed whether adult occupational class, education, housing tenure, and income mediate associations between childhood social class (manual vs non manual) and health at age 62 (self rated health, C reactive protein [CRP], cholesterol ratio, Glycated hemoglobin [HbA1c], and N terminal pro B type natriuretic peptide [NT proBNP]). Findings Associations between childhood SEP and self rated health, CRP, cholesterol ratio, and HbA1c persisted after accounting for adult SEP. Mediation was outcome specific and differed by sex. Among men, occupational class mediated 39% of the association with self rated health (indirect effect RR 0.90, 95% CI 0.86,0.95) and education mediated 27% (0.93, 0.90,0.96). Among women, education mediated 10% (0.95, 0.91,0.98) and housing tenure mediated 6% (0.97, 0.94,0.99). Indirect effects for CRP were smaller, and mediation was minimal for cholesterol ratio, HbA1c, and NT proBNP Interpretation Population level improvements in adult SEP could reduce, but are unlikely to eliminate, later life health inequalities associated with childhood SEP. Reducing these inequalities will require policies that address disadvantage in early life and improve adult financial and employment conditions. Funding UK Economic and Social Research Council

BackgroundWith the rapid ageing of Irans population, accidents among institutionalised older adults represent a major public health concern. This study aimed to determine the prevalence, characteristics, and risk factors of accidents among elderly residents of nursing homes in Shiraz, Iran, during 2024, with particular emphasis on functional limitations. MethodsA cross-sectional census-based study was conducted in all seven nursing homes in Shiraz, involving 550 residents aged [&ge;]60 years. Data were collected through structured interviews, review of medical records, caregiver reports, and an Accident Form. Accidents occurring during the previous year were analyzed using descriptive statistics, and associations between accident occurrence and participant characteristics were examined using chi-square tests. ResultsOverall, 72.0% of residents experienced at least one accident during the study period. Slipping was the leading cause, and bathrooms and toilets were the most frequent locations. Contusion or bruising was the most common outcome. Mobility limitation was the only factor significantly associated with accident occurrence (p < 0.001), whereas age, gender, marital status, and educational level showed no significant associations. ConclusionsAccidents were common among nursing home residents in Shiraz and were strongly associated with mobility limitation. These findings highlight the importance of addressing functional impairments alongside environmental hazards through targeted ergonomic modifications and mobility-support interventions.

Introduction: Frailty is a dynamic condition associated with increased vulnerability to adverse health outcomes in older adults. While previous research has primarily focused on deficit-based mental health factors, such as depression and loneliness, less is known about the role of positive mental health determinants, including well-being, resilience and social connectedness, in the development and progression of frailty. Understanding both risk and protective factors is essential for informing public health strategies aimed at promoting healthy ageing. This study aims to examine the longitudinal relationship between mental health and frailty in a nationally sampled population of adults aged 50 years and older in Slovenia. Methods and analysis: This longitudinal observational study will collect data at four time points over a two-year period (January 2026-March 2028). A stratified random sample of community-dwelling adults aged 50-84 years will be drawn from the national population registry, with 5,000 individuals invited to participate in the first wave. Frailty, mental health and a set of social, psychological, and health-related factors will be assessed. Data will be analyzed using a combination of descriptive, inferential and longitudinal statistical methods to examine associations between frailty and mental health over time. Potential explanatory factors will also be explored within the longitudinal framework, and additional analyses will assess the impact of attrition. Ethics and dissemination: The study has been approved by the Ethics and Deontology Committee of the National Institute of Public Health. Participation is voluntary, and informed consent will be obtained from all participants. Data will be anonymized and handled in accordance with applicable data protection regulations. Findings will be disseminated through peer-reviewed publications, conference presentations and public health reports to inform strategies for promoting healthy ageing.

Suicide is one of the worlds leading public health problems, with more than 720,000 deaths annually. Suicide has traditionally been studied from an individual perspective. However, research has increasingly highlighted the influence of community-level factors on suicide risk. This study aimed to (1) analyse the spatial distribution of suicide mortality at the provincial level in Spain (2018-2022); (2) perform stratified analyses by sex and age group; and (3) compare suicide risk across different phases of the COVID-19 pandemic. We used data from the Spanish National Institute of Statistics on 19,381 suicide deaths in 47 peninsular provinces between 2018 and 2022. Covariates included sociodemographic (e.g. aging rate, population density), economic (e.g. unemployment, GDP), and environmental (e.g. temperature) indicators. Bayesian hierarchical spatial Poisson regression models were fitted to estimate suicide risk and identify significant contextual variables. The general spatial model revealed a higher risk of suicide in provinces with lower population density, higher aging rates, and lower health expenditure. Other covariates such as gross domestic product, unemployment, or temperature were associated with specific sex or age groups. Suicide risk was highest in the northwestern provinces and lowest in the central regions. Stratified analyses showed similar patterns across gender and age groups, and between time periods, with some variations in spatial distribution. This study reveals significant spatial heterogeneity in suicide risk across Spanish regions, influenced by socio-demographic, economic, and environmental factors. These findings underline the importance of regionally tailored suicide prevention policies, especially in aging and low-density areas with low health investment. Key MessagesWe examined spatial patterns and socioeconomic and environmental determinants of suicide mortality in 50 Spanish provinces between 2018 and 2022. We found persistent geographical inequalities in suicide rates, with higher mortality in low-density provinces and those with older populations, and protective effects associated with health expenditure. These findings highlight the importance of place-based suicide prevention strategies that consider regional disparities and socioeconomic vulnerabilities.

BackgroundEarly life social determinants of health, such as childhood trauma, have implication on adverse health outcomes later in the life course. Our objective was to develop a childhood trauma measure within the Health and Retirement Study (HRS) - a large, diverse, U.S.-based aging cohort. MethodsData from the HRS Psychosocial and Lifestyle Questionnaire [2006-2016] and Life History Survey [2015-2017]) surveys collected thirteen binary items measuring self-reported exposure to early life adversity across the two study questionnaires. Participants who completed both questionnaires and had exposure items available were included in the analyses. Frequencies and percentages for self-reported trauma items are presented for the study sample and by gender and race/ethnicity. Using complete cases, exploratory factor analyses followed by Mokken scale analyses were performed to evaluate the scalability of the childhood trauma items. Predictive criterion validity of the final domains was evaluated with general health and socioeconomic indicators at participant baseline. ResultsAmong the sample with complete childhood trauma data available (n=9,340), most were women (60.7%), White/Non-Hispanic (73.2%), and had a high school/general education degree (54.0%). The most reported childhood traumas were paternal separation [&ge;]6-months (22.8%), parental death (21.4%), sibling death (18.1%), and problematic parental substance use (17.5%). Two scales were formed based on factor analysis and scalability coefficients. The domain measuring disruption of family structure had strong scalability (HT = 0.55) and included living in an orphanage, foster care, parents divorced/separated, [&ge;]6-month from mother and/or father, and grandparents as primary caretakers. A second domain measuring adverse experiences of parent and/or sibling death had moderate scalability (HT = 0.41). Parental substance abuse and physical abuse clustered together in a third domain with weak scalability (HT = 0.39). ConclusionsThe early adversity items available in the HRS offer meaningful domains for which researchers can evaluate childhood trauma exposure in the context of aging outcomes in older adults. In particular, the family structure domain and parental/sibling death demonstrated moderate-to-strong scalability and may have important implications for health trajectories later in life.

Abstract/SummaryFinancial exploitation of older adults is an increasingly prevalent public health concern, yet few have characterized fraud prevalence longitudinally or evaluated whether financial exploitation vulnerability measures prospectively predict fraud outcomes. Using data from the Health and Retirement Study, we examined fraud prevalence across a 14-year period and tested whether the Perceived Financial Vulnerability Scale (PFVS) predicts subsequent fraud victimization among older adults. Fraud prevalence increased steadily over time, rising from 5.0% in 2008 (347 of N=6,920) to a peak of 10.2% in 2022 (448 of N=4,380). Higher PFVS scores measured in 2018 were associated with greater odds of fraud victimization reported in 2022 (OR=1.62, 95% CI [1.25-2.15], p<.001). Most individuals who later reported fraud fell within the highest group of PFVS scores up to five years earlier. Together, these findings highlight financial exploitation as an emerging aging-related vulnerability and support the PFVS as a brief indicator of future fraud risk.

PURPOSEOver 6.9 million Americans above the age of 65 are living with Alzheimers Disease (AD) or related dementias (ADRDs), which are diseases characterized by cognitive decline and structural brain changes associated with accelerated brain aging. Cardiovascular risk factors, in particular hypertension, are well-studied risk factors for AD/ARD. Evidence suggests that the effects of hypertension on cognitive aging may vary by life stage, yet prior studies have focused on the effects of mid- or late-life hypertension or blood pressure, leaving other life stages, including early life, unstudied. However, owing to the logistical complexity of follow-up throughout the life course, cognitive aging cohorts lack early-life blood pressure exposure data and cognitive and brain aging outcome data in mid/late life. When such data are unavailable from any single data source, data fusion methods may be employed to pool two compatible data sources to impute an early-life blood pressure exposure history and produce a synthetic longitudinal cohort in which the associations between early-life blood pressure and mid/late-life cognition and brain aging can be estimated. The purpose of this work is to estimate the association between early-life blood pressure and mid- and late-life cognition and brain aging in a synthetic longitudinal cohort. METHODSWe pooled the Bogalusa Heart Study (BHS) to provide early-life blood pressure data (ages 4-16) and the CARDIA study to provide mid/late-life cognition & brain aging outcome data (ages 58-70) to generate a synthetic longitudinal cohort. Cognition was defined as cognitive domain scores (including executive function, memory, processing speed, and language) calculated by Z-transforming cognitive test scores within each cohort. Global cognition was calculated as the average of these Z-scores. Brain aging was defined using the Spatial Patterns of Atrophy for Recognition of Brain Aging, a measure of age-related brain atrophy using T1-weighted MRI scans. The cohorts overlapped in ages 17-57 for potential matching variables including blood pressure, sociodemographics, and vascular risk factors. Cognition overlapped between ages 41-58. We pooled data by distance-matching many-to-one (BHS to CARDIA) on mediators & confounders of each exposure-disease relationship that overlapped in age of measurement between the two cohorts. These variables included intermediate values of the exposure (blood pressure, ages 17-57), cognition (ages 41-58), in addition to sociodemographic and vascular risk factors. Linear regression models estimated the association between early life blood pressure & cognitive & brain aging outcomes. RESULTSBHS uniquely provided early life blood pressure data (ages 4-16), while CARDIA provided cognitive & brain aging data at ages 58-70. Matching is feasible between the ages of 17-57 on blood pressure, sociodemographics, and vascular risk factors, but 41-57 for cognition. CONCLUSIONSWe our results demonstrate the feasibility & suitability of two US-based cardiovascular cohorts for generating a synthetic lifecourse cohort to estimate early-life blood pressure and its association with mid/late-life cognitive & brain aging outcomes. Future studies should aim to use measures that more closely overlap between both cohorts. Additionally, future studies should interrogate greater spans, such as early life through late life.

ImportanceFrailty is a multisystem syndrome that reflects age-related physiological decline, underscoring the need for more biologically informed risk stratification within frailty assessments. Frailty and heart stress (HS) are individually associated with increased mortality risk, but their combined effects remain practically unexplored. ObjectiveTo evaluate whether the combined exposure to frailty and HS is associated with an increased risk of mortality. Design, Setting, and ParticipantsThis prospective cohort study used data from the US National Health and Nutrition Examination Survey (NHANES) and the Health and Retirement Study (HRS). Participants with complete data on frailty and HS were included. Analyses was performed between May 2025 and October 2025. ExposureFrailty was assessed using three frailty indices (FI) based on self-reported items (FI-Self-report), blood biomarkers (FI-Lab), and their combination (FI-Combined). HS was defined by age-adjusted elevation in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Participants were estimate into four groups according to baseline frailty and HS status. Main Outcomes and MeasuresThe primary outcome was all-cause mortality. Cox proportional hazard models were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsA total of 12,252 participants from NHANES (mean age 49.91 years, 52.18% female), and 9,488 participants from HRS (mean age 69.16 years, 58.97% female) were included. Compared with those having neither frailty nor HS, participants with frailty and/or HS showed significantly elevated mortality risk in both cohorts, with HRs ranging from 1.81 to 5.54. The highest mortality risk was observed in participant with both frailty and HS, the HRs were 3.58 (95% CI: 3.20-4.01) for FI Self Report, 3.43 (95% CI: 3.04-3.86) for FI Lab, and 4.15 (95% CI: 3.70-4.67) for FI Combined in NHANES; the corresponding HRs were 5.02 (95% CI: 4.38-5.76), 4.73 (95% CI: 4.13-5.41), and 5.54 (95% CI: 4.84-6.35) in HRS, respectively. Conclusions and RelevanceCo-occurrence of frailty and HS is common, and jointly associated with increased mortality risk in the general population. These findings support integrating HS into frailty assessments to improve mortality risk stratification and guide targeted interventions. Key PointsQuestion: Is the combination of frailty and heart stress (HS) associated with increased mortality risk? Findings: In this prospective cohort study including 12,252 participants from the US National Health and Nutrition Examination Survey (NHANES) and 9,488 participants from the Health and Retirement Study (HRS), participants with frailty and/or HS exhibited higher risk of all-cause mortality. The greatest mortality risk was found among participant with both frailty and HS. Meaning: These findings indicate that co-occurrence of frailty and HS is associated with increased mortality risk, supporting integration of HS into frailty assessment for risk stratification and intervention.

Childhood socioeconomic position (SEP) can have lifelong effects on health. Many studies have used adult height as a surrogate marker for early-life conditions. In this study, we derived the non-genetic component of height, calculated as the residual from sex-specific standardized height regressed on genetically predicted height, as a surrogate for childhood SEP, using data from the Hispanic Community Healthy Study/Study of Latinos (2008-2011). A positive residual would indicate favorable early-life conditions promoting growth, while a negative residual indicates early-life adversity that may stunt the development. The height residual was associated with early-life variables such as parental education, year of birth, US nativity and age at first migration to the US (50 states/DC), supporting the validity of height residual as a surrogate for early-life conditions. Furthermore, a height residual was positively associated with better cardiovascular health (CVH) and cognitive function among middle-aged and older adults. Interestingly, among <35 years old, the height residual was negatively associated with the "Lifes Essential 8" clinical CVH scores. These results suggest the non-genetic component of height as a surrogate for childhood environment, with predictive value for CVH and cognitive function.

Epigenetic clocks of biological aging have been associated with cognitive impairment and dementia. Less is known about whether they are associated with an older-appearing brain or with an atrophy pattern associated with dementia. We examined associations of five epigenetic clocks measured at baseline with the Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA) and the Alzheimers Disease Pattern Similarity Score (AD-PS) derived from structural MRIs obtained an average of 8 years later among 1,196 older women. Using linear regression models adjusting for relevant covariates, we observed no associations between any epigenetic clock and accelerated brain aging based on SPARE-BA. We observed a significant association between AgeAccelGrim2 and AD-PS ({beta} = 0.015; 95% CI 0.004 to 0.027; p = 0.01). This association appeared to be primarily driven by the association of a DNA methylation marker of smoking pack years with frontal and temporal lobe volumes. AgeAccelGrim2 was not associated with volumes in regions implicated in early AD (hippocampus and entorhinal cortex). Taken together with prior findings, these results suggest that measures of epigenetic and brain age acceleration capture different aspects of biological aging, and that AgeAccelGrim2 is predictive of neurodegenerative changes associated with smoking that increase risk of dementia.

BACKGROUNDLittle is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODSWe examined 5844 women from the Womens Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n=1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n=956, 16.4%); vs. 3) death before age 90 (n=2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. FINDINGSEach standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR=0.66; 95% CI 0.61-0.71), PCGrimAge (OR=0.64; 95% CI 0.59-0.69), PCPhenoAge (OR=0.73; 95% CI 0.68-0.78) and DunedinPACE (OR= 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. INTERPRETATIONAll epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.