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Aims: About 10%-30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state., Materials and Methods: We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGS BMI ) differed cross-sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO., Results: Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGS BMI . The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGS BMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07)., Conclusions: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for chronological age, sex, education, and smoking. We assessed curvilinear associations of BMI and chronological age with physiological age, and interactions between BMI, MetS, and chronological age. We found a significant three-way interaction between BMI, MetS, and chronological age on FI (p-interaction = 0·006), not FAI. Consequently, we stratified FI analyses by age: < 65, 65-85, and ≥ 85 years, and modeled FAI across ages. Except for FI at ages ≥ 85, BMI had U-shaped associations with FI and FAI, where BMI around 26-28 kg/m 2 was associated with the lowest physiological age. MetS was associated with higher FI and FAI, except for FI at ages < 65, and modified the BMI-FI association at ages 65-85 (p-interaction = 0·02), whereby the association between higher BMI levels and FI was stronger in individuals with MetS. Age modified the MetS-FI association in ages ≥ 85, such that it was stronger at higher ages (p-interaction = 0·01). Low BMI, high BMI, and metabolic syndrome were associated with higher physiological age, contributing to overall health status among older individuals and potentially accelerating aging., (© 2023. The Author(s).)

Introduction: Metabolically healthy obesity may be a transient phenotype, but studies with long follow-up, especially covering late-life, are lacking. We describe conversions between cross-categories of body mass index (BMI) and metabolic health in 786 Swedish twins with up to 27 years of follow-up, from midlife to late-life., Methods: Metabolic health was defined as the absence of metabolic syndrome (MetS). We first visualized conversions between BMI-metabolic health phenotypes in 100 individuals with measurements available at ages 50-64, 65-79, and ≥80. Next, we modeled conversion in metabolic health status by BMI category in the full sample using Cox proportional hazards regression., Results: The proportion of individuals with MetS and with overweight or obesity increased with age. However, one-fifth maintained a metabolically healthy overweight or obesity across all three age categories. Among those metabolically healthy at baseline, 59% converted to MetS during follow-up. Conversions occurred 56% more often among individuals with metabolically healthy obesity, but not overweight, compared to normal weight. Among those with MetS at baseline, 60% regained metabolic health during follow-up, with no difference between BMI categories., Conclusions: Conversions between metabolically healthy and unhealthy status occurred in both directions in all BMI categories. While conversions to MetS were more common among individuals with obesity, many individuals maintained or regained metabolic health during follow-up., (© 2023. The Author(s).)

Background: The organizational principle of remaining at home has offset care from the hospital to the home of the older person where care from formal and informal caregivers is needed. Globally, formal care is often organized to handle singular and sporadic health problems, leading to the need for several health care providers. The need for an integrated care model was therefore recognized by health care authorities in one county in Sweden, who created a cross-organisational integrated care model to meet these challenges. The Mobile integrated care model with a home health care physician (MICM) is a collaboration between regional and municipal health care. Descriptions of patients' and next of kin's experiences of integrated care is however lacking, motivating exploration., Method: A qualitative thematic study. Data collection was done before the patients met the MICM physician, and again six months later., Results: The participants expected a sense of relief when admitted to MICM, and hoped for shared responsibility, building a personal contact and continuity but experienced lack of information about what MICM was. At the follow-up interview, participants described having an easier daily life. The increased access to the health care personnel (HCP) allowed participants to let go of responsibility, and created a sense of safety through the personalised contact and continuity. However, some felt ignored and that the personnel teamed up against the patient. The MICM structure was experienced as hierarchical, which influenced the possibility to participate. However, the home visits opened up the possibility for shared decision making., Conclusion: Participants had an expectation of receiving safe and coherent health care, to share responsibility, personal contact and continuity. After six months, the participants expressed that MICM had provided an easier daily life. The direct access to HCP reduced their responsibility and they had created a personalised contact with the HCP and that the individual HCP mattered to them, which could be perceived as in line with the goals in the shift to local health care. The MICM was experienced as a hierarchic structure with impact on participation, indicating that all dimensions of person-centred care were not fulfilled., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI)., Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40-64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGS BMI ) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGS BMI . Co-twin control models were applied to adjust for genetic influences not captured by the PGS BMI ., Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGS BMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGS BMI , respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGS BMI . Results were similar when obesity was measured in late-life, but suffered from low power., Interpretation: Obesity was associated with CVD regardless of PGS BMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGS BMI , still influence the associations., Funding: The Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman's Foundation; Foundation for Geriatric Diseases at Karolinska Institutet; the Swedish Research Council for Health, Working Life and Welfare; the Swedish Research Council; and the National Institutes of Health., Competing Interests: JJ reports grant funding paid to their institution from the 10.13039/501100004359Swedish Research Council (grant 2018-02077), 10.13039/501100002341Academy of Finland (grant 349335), 10.13039/501100006306Sigrid Jusélius Foundation, 10.13039/100010114Yrjö Jahnsson Foundation, and 10.13039/501100008413Instrumentarium Science Foundation. CAR reports honorarium from the National Institute on Aging and grant funding from the 10.13039/100000002National Institutes of Health (grants NIH 1R01 DA054087, NIH 2R01 AG046938, NIH 2R01 AG050595, NIH 1R01 AG059329, NIH 1RF1 AG058068, NIH 1R01 AG077742, and NIH 1R01 AG053217). IKK reports payments to their institution from the Karolinska Institutet Research Foundation (grant 2022-01718) and Eurolife (mobility grant). IKK also reports payment via a Promising Researcher Award from The Nordic Gerontological Federation. All other authors declare no competing interests., (© 2023 The Author(s).)

While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life. Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40-64, n = 5999) or late-life (age 65-90, n = 7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses. Age was used as the underlying time scale, and sex and education included as covariates in all models. Fasting status was included as a covariate in models of lipids. One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2-52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1-14%) lower dementia risk. The association was partly mediated by higher CRP, and suppressed when high-density lipoprotein levels were low. In conclusion, the negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, with no evidence of mediation through inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body's inflammatory response and lipid homeostasis is intact., (© 2022. The Author(s).)

Abstract: Higher body mass and obesity are associated with bodily pain, and rates of chronic pain increase among older adults. Most past studies are cross-sectional, precluding determination of the temporal relationship between body mass and pain. A longitudinal study of body mass and pain among middle-aged adults found that higher body mass index (BMI) led to greater lower back pain. No longitudinal study of BMI and pain has been conducted among adults older than 70 years. This study used dual change score models to determine the directional relationship between BMI and bodily pain in a sample of middle-aged and older adults. Participants (n = 1889) from the Swedish Twin Registry (baseline age range 40-93 years) completed at least 1 nurse assessment of BMI and self-report ratings of pain interference and joint pain. Pain interference was not associated with BMI, but joint pain was analyzed in univariate and bivariate models, with dual change score models modeling the relationship of BMI and joint pain across age, both independently and as part of bivariate relationships. The results indicated a reciprocal relationship between BMI and joint pain, but joint pain generally led to changes in BMI. In addition, the relationship changed with age, until approximately age 80 years, increasing joint pain contributed to higher BMI, but after that time increasing joint pain contributed to lower BMI. In addition, sex differences in the relationship between BMI and pain appeared after age 70 years. Thus, joint pain contributes to changes in BMI among middle-aged and older adults, but the relationship may change by age and sex., (Copyright © 2022 International Association for the Study of Pain.)

Aims: There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long-term morbidity and mortality, and to investigate whether cognitive ability plays a role in long-term morbidity and mortality risk., Methods: In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan-Meier analyses with log-rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated., Results: Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56-5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27-9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79-5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes., Conclusions: In this historical cohort study with 60 years of follow-up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations., (© 2022. The Author(s).)

Background: An increasing older population, along with the organizational principle of remaining at home, has moved health care from institutions into the older person's home, where several health care providers facilitate care. The Mobile Integrated Care Model strives to provide cost-efficient, coherent, person-centered health care in the home. In the integrated care team, where the home health care physician is the medical authority, several health care professions work across organizational borders. Therefore, the aim of this study was to describe Home Health Care Physicians perceptions of working and providing health care in the Mobile Integrated Care Model, as well as perceptions of participating in and forming health care., Methods: A phenomenographic qualitative study design, with semi-structured interviews using an interview guide., Results: Working within Mobile Integrated Care Model was a different way of working as a physician. The physicians' role was to support the patient by making safe medical decisions. Physicians described themselves as a piece in the team puzzle, where the professional knowledge of others was crucial to give quality health care. Being in the patients' homes was expressed as adding a unique dimension in the provision of health care, and the physicians learned more about the patients by meeting them in their homes than at an institution. This aided the physicians in respecting patient autonomy in medical decision making, even though the physicians sometimes disregarded patient autonomy in favor of their own medical experience. There was a divided view on next of kin participation among the home health care physicians, ranging from always including to total absence of involving next of kin in decision making., Conclusions: The home health care physicians described the Mobile Integrated Care Model as the best way to work, but there was still a need for additional resources and structure when working in different organizations. The need for full-time employment, additional time or hours, more equipment, access to each other's medical records, and additional collaboration with other health care providers were expressed, which could contribute to increased work satisfaction and facilitate further development of person-centered care in the Mobile Integrated Care Model., (© 2022. The Author(s).)

Background: There is robust evidence that in midlife, higher body mass index (BMI) and metabolic syndrome (MetS), which often co-exist, are associated with increased mortality risk. However, late-life findings are inconclusive, and few studies have examined how metabolic health status (MHS) affects the BMI-mortality association in different age categories. We, therefore, aimed to investigate how mid- and late-life BMI and MHS interact to affect the risk of mortality., Methods: This cohort study included 12,467 participants from the Swedish Twin Registry, with height, weight, and MHS measures from 1958-2008 and mortality data linked through 2020. We applied Cox proportional hazard regression with age as a timescale to examine how BMI categories (normal weight, overweight, obesity) and MHS (identification of MetS determined by presence/absence of hypertension, hyperglycemia, low HDL, hypertriglyceridemia), independently and in interaction, are associated with the risk of all-cause mortality. Models were adjusted for sex, education, smoking, and cardiovascular disease., Results: The midlife group included 6,252 participants with a mean age of 59.6 years (range = 44.9-65.0) and 44.1% women. The late-life group included 6,215 participants with mean age 73.1 years (65.1-95.3) and 46.6% women. In independent effect models, metabolically unhealthy status in midlife increased mortality risks by 31% [hazard ratio 1.31; 95% confidence interval 1.12-1.53] and in late-life, by 18% (1.18;1.10-1.26) relative to metabolically healthy individuals. Midlife obesity increased the mortality risks by 30% (1.30;1.06-1.60) and late-life obesity by 15% (1.15; 1.04-1.27) relative to normal weight. In joint models, the BMI estimates were attenuated while those of MHS were less affected. Models including BMI-MHS categories revealed that, compared to metabolically healthy normal weight, the metabolically unhealthy obesity group had increased mortality risks by 53% (1.53;1.19-1.96) in midlife, and across all BMI categories in late-life (normal weight 1.12; 1.01-1.25, overweight 1.10;1.01-1.21, obesity 1.31;1.15-1.49). Mortality risk was decreased by 9% (0.91; 0.83-0.99) among those with metabolically healthy overweight in late-life., Conclusions: MHS strongly influenced the BMI-mortality association, such that individuals who were metabolically healthy with overweight or obesity in mid- or late-life did not carry excess risks of mortality. Being metabolically unhealthy had a higher risk of mortality independent of their BMI., (© 2022. The Author(s).)

Background: Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available., Objective: We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results., Methods: Using 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available., Results: Results indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis., Conclusion: This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.

Background: frailty shows an upward trajectory with age, and higher levels increase the risk of mortality. However, it is less known whether the shape of frailty trajectories differs by age at death or whether the rate of change in frailty is associated with mortality., Objectives: to assess population frailty trajectories by age at death and to analyse whether the current level of the frailty index (FI) i.e. the most recent measurement or the person-specific rate of change is more predictive of mortality., Methods: 3,689 individuals from three population-based cohorts with up to 15 repeated measurements of the Rockwood frailty index were analysed. The FI trajectories were assessed by stratifying the sample into four age-at-death groups: <70, 70-80, 80-90 and >90 years. Generalised survival models were used in the survival analysis., Results: the FI trajectories by age at death showed that those who died at <70 years had a steadily increasing trajectory throughout the 40 years before death, whereas those who died at the oldest ages only accrued deficits from age ~75 onwards. Higher level of FI was independently associated with increased risk of mortality (hazard ratio 1.68, 95% confidence interval 1.47-1.91), whereas the rate of change was no longer significant after accounting for the current FI level. The effect of the FI level did not weaken with time elapsed since the last measurement., Conclusions: Frailty trajectories differ as a function of age-at-death category. The current level of FI is a stronger marker for risk stratification than the rate of change., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To study if declining cognition drives weight loss in preclinical dementia, we examined the longitudinal association between body mass index (BMI) and cognitive abilities in individuals who did or did not later develop dementia., Methods: Using data from individuals spanning age 50 to 89, we applied dual change score models separately in individuals who remained cognitively intact (n = 1498) and those who were diagnosed with dementia within 5 years of last assessment (n = 459)., Results: Among the cognitively intact, there was a bidirectional association: Stable BMI predicted stable cognition and vice versa. Among individuals who were subsequently diagnosed with dementia, the association was unidirectional: Higher BMI predicted declining cognition but cognition did not predict change in BMI., Discussion: Although BMI and cognition stabilized each other when cognitive functioning was intact, this buffering effect was missing in the preclinical dementia phase. This finding indicates that weight loss in preclinical dementia is not driven by declining cognition., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Background: Epigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities. We conducted an epigenome-wide association study of leukocyte DNA methylation in relation to level and change in cognitive abilities, from midlife through late life in 535 Swedish twins., Results: Methylation levels were measured with the Infinium Human Methylation 450 K or Infinium MethylationEPIC array, and all sites passing quality control on both arrays were selected for analysis (n = 250,816). Empirical Bayes estimates of individual intercept (age 65), linear, and quadratic change were obtained from latent growth curve models of cognitive traits and used as outcomes in linear regression models. Significant sites (p < 2.4 × 10 -7 ) were followed up in between-within twin pair models adjusting for familial confounding and full-growth modeling. We identified six significant associations between DNA methylation and level of cognitive abilities at age 65: cg18064256 (PPP1R13L) with processing speed and spatial ability; cg04549090 (NRXN3) with spatial ability; cg09988380 (POGZ), cg25651129 (-), and cg08011941 (ENTPD8) with working memory. The genes are involved in neuroinflammation, neuropsychiatric disorders, and ATP metabolism. Within-pair associations were approximately half that of between-pair associations across all sites. In full-growth curve models, associations between DNA methylation and cognitive level at age 65 were of small effect sizes, and associations between DNA methylation and longitudinal change in cognitive abilities of very small effect sizes., Conclusions: Leukocyte DNA methylation was associated with level, but not change in cognitive abilities. The associations were substantially attenuated in within-pair analyses, indicating they are influenced in part by genetic factors.

Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGS BMI ). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life. The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGS BMI compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline.

Background: Frailty is a strong predictor of adverse outcomes. However, longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the factors associated with the level and rate of change in FI., Methods: An age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N = 1,842; aged 29-102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave., Results: A bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one's co-twin during childhood, smoking, poor social support, and low physical activity were associated with a higher FI at age 65, with underweight having the largest effect size. When tested as time-varying covariates, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65., Conclusions: Factors associated with the level and rate of change in frailty are largely actionable and could provide targets for intervention. As deviations from normal weight showed the strongest associations with frailty, future public health programs could benefit from monitoring of individuals with abnormal BMI, especially those who are underweight., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: Body fat, measured with body mass index (BMI), and obesity are associated with depressive symptoms. Among younger adults there is stronger evidence of obesity leading to depressive symptoms than of depressive symptoms leading to obesity, but the temporal relationship is unknown among older adults. This study utilized dual-change-score models (DCSMs) to determine the directional relationship between body mass and depressive symptoms among older adults., Method: Participants (n = 1,743) from the Swedish Twin Registry (baseline age range 50-96 years) completed at least one assessment of BMI (nurse measurement of height and weight) and the Center for Epidemiologic Studies-Depression scale (CESD). More than half the sample completed 3 or more assessments, scheduled at intervals of 2-4 years. DCSMs modeled the relationship of BMI and CESD across age, both independently and as part of bivariate relationships., Results: Depressive symptoms contributed to subsequent changes in BMI after age 70, while BMI contributed to subsequent changes in depressive symptoms after age 82. Thus, there is a reciprocal relationship that may change with age. The effect was more pronounced for women., Discussion: The association of BMI and depressive symptoms is bidirectional among older adults, and it appears to be affected by both age and sex., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a 2  = 0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c 2  = 0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a 2  = 0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a 2  = 0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c 2  = 0.31; 0.29-0.33 and c 2  = 0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

Background: While a high body mass index (BMI) in midlife is associated with higher risk of dementia, high BMI in late-life may be associated with lower risk. This study combined genetic designs with longitudinal data to achieve a better understanding of this paradox., Methods: We used longitudinal data from 22,156 individuals in the Swedish Twin Registry (STR) and 25,698 from the Health and Retirement Study (HRS). The STR sample had information about BMI from early adulthood through late-life, and the HRS sample from age 50 through late-life. Survival analysis was applied to investigate age-specific associations between BMI and dementia risk. To examine if the associations are influenced by genetic susceptibility to higher BMI, an interaction between BMI and a polygenic score for BMI (PGS BMI ) was included in the models and results stratified into those with genetic predisposition to low, medium, and higher BMI. In the STR, co-twin control models were applied to adjust for familial factors beyond those captured by the PGS BMI ., Results: At age 35-49, 5 units higher BMI was associated with 15% (95% CI 7-24%) higher risk of dementia in the STR. There was a significant interaction (p = 0.04) between BMI and the PGS BMI , and the association present only among those with genetic predisposition to low BMI (HR 1.38, 95% CI 1.08-1.78). Co-twin control analyses indicated genetic influences. After age 80, 5 units higher BMI was associated with 10-11% lower risk of dementia in both samples. There was a significant interaction between late-life BMI and the PGS BMI in the STR (p = 0.01), but not the HRS, with the inverse association present only among those with a high PGS BMI (HR 0.70, 95% CI 0.52-0.94) . No genetic influences were evident from co-twin control models of late-life BMI., Conclusions: Not only does the association between BMI and dementia differ depending on age at BMI measurement, but also the effect of genetic influences. In STR, the associations were only present among those with a BMI in opposite direction of their genetic predisposition, indicating that the association between BMI and dementia across the life course might be driven by environmental factors and hence likely modifiable.

Background: There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors., Methods: We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between-within models to study associations within twin pairs, thus adjusting for genetic factors., Results: Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites., Conclusion: Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Background: Despite advances in life expectancy, low socioeconomic status is associated with a shorter lifespan. This study was conducted to investigate socioeconomic differences in mortality by comparing preventable with non-preventable causes of death in 39 506 participants from the Swedish Twin Registry born before 1935., Methods: Childhood social class, own education, own social class and social mobility were used as separate indicators of socioeconomic status. These data were linked to the Swedish Cause of Death Register. Cause of death was categorized as preventable or non-preventable mortality according to indicators presented in the Avoidable Mortality in the European Union (AMIEHS) atlas. Using Cox proportional hazard models, we tested the association between the socioeconomic measures and all-cause mortality, preventable mortality and non-preventable mortality. Additional co-twin control analyses indicated whether the associations reflected genetic confounding., Results: The social gradient for mortality was most prominent for the adult socioeconomic measures. There was a social gradient in both preventable mortality and non-preventable mortality, but with an indication of a moderately stronger effect in preventable causes of death. In analyses of social mobility, those who experienced life-time low socioeconomic status (SES) or downward social mobility had an increased mortality risk compared with those with life-time high SES and upward social mobility. Adjustments for genetic confounding did not change the observed associations for education, social class or social mobility and mortality. In the co-twin control analyses of reared-apart twins, the association between childhood social class and mortality weakened, indicating possible genetic influences on this association., Conclusions: Our results indicate that there is an association between low adult socioeconomic status and increased mortality independent of genetic endowment. Thus, we do not find support for indirect social selection as the basis for mortality inequalities in Sweden., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.)

This study aimed to investigate the association between shift work and incident dementia in two population-based cohorts from the Swedish Twin Registry (STR). The STR-1973 sample included 13,283 participants born 1926-1943 who received a mailed questionnaire in 1973 that asked about status (ever/never) and duration (years) of shift work employment. The Screening Across the Lifespan Twin (SALT) sample included 41,199 participants born 1900-1958 who participated in a telephone interview in 1998-2002 that asked about night work status and duration. Dementia diagnoses came from Swedish patient registers. Cox proportional-hazards regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Potential confounders such as age, sex, education, diabetes, cardiovascular disease and stroke were included in adjusted models. In genotyped subsamples (n = 2977 in STR-1973; n = 10,366 in SALT), APOE ε4 status was considered in models. A total of 983 (7.4%) and 1979 (4.8%) dementia cases were identified after a median of 41.2 and 14.1 years follow-up in the STR-1973 and SALT sample, respectively. Ever shift work (HR 1.36, 95% CI 1.15-1.60) and night work (HR 1.12, 95% CI 1.01-1.23) were associated with higher dementia incidence. Modest dose-response associations were observed, where longer duration shift work and night work predicted increased dementia risk. Among APOE ε4 carriers, individuals exposed to ≥ 20 years of shift work and night work had increased dementia risk compared to day workers. Findings indicate that shift work, including night shift work, compared to non-shift jobs is associated with increased dementia incidence. Confirmation of findings is needed.

Background: Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background., Methods and Findings: The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18-69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade., Conclusions: Smoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2., Competing Interests: TK reports personal consultation fees from Pfizer Finland, during the conduct of the study but outside of this study. JK reports grants from the Academy of Finland and the Sigrid Juselius Foundation, during the conduct of the study, and personal fees from Pfizer Inc., outside the submitted study. AB reports working in the HealthTwiSt GmbH but the company did not have any impact on this study. FI reports grants from JSPS KAKENHI JP (23593419,16K15978), during the conduct of the study. MG reports grants from the National Institutes of Health, during the conduct of the study, and other grants from National Institutes of Health, outside the submitted work period. All other authors have nothing to declare. None of the funders played a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials. None of the commercial affiliations affects our adherence to PLOS ONE policies on sharing data and materials. The specific roles of authors with commercial affiliations (AB, JK, TK) are articulated in the 'author contributions' section. The corresponding author had full access to all of the data in the study and had final responsibility for the decision to submit the paper for publication.

Age moderation of genetic and environmental contributions to Digits Forward, Digits Backward, Block Design, Symbol Digit, Vocabulary, and Synonyms was investigated in a sample of 14,534 twins aged 26 to 98 years. The Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium contributed the sample, which represents nine studies from three countries (USA, Denmark, and Sweden). Average test performance was lower in successively older age groups for all tests. Significant age moderation of additive genetic, shared environmental, and non-shared environmental variance components was observed, but the pattern varied by test. The genetic contribution to phenotypic variance across age was smaller for both Digit Span tests, greater for Synonyms, and stable for Block Design and Symbol Digit. The non-shared environmental contribution was greater with age for the Digit Span tests and Block Design, while the shared environmental component was small for all tests, often more so with age. Vocabulary showed similar age-moderation patterns as Synonyms, but these effects were nonsignificant. Findings are discussed in the context of theories of cognitive aging.

Background: Diabetes has been linked to dementia risk; however, the cognitive trajectories in older adults with diabetes remain unclear. We aimed to investigate the effect of prediabetes and diabetes on cognitive trajectories among cognitively intact older adults in a long-term follow-up study., Methods: Within the Swedish Adoption/Twin Study of Aging, 793 cognitively intact older adults aged ≥50 were identified at baseline and followed for up to 23 years. Based on standardized scores from 11 cognitive tests, administered at baseline and up to seven follow-ups, four cognitive domains (verbal abilities, spatial/fluid, memory, perceptual speed) were identified by principal-component analysis. Prediabetes was defined according to blood glucose levels in diabetes-free participants. Diabetes was ascertained based on self-report, hypoglycemic medication use and blood glucose levels. Data were analyzed with linear mixed-effect models adjusting for potential confounders., Results: At baseline, 68 participants (8.6%) had prediabetes and 45 (5.7%) had diabetes. Compared to diabetes-free individuals, people with diabetes had a steeper decline over time in perceptual speed and verbal abilities. The annual declines in these domains were greater than the annual decline in memory. Prediabetes was associated with lower performance in memory in middle-age, but also associated with a less steep memory decline over the follow-up., Conclusions: Diabetes is associated with a faster decline in perceptual speed and verbal abilities, while prediabetes is associated with lower memory performance in middle-age. However, the detrimental effects of hyperglycemia seem to not affect memory over time., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Research indicate that cognitive impairment might be related to hospitalization, but little is known about these effects over time., Objective: To assess cognitive change before and after hospitalization among older adults in a population-based longitudinal study with up to 25 years of follow-up., Method: A longitudinal study on 828 community living men and women aged 50-86 from the Swedish Adoption/Twin Study of Ageing (SATSA) were linked to The Swedish National Inpatient Register. Up to 8 assessments of cognitive performance (general cognitive ability, verbal, spatial/fluid, memory, and processing speed) from 1986 to 2010 were available. Latent growth curve modelling was used to assess the association between cognitive performance and hospitalization including spline models to analyse cognitive trajectories pre- and post-hospitalization., Results: A total of 735 persons (89%) had at least one hospital admission during the follow-up. Mean age at first hospitalization was 70.2 (±9.3)years. Persons who were hospitalized exhibited a lower mean level of cognitive performance in general ability, processing speed and spatial/fluid ability compared with those who were not hospitalized. The two-slope models revealed steeper cognitive decline before hospitalization than after among those with at least one hospitalization event, as compared to non-hospitalized persons who showed steeper cognitive decline after the centering age of 70 years., Conclusions: Persons being hospitalized in late life have lower cognitive performance across all assessed domains. The results indicate that the main decline occurs before the hospitalization, and not after. This might indicate that when you get treatment you also benefit cognitively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Population-based health registers are potential assets in epidemiological research; however, the quality of case ascertainment is crucial., Objective: To compare the case ascertainment of dementia, from the National Patient Register (NPR) and the Cause of Death Register (CDR) with dementia diagnoses from six Swedish population based studies., Methods: Sensitivity, specificity, and positive predictive value (PPV) of dementia identification in NPR and CDR were estimated by individual record linkage with six Swedish population based studies (n = 19,035). Time to detection in NPR was estimated using data on dementia incidence from longitudinal studies with more than two decades of follow-up., Results: Barely half of the dementia cases were ever detected by NPR or CDR. Using data from longitudinal studies we estimated that a record with a dementia diagnosis appears in the NPR on average 5.5 years after first diagnosis. Although the ability of the registers to detect dementia cases was moderate, the ability to detect non-dementia cases was almost perfect (99%). When registers indicate that there is a dementia diagnosis, there are very few instances in which the clinicians determined the person was not demented. Indeed, PPVs were close to 90%. However, misclassification between dementia subtype diagnoses is quite common, especially in NPR., Conclusions: Although the overall sensitivity is low, the specificity and the positive predictive value are very high. This suggests that hospital and death registers can be used to identify dementia cases in the community, but at the cost of missing a large proportion of the cases.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Objectives The few studies of shift work and late life cognitive functioning have yielded mixed findings. The aim of the present study is to estimate the association between shift-work experience and change in cognitive performance before and after retirement age among older adults who were gainfully employed. Methods Five hundred and ninety five participants with no dementia were followed up for a mean of 17.6 standard deviation (SD) 8.8 years from a Swedish population-based sample. Participants had self-reported information on any type of shift-work experience (ever/never) in 1984 and measures of cognitive performance (verbal, spatial, memory, processing speed, and general cognitive ability) from up to 9 waves of cognitive assessments during 1986-2012. Night work history (ever/never) from 1998-2002 was available from a subsample (N=320). Early adult cognitive test scores were available for 77 men. Results In latent growth curve modeling, there were no main effects of "any-type" or night shift work on the mean scores or rate of change in any of the cognitive domains. An interaction effect between any-type shift work and education on cognitive performance at retirement was noted. Lower-educated shift workers performed better on cognitive tests than lower-educated day workers at retirement. Sensitivity analyses, however, indicated that the interactions appeared to be driven by selection effects. Lower-educated day workers demonstrated poorer cognitive ability in early adulthood than lower-educated shift workers, who may have selected jobs entailing higher cognitive demand. Conclusion There was no difference in late-life cognitive aging between individuals with a history of working shifts compared to those who had typical day work schedules during midlife.

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m 2 )], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population., (© 2017 American Society for Nutrition.)

In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences., Competing Interests: The authors declare no conflict of interest.

Background: Although research has shown that sleep disorders are prevalent among people with dementia, the temporal relationship is unclear. We investigated whether atypical sleep characteristics were associated with incident dementia while accounting for baseline cognitive functioning., Methods: Screening Across the Lifespan Twin (SALT) study participants were 11,247 individuals from the Swedish Twin Registry who were at least 65 years at baseline (1998-2002). Sleep and baseline cognitive functioning were assessed via the SALT telephone screening interview. Data on dementia diagnoses came from national health registers. Cox regression was performed to estimate hazard ratios for dementia., Results: After 17 years of follow-up, 1,850 dementia cases were identified. Short (≤6 hours) and extended (>9 hours) time in bed (TIB) compared to the middle reference group (hazard ratio = 1.40, 95% confidence interval = 1.06-1.85; hazard ratio = 1.11, 95% confidence interval = 1.00-1.24, respectively) and rising at 8:00 AM or later compared to earlier rising (hazard ratio = 1.12, 95% confidence interval = 1.01-1.24) were associated with higher dementia incidence. Bedtime, sleep quality, restorative sleep, and heavy snoring were not significant predictors. Findings stratified by baseline cognitive status indicated that the association between short TIB and dementia remained in those cognitively intact at the start., Conclusions: Short and extended TIB and delayed rising among older adults predicted increased dementia incidence in the following 17 years. The pattern of findings suggests that extended TIB and late rising represent prodromal features whereas short TIB appeared to be a risk factor for dementia., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve., Competing Interests: The authors declare that no competing interests exist.

The aims of the present study were to: (1) describe and compare individual characteristics of hospitalized and not hospitalized community living persons, and (2) to determine factors that are associated with hospitalization risk over time. We conducted a prospective study with a multifactorial approach based on the population-based longitudinal Swedish Adoption/Twin Study of Aging (SATSA). A total of 772 Swedes (mean age at baseline 69.7 years, range 46-103, 59.8% females) answered a postal questionnaire about physical and psychological health, personality and socioeconomic factors. During nine years of follow-up, information on hospitalizations and associated diagnoses were obtained from national registers. Results show that 484 persons (63%) had at least one hospital admission during the follow-up period. The most common causes of admission were cardiovascular diseases (25%) and tumors (22%). Cox proportional hazard regression models controlling for age, sex and dependency within twin pairs, showed that higher age (HR=1.02, p<0.001) and more support from relatives (HR=1.09, p=0.028) were associated with increased risk of hospitalization, while marital status (unmarried (HR=0.75, p=0.033) and widow/widower (HR=0.69, p<0.001)) and support from friends (HR=0.93, p=0.029) were associated with lower risk of hospitalization. Social factors were important for hospitalization risk even when medical factors were controlled for in the analyses. Number of diseases was not a risk in the final regression model. Hospitalization risk was also different for women and men and within different age groups. We believe that these results might be used in future interventions targeting health care utilization., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Both physical functioning and cognitive abilities are important for well-being, not least in old age. Grip strength is often considered an indicator of general vitality and, as such, may predict cognitive functioning. Few longitudinal studies have examined the relationship between grip strength and cognition, especially where specific cognitive abilities have been targeted., Method: Participants (n = 708, age range: 40-86 years at baseline) came from the population-based longitudinal Swedish Adoption/Twin Study of Aging. We used a longitudinal follow-up of 6 waves during 20 years. For the analyses, we used latent growth modeling, where latent growth trajectories were fitted to the cognitive traits (verbal ability, spatial ability, processing speed, and memory) or to the grip strength values and each, respectively, treated as time-varying covariates of the other trait., Results: Results supported a longitudinal influence of grip strength on changes in cognitive function. Grip strength performance was associated with change in the 4 cognitive abilities after age 65 years., Discussion: A rather stable connection was found between grip strength and cognitive abilities starting around 65 years of age. The starting period suggests that the association may be due to lifestyle changes, such as retirement, or to acceleration of the aging processes., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hospitalisation of nursing home residents might lead to deteriorating health., Aim: To evaluate physical and psychological factors associated with hospitalisation risk among nursing home residents., Design: Prospective study with three years of follow-up., Methods: Four hundred and twenty-nine Swedish nursing home residents, ages 65-101 years, from 11 nursing homes in three municipalities were followed during three years. The participants' physical and psychological status was assessed at baseline. A Cox proportional hazards model was used to evaluate factors associated with hospitalisation risk using STATA., Results: Of the 429 participants, 196 (45.7%) were hospitalised at least once during the three-year follow-up period, and 109 (25.4%) during the first six months of the study. The most common causes of hospitalisation were cardiovascular diseases or complications due to falls. A Cox regression model showed that residents who have had previous falls (P < 0.001), are malnourished (P < 0.001), use a greater number of drugs (P < 0.001) and have more diseases (P < 0.001), are at an increased risk of hospitalisation., Conclusion: Nursing home residents are frequently hospitalised, often due to falls or cardiovascular diseases. Study results underscore the relationships between malnutrition, previous falls, greater numbers of drugs and diseases and higher risk of hospitalisation., Implications for Practice: Preventive interventions aimed at malnutrition and falls at the nursing home could potentially reduce the number of hospitalisations. With improved education and support to nurses concerning risk assessment at the nursing homes, it may be possible to reduce the numbers of avoidable hospitalisation among nursing home residents and in the long run improve quality of life and reduce suffering., (© 2015 John Wiley & Sons Ltd.)

Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE., Competing Interests: Dr. Korhonen has served as a consultant on nicotine dependence for Pfizer (Finland) in 2011–2015.

The purpose of this study was to explore how older people experience and perceive decisions to seek hospital care while receiving home health care. Twenty-two Swedish older persons were interviewed about their experiences of decision to seek hospital while receiving home health care. The interviews were analyzed using qualitative content analysis. The findings consist of one interpretative theme describing an overall confidence in hospital staff to deliver both medical and psychosocial health care, In Hospital We Trust, with three underlying categories: Superior Health Care, People's Worries, and Biomedical Needs. Findings indicate a need for establishing confidence and ensuring sufficient qualifications, both medical and psychological, in home health care staff to meet the needs of older people. Understanding older peoples' arguments for seeking hospital care may have implications for how home care staff address individuals' perceived needs. Fulfillment of perceived health needs may reduce avoidable hospitalizations and consequently improve quality of life., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although evidence indicates that Type II Diabetes is related to abnormal brain aging, the influence of elevated blood glucose on long-term cognitive change is unclear. In addition, the relationship between diet-based glycemic load and cognitive aging has not been extensively studied. The focus of this study was to investigate the influence of diet-based glycemic load and blood glucose on cognitive aging in older adults followed for up to 16 years., Methods: Eight-hundred and thirty-eight cognitively healthy adults aged ≥50 years (M = 63.1, SD = 8.3) from the Swedish Adoption/Twin Study of Aging were studied. Mixed effects growth models were utilized to assess overall performance and change in general cognitive functioning, perceptual speed, memory, verbal ability, and spatial ability as a function of baseline blood glucose and diet-based glycemic load., Results: High blood glucose was related to poorer overall performance on perceptual speed as well as greater rates of decline in general cognitive ability, perceptual speed, verbal ability, and spatial ability. Diet-based glycemic load was related to poorer overall performance in perceptual speed and spatial ability., Conclusion: Diet-based glycemic load and, in particular, elevated blood glucose appear important for cognitive performance/cognitive aging. Blood glucose control (perhaps through low glycemic load diets) may be an important target in the detection and prevention of age-related cognitive decline., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Few studies have examined associations of multi-faceted demographic, health and lifestyle factors with long-term change in grip strength performance across the adult lifespan. The aim of this study was to examine the associations of risk factors in specific parts of the adult lifespan (e.g. in early midlife, in late midlife and in old adulthood) separately for women and men., Methods: Data came from the longitudinal Swedish Adoption/Twin Study of Aging (SATSA). Grip strength performance was followed in 849 participants who were 50-88 years of age at baseline. The follow-up period with seven waves of data of grip strength was 22 years, and the risk factors were measured up to 20 years before the assessment of grip strength. Latent growth modelling was used for the longitudinal analyses., Results: A gender difference in the type of factors associated with grip strength performance and development across the adult lifespan was found. Significant factors for the age slopes for women were stress, smoking and dementia. For men, marital status, mean arterial pressure, physical activity at work and having a chronic disorder were of importance. These factors varied in their associations with grip strength across the adult lifespan., Conclusion: Factors measured earlier in adulthood were associated with grip strength decline in late midlife and old adulthood. Gender-specific patterns of risk factors suggest that it may be worthwhile to conduct research on grip and muscle strength (and biological vitality) separately for men and women., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)