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Background: Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought. Methods: We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018. Results: Lower risk was observed across a range of adverse early life outcomes in the grandchildren, including infant mortality (Hazard Ratio (HR) = 0.53, 95% CI [0.36, 0.77]), preterm birth (Odds Ratio (OR) = 0.82, [0.72, 0.93]), small for gestational age (OR = 0.83, [0.76, 0.90]) and neonatal respiratory disorders (OR = 0.77, [0.67, 0.88]). Relative advantages in parental education and maternal smoking were observed in both generations to a similar degree. However, a much smaller reduction in infant mortality was observed in the great-grandchildren (HR = 0.90, [0.70, 1.17]) and benefits across other outcomes were also less consistent, despite persisting socioeconomic and behavioural advantages. Lastly, maternal, and paternal lines of transmission were equipotent in the transmission of infant survival advantages. Conclusions: Descendants of longevity-enriched sibships exhibit a broad health advantage manifesting as early the perinatal period. However, this effect is strongly diluted over successive generations. Our findings suggest that exceptional health and survival may have early developmental components and implicate heritable genetic and or epigenetic factors in their specific transmission.
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This article explores the sexual subjectivity of women of post-reproductive age who seek partners on dating apps. The existing literature highlights the sexual subjectivity and agency of older women as contested and not sufficiently investigated. Even less research has been conducted on changes in the sexual subjectivity of women born in the USSR in the 1960s, with the liberalisation of sexual behaviour. The study is based on 45 interviews with women aged 55 years and over, who were born in the USSR and who now live in Israel, Finland and Russia. In the article, we examine sexual subjectivity as presented in the interviews from a life course perspective. We explain theoretically and empirically how changes in sexual subjectivity are expressed in the light of age and socio-cultural context constraints. Three life stories highlight the accumulation of experience and turning points, such as divorce and migration. They illustrate very different pathways in changing sexual subjectivity, yet all contain three Leitmotifs: desire, security and caring. The expression of post-reproductive female desire can be related to the need to feel secure and enjoy mutual care in sexual relationships. We show that these Leitmotifs shape and are shaped by women's identifications as both sexual objects and subjects, and explore how they relate to different sexual cultures and variations in the socio-sexual positioning of women in Israel, Finland, and Russia.
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Adult and adolescent migrants worldwide, and those arriving in Europe, are an under-immunised group for routine vaccinations due to missed childhood vaccines and doses in their countries of origin, and their subsequent marginalisation from health and vaccination systems. Declining population-level coverage for routine vaccines across Europe, which has accelerated post-pandemic, places these and other under-immunised populations at even greater risk of vaccine-preventable diseases. However, despite clear guidelines around the importance of delivering 'catch-up' vaccination throughout the life-course, migrants are rarely effectively incorporated into routine vaccination programmes on arrival to Europe. These populations have subsequently been involved in outbreaks, including measles and diphtheria, and are missing opportunities to receive more recently introduced vaccines such as HPV to align them with European vaccine schedules. WHO's new Immunization Agenda 2030 places a renewed emphasis on equitable access to vaccine systems and integrating catch-up vaccination for missed vaccines and doses throughout the life-course. In addition, lessons learned and innovations from the COVID-19 pandemic merit further consideration in the design and delivery of more inclusive vaccination programmes. We describe current gaps in policy and practice around life-course vaccination in migrant populations, key factors that drive low vaccine uptake and coverage, and explore the benefits of participatory approaches to designing and delivering interventions with impacted communities, to define new strategies to advance vaccine equity across the Region.
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OBJECTIVES: To determine the effect of social mobility on self-perceived oral health (SPOH) by: (i)characterizing patterns of social mobility from birth to adulthood and (ii)assessing their influence on SPOH among British adults. METHODS: A secondary data analysis of the 1970 British Cohort Study. Data were collected at birth and at 5, 10, 16, 26, 30, 34, 38, 42 and 46 years of age. Social class (SC) was indicated by parental SC from birth to age 16 and own SC from ages 26 to 42. At age 46, SPOH was measured using a single question. Sex, ethnicity, country and residence area were included as potential confounders. Latent class growth analysis (LCGA) was used to identify trajectories of exposure to non-manual SC over time, instead of predetermined categories. RESULTS: LCGA identified four social mobility patterns: stable high, stable low, upwardly mobile and downwardly mobile; the time for the change in SC happening between 16 and 26 years. A total of 9657 participants were included. In the crude model, stable high had lower odds (OR: 0.67, 95% CI: 0.59-0.76), while downward mobility and stable low had higher odds (OR: 1.36, 95% CI: 1.15-1.61 and OR: 1.57, 95% CI: 1.40-1.77) of poor SPOH than upward mobility. These results were corroborated in the fully adjusted model; being female and living in rural areas was also associated with lower odds (OR: 0.64, 95% CI: 0.59-0.71 and OR: 0.90, 95%CI: 0.80-1.00) of poor SPOH. CONCLUSION: Social mobility significantly affects SPOH in British adults. Those in non-manual SC have better SPOH than those in manual SC. When compared to upward mobility, downwardly mobile individuals report bad SPOH more frequently, evidencing that current SC influences oral health in a slightly greater measure than early years SC.
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Established life course approaches suggest that health status in adulthood can be influenced by events that occurred during the prenatal developmental period. Yet, interventions such as diet and lifestyle changes performed during pregnancy have had a small impact on both maternal and offspring health outcomes. Currently, there is a growing body of literature that highlights the importance of maternal health before conception (months or years before pregnancy occurs) for the future health of offspring. While some studies have explored factors such as maternal body composition, nutrition, and lifestyle in this area, location-based environmental and socioeconomic exposures before conception may also contribute to future offspring health. In this line, the study of a patient's geographic history presents a promising avenue. To foster research in this direction, the integration of geospatial health, medical informatics and artificial intelligence techniques offers great potential. Importantly, novel sources of big health data sets such as electronic health records registered at the primary care level provide a unique framework due to its inherent longitudinal nature. Nonetheless, a number of privacy, ethical, and technical challenges need to be overcome for this kind of longitudinal analysis to mature and succeed. In the long-term, we support the vision of incorporating a patient's geographic history into her clinical history to equip clinicians with useful contextual information to explore.
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OBJECTIVES: Advance care planning (ACP), which comprises a living will, durable power of attorney for health care (DPAHC), and end-of-life discussions, is an inherently relational process. However, it is unclear how marital status affects men's and women's ACP over the life course. Drawing on social control and gender as relational frameworks, we examine marital status differences in ACP, and how these patterns differ by gender and age. METHODS: Data are from the 2020 Health and Retirement Study (HRS), a representative sample of U.S. older adults (N = 7,074). We estimate logistic regression models to evaluate whether marital status differences in ACP are moderated by age and gender, and multinomial logistic regressions to examine age and gender differences in DPAHC designations among married parents. Analyses are adjusted for sociodemographic and health covariates. RESULTS: Multivariable analyses revealed significant moderation effects for discussions only. Among married/cohabiting persons, women are more likely than men to have end-of-life discussions, with differences diminishing slightly at oldest ages. Among divorced persons in their 60s and 70s, women are much more likely than men to have had discussions, although this gap converges among the oldest-old. Conversely, young-old widowed men and women are equally likely to have discussions, although women are increasingly likely to do so with advancing age. Men are more likely than women to name their spouse as DPAHC, yet this gap diminishes with age. DISCUSSION: Health care providers can better guide end-of-life consultations if they understand how men's and women's family relationships change with advancing age.
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Using a qualitative design, we explored how life transitions influence Danish adults' physical activity beliefs and behaviour adopting the Theory of Planned Behaviour as a guiding framework. Life story interviews with 42 participants revealed 6 salient life transition periods which affected physical activity behaviour, either in a disruptive way resulting in decreased activity levels or in a facilitative manner, providing opportunities for increased activity engagement. The identified life transition periods uniquely influenced individuals' attitudes, subjective norms and perceived behavioural control (PBC) beliefs, thus affecting motivations toward physical activity. Specifically, starting primary school or a career, forming a romantic relationship, and having a child primarily shaped subjective norm and PBC, while leaving home was especially influential on PBC and retirement on attitudes and PBC. Consistent themes across the transition periods included time constraints and opportunities to be active, supportive social contexts, access to facilities and having a need to be active.
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BACKGROUND: Using cohort analysis to examine the effects of sleep quality on loneliness among older adults from the life course perspective. METHODS: The hierarchical age-period-cohort growth curve model was used to analyze the data from the 2005-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). RESULTS: (1) Loneliness has a 'U' curve relationship with age, but with the rate of increase gradually slowing down. (2) There were significant differences in loneliness across birth cohorts, with younger cohorts having higher predicted loneliness than older cohorts at the same age. (3) The influence of different sleep quality on loneliness showed a trend of increasing with age. (4) There were no significant differences in the impact of sleep quality on loneliness in different cohorts. CONCLUSIONS: This study has identified heterogeneity in loneliness, emphasising the need for a diversified intervention approach. Sleep quality has a protective effect on loneliness and is easy to assess, making it an important intervention tool. In addition, it is imperative to account for the influences of age and cohort effects when formulating intervention strategies.
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BACKGROUND: The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults. METHODS AND RESULTS: We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association "Life's Essential 8," we built a score of ideal CVH at baseline and the 6-year follow-up. Linear mixed-effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (ß for high school versus Subject(s)
Cardiovascular Diseases
, Hispanic or Latino
, Humans
, Male
, Female
, Hispanic or Latino/statistics & numerical data
, Adult
, Middle Aged
, United States/epidemiology
, Cardiovascular Diseases/ethnology
, Cardiovascular Diseases/epidemiology
, Longitudinal Studies
, Socioeconomic Factors
, Health Status
, Social Determinants of Health/ethnology
, Educational Status
, Social Class
, Risk Factors
, Aged
, Health Status Disparities
, Young Adult
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[This corrects the article DOI: 10.3389/fsoc.2024.1393607.].
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OBJECTIVES: An individual's past, and reflections on it, may influence current and future well-being. Recent qualitative studies suggest retirees' recollections about their careers relate to well-being in retirement. We investigated associations between life course events and subjective career evaluations, gender differences in these associations, and their subsequent association with retirement adjustment. METHODS: We used data from three waves (2015, 2018, and 2023) of the (NIDI Pension Panel Study (NPPS), a longitudinal survey of Dutch older workers. Using a sample of 6,109 respondents, we used ordinary least squares (OLS) regression models to investigate associations between employment stability facilitators and inhibitors (e.g., promotion, demotion, unemployment) and personal shocks (e.g., divorce, widowhood) and subjective evaluations of satisfaction with the work and family domains of career between genders. Using a follow-up sample (N=4,106), we employed ordinal logistic regression models to investigate the impact of these baseline subjective evaluations on retirement adjustment at follow-up. RESULTS: Employment stability factors such as demotion and unemployment, and personal shocks such as poor psychological health were associated with subjective evaluations of the work and family career domains. Gender differences in these associations were found. Evaluations in both the work and family domains were associated with retirement adjustment at follow-up. DISCUSSION: Our results demonstrate the importance of life course events on older workers' evaluations of their careers and the long-term impact of subjective career evaluations. Further research is needed to evaluate the predictive utility of these evaluations for other outcomes in older adulthood.
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BACKGROUND: Intermittent fasting, such as during Ramadan, is prevalent among pregnant women. However, the association between Ramadan during pregnancy and offspring health along the life course has not been fully established. OBJECTIVE AND RATIONALE: Fetal programming research indicates that prenatal exposures, particularly during early pregnancy, can cause long-term structural and physiological changes that adversely affect offspring health. Our objective was to systematically identify and assess the evidence regarding Ramadan during pregnancy. SEARCH METHODS: A total of 31 studies were sourced from PubMed, EMBASE, Web of Science, and EconLit. Included studies evaluated outcomes in individuals with prenatal Ramadan exposure, compared to unexposed Muslim controls. Main outcomes were birth weight, gestational length, and sex ratio in newborns; height, mortality, and cognition in children; and disabilities, chronic diseases, and human capital accumulation in adults. Each study was evaluated for risk of bias. The overall quality of evidence was appraised using the GRADE system. Random-effects meta-analyses were conducted for outcomes analyzed in at least three primary studies. OUTCOMES: The initial search identified 2933 articles, 1208 duplicates were deleted. There were 31 publications fulfilled the eligibility criteria for the qualitative synthesis; 22 studies were included in meta-analyses. The overall quality of the evidence was low to moderate and differed by study design and outcome. Among newborns, prenatal Ramadan exposure was not associated with birth weight (mean difference (MD) -3 g (95% CI -18 to 11; I2 = 70%) or the likelihood of prematurity (percentage point difference (PPD) 0.19 (95% CI -0.11 to 0.49; I2 = 0%)). The probability that the newborn is male was reduced (PPD -0.14 (95% CI -0.28 to -0.00; I2 = 0%)). This potentially reflects sex-specific mortality rates resulting from adverse in utero circumstances. In childhood, the exposed performed slightly poorer on cognitive tests (MD -3.10% of a standard deviation (95% CI -4.61 to -1.58; I2 = 51%)). Height among the exposed was reduced, and this pattern was already visible at ages below 5 years (height-for-age z-score MD -0.03 (95% CI -0.06 to -0.00; I2 = 76%)). A qualitative literature synthesis revealed that childhood mortality rates were increased in low-income contexts. In adulthood, the prenatally exposed had an increased likelihood of hearing disabilities (odds ratio 1.26 (95% CI 1.09 to 1.45; I2 = 32%)), while sight was not affected. Other impaired outcomes included chronic diseases or their symptoms, and indicators of human capital accumulation such as home ownership (qualitative literature synthesis). The first trimester emerged as a sensitive period for long-term impacts. WIDER IMPLICATIONS: Despite the need for more high-quality studies to improve the certainty of the evidence, the synthesis of existing research demonstrates that Ramadan during pregnancy is associated with adverse offspring health effects in childhood and especially adulthood, despite an absence of observable effects at birth. Not all health effects may apply to all Muslim communities, which are diverse in backgrounds and behaviors. Notably, moderating factors like daytime activity levels and dietary habits outside fasting hours have hardly been considered. It is imperative for future research to address these aspects. REGISTRATION NUMBER: PROSPERO (CRD42022325770).
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BACKGROUND: Substance use is a public crisis in the U.S. Substance use can be understood as a series of events in the life course, from initiation to mortality. Social Determinants of Health (SDoH) have increasingly been recognized as essential contributors to individuals' health. This scoping review aims to examine available evidence of SDoH impact on the life course of substance use disorder (SUD). METHODS: This study identified peer-reviewed articles that reported longitudinal studies with SDoH factors as independent variables and substance use and disorders as dependent variables from PubMed, Embase, and Web of Science. The reported associations between SDoH and substance use stages over the life course were narratively and graphically summarized. RESULTS: Among the 50 studies identified, ten revealed parental monitoring/support and early childhood education as protective factors, while negative peer influences and neighborhood instability were risk factors of substance use initiation. Nineteen articles reported factors associated with escalation in substance use, including unemployment, neighborhood vulnerability, negative peer influence, violence/trauma, and criminal justice system (CJS) involvement. Ten articles suggested that employment, social support, urban living, and low-barrier medication treatment facilitated treatment participation, while stigma and CJS involvement had negative impact on treatment trajectory. Social support and employment could foster progress in recovery and CJS involvement and unstable housing deterred recovery. Four studies suggested that unemployment, unstable housing, CJS involvement, and lack of social support were associated with overdose and mortality. CONCLUSIONS: This review underscores the influence of social networks and early life experiences on the life course of SUD. Future SDoH research should investigate overdose and mortality and the impact of broader upstream SDoH on SUD. Interventions addressing these social factors are needed to mitigate their detrimental effects on the trajectories of SUD over the life course.
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BACKGROUND: Muscle strength is essential for healthy ageing. Handgrip strength (HGS) has been recommended by expert bodies as the preferred measure of muscle strength, in addition to being considered a strong predictor of overall health. Cross-sectional studies have shown several potential factors associated with HGS, but a systematic review of factors predicting HGS over time has not previously been conducted. The aim of this study is to systematically review the literature on the factors associated with adult HGS [at follow-up(s) or its rate of change] across the life course. METHODS: Searches were performed in MEDLINE via Ebsco, Embase and SPORTDiscus databases. Longitudinal studies assessing potential factors impacting adult HGS over time were included in the analyses. Based on previously established definitions of consistency of results, a semiquantitative analysis was conducted using the proportions of studies supporting correlations with HGS. RESULTS: A total of 117 articles were included in this review. Factors associated with HGS were grouped into 11 domains: demographic, socioeconomic, genetic, early life, body composition, health markers/biomarkers, health conditions, psychosocial, lifestyle, reproductive and environmental determinants. Overall, 103 factors were identified, of which 10 showed consistent associations with HGS over time (i.e., in at least four studies with ≥60% agreement in the direction of association). Factors associated with greater declines in HGS included increasing age, male sex, higher levels of inflammatory markers and the presence of cardiovascular diseases. Education level, medication use, and self-rated health were not associated with the rate of change in HGS. Increased birth weight was associated with a stronger HGS over time, whereas depressive symptoms were linked to a weaker HGS, and smoking habits showed null associations. CONCLUSIONS: Comparison between studies and estimation of effect sizes were limited due to the heterogeneity in methods. Although sex and age may be the main drivers of HGS decline, it is crucial to prioritize modifiable factors such as inflammation and cardiovascular diseases in health interventions to prevent greater losses. Interventions to improve birth weight and mental health are also likely to produce positive effects on muscle strength. Our results point to the complexity of processes involving muscle strength and suggest that the need to better understand the determinants of HGS remains.
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PURPOSE: A powerful aphorism states: "If I hadn't believed it, I wouldn't have seen it!" This challenging notion reminds us how strongly we are influenced by prevailing ideas, and how we interpret things according to current fashions and teachings. MATERIALS AND METHODS: In this paper we present and discuss contemporary perspectives concerning childhood-onset disability and the evolving nature of how people are thinking and acting. We illustrate these ideas by reminding readers of how we have all traditionally been trained and acculturated to think about many dimensions of neurodevelopmental disability ("What?"); reflect on the impact of these ways of thinking in terms of what we have conventionally "seen" and done ("So What?"); and contrast those traditions with contemporary concepts that we believe or know impact the field ("Now What?"). RESULTS: Many of the concepts discussed here will be familiar to readers. In taking this analytically critical perspective we aim to illustrate that by weaving these individual threads together we are able to create a coherent fabric that can serve children with childhood-onset NDD, their families, service providers, the community, and policy-makers. We do not purport to offer a comprehensive view of the whole field. CONCLUSIONS: We encourage readers to consider the integration of these new ways of thinking and acting in our still-evolving field of "childhood-onset disability".
21st-century thinking about childhood-onset neurodisability builds on WHO's ICF framework for health, expanding well beyond traditional primary biomedical foci on diagnosis and management and toward a focus on functioning and belonging.New emphases put family at the centre, attending to family voices and prioritizing family wellbeing as targets for intervention equal to a focus on the child.There is strong emerging evidence to support the value and impact of these broader approaches on overall family functioning and wellbeing.These developments are primarily conceptual rather than technical: they emphasize child and family development, parenting, promotion of functioning, and a life-course approach from the start of intervention.
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We examined three generations (grandparents, mothers, and grandchildren) to assess the association between grandparents' educational attainment and their grandchildren's epigenetic-based age acceleration and whether the association was mediated by parental educational attainment and mothers' life course health-related factors. Mothers were recruited to the NHLBI Growth and Health Study at 9-10 years and followed for 10 years (1987-1998). Mothers were then re-contacted three decades later (ages 37-42) to participate in the National Growth and Health Study (NGHS), and health information from their youngest child (i.e., grandchildren; N = 241, ages 2-17) was collected, including their saliva samples to calculate epigenetic age. Five epigenetic-based age acceleration measures were included in this analysis, including four epigenetic clock age accelerations (Horvath, Hannum, GrimAge, and PhenoAge) and DunedinPACE. Grandparents reported their highest education during the initial enrollment interviews. Parental educational attainment and mothers' life course health-related factors (childhood BMI trajectories, adult cardiovascular health behavioral risk score, and adult c-reactive protein) are included as mediators. Grandparents' education was significantly associated with Horvath age acceleration (b = -0.32, SE = 0.14, p = 0.021). Grandchildren with college-degree grandparents showed significantly slower Horvath age accelerations than those without college degrees. This association was partially mediated by parental education and mothers' health-related factors, especially adult cardiovascular health behavioral risk score and CRP, but not mothers' childhood BMI trajectory. This ability to conserve the speed of biological aging may have considerable consequences in shaping health trajectories across the lifespan.
Subject(s)
Educational Status , Grandparents , Humans , Grandparents/psychology , Female , Child , Adult , Male , Adolescent , Child, Preschool , Mothers/psychology , Mothers/statistics & numerical data , AgingABSTRACT
Objectives: To investigate the effects of age, period, and cohort on the trends of depression; and to examine the influence of these three temporal effects on residential disparities in depression. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS) during 2011 to 2020, involving 77,703 respondents aged 45 years old and above. The measurement of depressive symptoms was the score of 10-question version of the Center for Epidemiologic Studies Depression Scale (CES-D 10). The hierarchical age-period-cohort cross-classified random effects models were conducted to examine trends in depressive symptoms related to age, period and cohort. Results: CES-D scores increased with age and slightly decreased at older age. The cohort trends mostly increased except for a downward trend among those born in 1950s. As for the period effect, CES-D scores decreased gradually from 2011 to 2013 followed by a upward trend. Rural residents were associated with higher level of depression than those live in urban area. These residence gaps in depression enlarged before the age of 80, and then narrowed. The urban-rural disparities in CES-D scores gradually diminished across cohorts, while the corresponding period-based change in urban-rural gaps was not significant. Conclusion: When age, period, cohort factors are considered, the age effects on depression dominated, and the period and cohort variations were relatively small. The residence disparities in depression reduced with successive cohorts, more attention should be paid to the worsening depression condition of younger cohorts in urban areas.
Subject(s)
Depression , Humans , China/epidemiology , Depression/epidemiology , Aged , Male , Female , Middle Aged , Longitudinal Studies , Age Factors , Aged, 80 and over , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Cohort Effect , East Asian PeopleABSTRACT
OBJECTIVES: Due to statistical challenges in disentangling the mobility effect (i.e., intergenerational educational mobility) from the position effect (i.e., parental and person's own education), the impact of intergenerational educational mobility on cognitive function remains unclear. We employed a novel approach to identify the mobility effect and investigate the net impact of intergenerational educational mobility on heterogeneous patterns of cognition among middle-aged and older adults in China. METHODS: Participants aged 45 and older were recruited from the China Health and Retirement Longitudinal Study, a population-based prospective cohort study between 2011 and 2018. We identified cognitive trajectories using the growth mixture model (GMM) and subsequently employed the mobility contrast model (MCM) to examine the effects of intergenerational educational mobility on cognitive patterns stratified by gender. RESULTS: Almost two thirds of respondents experienced intergenerational educational mobility, and 55% experienced upward mobility. Men had a higher rate of upward mobility than women. Three population-based cognitive patterns were identified: the low cognitive function with decline group (28%), the moderate cognitive function group (47%), and the high cognitive function group (26%). MCM analysis revealed that both upward and downward intergenerational educational mobility negatively affected cognitive trajectory patterns, extending beyond the influence of individuals' current and parental education. DISCUSSION: In future research, the impact of mobility can be studied in longitudinal data sets by combining the GMM and MCM approaches. The net negative effect of intergenerational educational mobility on cognitive trajectory patterns indicates that it should be recognized as an independent predictor of cognitive decline.
Subject(s)
Cognition , Educational Status , Humans , Male , Female , Aged , Longitudinal Studies , China/epidemiology , Middle Aged , Cognition/physiology , Prospective Studies , Intergenerational Relations , Sex Factors , Cognitive Dysfunction/epidemiology , East Asian PeopleABSTRACT
BACKGROUND: Both genetic predispositions and exposures to stressors have collectively contributed to the development of major depressive disorder (MDD). To deep dive into their roles in MDD, our study aimed to examine which susceptible gene expression interacts with various dimensions of stressors in the MDD risk among a large population cohort. METHODS: Data analyzed were from a longitudinal community-based cohort from Southwest Montreal, Canada (N = 1083). Latent profile models were used to identify distinct patterns of stressors for the study cohort. A transcriptome-wide association study (TWAS) method was performed to examine the interactive effects of three dimensions of stressors (threat, deprivation, and cumulative lifetime stress) and gene expression on the MDD risk in a total of 48 tissues from GTEx. Additional analyses were also conducted to further explore and specify these associations including colocalization, and fine-mapping analyses, in addition to enrichment analysis investigations based on TWAS. RESULTS: We identified 3321 genes linked to MDD at the nominal p-value <0.05 and found that different patterns of stressors can amplify the genetic susceptibility to MDD. We also observed specific genes and pathways that interacted with deprivation and cumulative lifetime stressors, particularly in specific brain tissues including basal ganglia, prefrontal cortex, brain amygdala, brain cerebellum, brain cortex, and the whole blood. Colocalization analysis also identified these genes as having a high probability of sharing MDD causal variants. LIMITATIONS: The study cohort was composed exclusively of individuals of Caucasians, which restricts the generalizability of the findings to other ethnic population groups. CONCLUSIONS: The findings of the study unveiled significant interactions between potential tissue-specific gene expression × stressors in the MDD risk and shed light on the intricate etiological attributes of gene expression and specific stressors across the lifespan in MDD. These genetic and environmental attributes in MDD corroborate the vulnerability-stress theory and direct future stress research to have a closer examination of genetic predisposition and potential involvements of omics studies to specify the intricate relationships between genes and stressful environments.