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We examined whether attained socioeconomic status (SES) moderated genetic and environmental sources of individual differences in cognitive performance using pooled data from 9 adult twin studies. Prior work concerning SES moderation of cognitive performance has focused on rearing SES. The current adult sample of 12,196 individuals (aged 27-98 years) allowed for the examination of common sources of individual differences between attained SES and cognitive performance (signaling potential gene-environment correlation mechanisms, rGE), as well as sources of individual differences unique to cognitive performance (signaling potential gene-environment interaction mechanisms, G × E). Attained SES moderated sources of individual differences in 4 cognitive domains, assessed via performance on 5 cognitive tests ranging 2,149 to 8,722 participants. Attained SES moderated common sources of influences for 3 domains and influences unique to cognition in all 4 domains. The net effect was that genetic influences on the common pathway tended to be relatively more important at the upper end of attained SES indicating possible active rGE, whereas, genetic influences for the unique pathway were proportionally stable or less important at the upper end of attained SES. As a noted exception, at the upper end of attained SES, genetic influences unique to perceptual speed were amplified and genetic influences on the common pathway were dampened. Accounting for rearing SES did not alter attained SES moderation effects on cognitive performance, suggesting mechanisms germane to adulthood. Our findings suggest the importance of gene--environment mechanisms through which attained SES moderates sources of individual differences in cognitive performance.

Antihypertensive, lipid‐lowering, and blood glucose‐lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow‐up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population‐based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self‐controlled analysis, where each individual is his/her own control, thereby adjusting for all time‐stable confounders. The analysis was additionally adjusted for time‐varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5–82.8 years at the first in‐person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid‐modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = −0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid‐modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes. [ABSTRACT FROM AUTHOR]

Objectives The educational gradient in late-life health is well established. Despite this, there are still ambiguities concerning the role of underlying confounding by genetic influences and gene-environment (GE) interplay. Here, we investigate the role of educational factors (attained and genetic propensities) on health and mortality in late life using genetic propensity for educational attainment (as measured by a genome-wide polygenic score, PGSEdu) and attained education. Methods By utilizing genetically informative twin data from the Swedish Twin Registry (n = 14,570), we investigated influences of the educational measures, familial confounding as well as the possible presence of passive GE correlation on both objective and subjective indicators of late-life health, that is, the Frailty Index, Multimorbidity, Self-rated health, cardiovascular disease, and all-cause mortality. Results Using between-within models to adjust for shared familial factors, we found that the relationship between educational level and health and mortality later in life persisted despite controlling for familial confounding. PGSEdu and attained education both uniquely predicted late-life health and mortality, even when mutually adjusted. Between-within models of PGSEdu on the health outcomes in dizygotic twins showed weak evidence for passive GE correlation (prGE) in the education-health relationship. Discussion Both genetic propensity to education and attained education are (partly) independently associated with health in late life. These results lend further support for a causal education-health relationship but also raise the importance of genetic contributions and GE interplay. [ABSTRACT FROM AUTHOR]

Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying multivariate growth curve models to longitudinal data from 857 individuals from the Swedish Adoption/Twin Study of Aging, who had been measured on 11 cognitive variables representative of verbal, spatial, memory, and processing speed abilities up to 5 times over up to 16 years between ages 50 and 96 years. Between ages 50 and 65 years scores on different tests changed relatively independently of one another, and there was little evidence for strong underlying dimensions of change. In contrast, over the period between 65 and 96 years of age, there were strong interrelations among rates of change both within and across domains. During this age period, variability in rates of change were, on average, 52% domain-general, 8% domain-specific, and 39% test-specific. Quantitative genetic decomposition indicated that 29% of individual differences in a global domain-general dimension of cognitive changes during this age period were attributable to genetic influences, but some domain-specific genetic influences were also evident, even after accounting for domain-general contributions. These findings are consistent with a balanced global and domain-specific account of the genetics of cognitive aging.

To evaluate temporal dynamics between loneliness and both objective and subjective health (i.e. functional impairment and self-rated health) in mid- to late-adulthood. We applied bivariate dual-change-score models to longitudinal data from 3 Swedish twin studies (N = 1,939) to explore dynamic associations between loneliness and health across 3 age ranges (50–69, 70–81, and 82+ years) to investigate whether associations between loneliness and health change with age due to increasing incidence of chronic health conditions and bereavement. Results showed bidirectional associations between loneliness and both objective and subjective health, with adverse impacts of loneliness observed on subsequent subjective and objective health beginning at age 70. Associations between health and subsequent loneliness were observed after age 82 and varied for subjective and objective health, with subjective health associated with less loneliness and objective health associated with greater loneliness. Our results indicate dynamic associations between loneliness and health with age in mid- to late-adulthood, with earlier impacts of loneliness on health and later impacts of health on loneliness that vary for objective and subjective measures of health. These findings suggest impacts of health on loneliness may arise later in life when worsening health or mobility interfere with social interaction. [ABSTRACT FROM AUTHOR]

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories for processing speed and cognitive abilities. Longitudinal twin data from the Swedish Adoption/Twin Study of Aging, including up to 5 measurement occasions covering a 16-year period, were available from 806 participants ranging in age from 50 to 88 years at the 1st measurement wave. Factors were generated to tap 4 cognitive domains: verbal ability, spatial ability, memory, and processing speed. Model-fitting indicated that genetic variance for processing speed was a leading indicator of variation in age changes for spatial and memory ability, providing additional support for processing speed theories of cognitive aging. (Contains 6 figures, 7 tables, and 1 footnote.)

Sex differences in the etiology of normal cognitive functioning in aging remain largely unexplored. We conducted an investigation of genetic and environmental contributions to sex differences in level of cognitive performance and rate of decline in the Swedish Adoption/Twin Study of Aging (SATSA) (Finkel & Pedersen, 2004) data set. Behavioral genetic parameterizations of a latent growth curve model were fit to longitudinal data on 11 cognitive measures. Seven hundred and ninety-eight non-demented individuals had cognitive data across four waves of measurement covering 13 years. Participants ranged in age from 44 to 88 at first testing wave; 60% were female. Results indicated sex differences in mean performance for five cognitive measures and in rates of decline for Information and Card Rotations. Only Synonyms demonstrated sex differences in genetic and environmental contributions to mean performance: heritability was higher in men than women. Despite differential longevity and susceptibility to disease, there are no consistent indications that men and women show different patterns of cognitive aging.

To develop recommendations for tree selection in Continuous Cover Forestry (CCF), access to valid tools for simulating growth at individual tree-level is necessary. To assist efforts to develop such tools, in this study, long-term observation data from two uneven-sized Norway spruce plots in southern Sweden are used to evaluate old and new individual-tree growth models (two established Swedish models, two new preliminary models and included as a reference, a Finnish model). The plots' historical management records and site conditions are the same, but their last thinning treatment differs. Observed diameter increment at tree-level is investigated in relation to treatment. Individual tree growth residuals of tested models are evaluated in relation to tree diameter, treatment, projection length and sensitivity to the predictor mean stand age. Furthermore, the relations between displayed residuals and basal area local competition are analysed. The analyses indicate that active thinning made annual diameter increment independent of tree diameter above a threshold level, while the absence of thinning supported a concave relationship. All tested models displayed a significant linear bias leading to overestimation of small trees' growth and increasing underestimations of larger trees' growth with tree diameter. All distance-independent models displayed residual trends related to local competition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper characterizes the value of biodiversity and ecosystem resilience by formalizing a stochastic dynamic bioeconomic model of pollinator diversity under climate changes, with an application to oil rapeseed production in the Stockholm region of Sweden. It studies the optimal provision of semi-natural habitat for two different pollinator bee species: bumble bees and solitary wild bees. It is found that, despite being less effective, solitary bees hold considerable resilience value due to the differences in how the two species respond to temperature shocks. The paper also discusses the role of spatial aspects, in particular the reduced pollination effectiveness due to spatially uneven allocation of semi-natural habitats. It is found that spatial unevenness leads to an increase in the habitat provision, with an attendant reduction in the resilience value of solitary bees. [ABSTRACT FROM AUTHOR]

Background: While sex differences in incidence of Alzheimer's disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD.Objective: We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia.Methods: Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,740 individual twins with measured ɛ4 alleles. Dementia diagnoses were based on clinical workup and national health registry linkage.Results: Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOEɛ4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2-5 years following the first twin's diagnosis.Conclusion: For All Dementia, AD Only, and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated. [ABSTRACT FROM AUTHOR]

Although previous studies examining leukocyte telomere length (LTL) and all-cause mortality controlled for several confounders, the observed association could be biased due to unmeasured confounders, including familial factors. We aimed to examine the association of LTL with all-cause mortality in a Swedish twin sample while adjusting for familial factors and allowing for time-dependent effects. A total of 366 participants (174 twin pairs and 18 individuals) were recruited from the Swedish Twin Registry. LTL was assessed using the Southern blot method. All-cause mortality data were obtained through linkage with the Swedish Population Registry, updated through November 15, 2017. To control for familial factors within twin pairs, we applied a between-within shared frailty model based on generalized survival models. Overall, 115 (31.4%) participants were men and 251 (68.6%) were women. The average age of the study participants when blood was drawn was 79.1 years, and follow-up duration ranged from 10 days to 25.7 years (mean = 10.2 years). During the follow-up period, 341 (93.2%) participants died. Shorter LTL was associated with higher mortality rates when controlling for familial factors in the between-within shared frailty model. We found significant time-dependent effects of LTL on all-cause mortality, where the mortality rate ratios were attenuated with increasing age. [ABSTRACT FROM AUTHOR]

Cognitive decline and anxiety symptoms commonly co-occur in later life, but the temporal order of changes on these two attributes is unclear. Specifically, it is unknown if greater anxiety leads to subsequent declines in cognitive performance or if worse cognitive performance leads to increased anxiety. In this study, we sought to elucidate the temporal dynamics between anxiety symptoms and cognitive performance across old age-that is, the extent to which level and change in one variable influence subsequent changes in a second variable. We examined data from 721 nondemented participants from the Swedish Adoption/Twin Study of Aging. Participants completed as many as eight assessments of cognitive performance and anxiety over a 26-year period. Bivariate dual-change score models were fit to examine the dynamic association between anxiety and cognitive performance. Bidirectional associations between anxiety and cognitive performance were found among measures of processing speed, attention, and memory but not visuospatial abilities. Higher anxiety was associated with greater declines in processing speed over the duration of 6 years and worsening attention over a span of 3 years. The reverse direction was also significant in that slower processing speed, worse attention, and poorer nonverbal and working memory performance were associated with larger increases in anxiety 3 years later. These findings highlight that in cognitively intact older adults, the association between anxiety and worse cognitive performance is bidirectional and complex. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

Swedish climate policy targets net zero greenhouse gases (GHG) by mid-century, with road transport independent of fossil fuels by 2030, requiring far-reaching changes in the way energy is used. Forest management is expected to support carbon sequestration and provide biomass for various uses, including energy. In this paper, we combine two energy scenarios with four forest scenarios and quantify GHG balances associated with energy-use for heat, electricity, and road transport, and with forest management and production, use, and end-of-life management of various forest products, including products for export. The aggregated GHG balances are evaluated in relation to the 2-degree target and an allocated Swedish CO 2 budget. The production of biofuels in the agriculture sector is considered but not analyzed in detail. The results suggest that Swedish forestry can make an important contribution by supplying forest fuels and other products while maintaining or enhancing carbon storage in vegetation, soils, and forest products. The GHG neutrality goal is not met in any of the scenarios without factoring in carbon sequestration. Measures to enhance forest productivity can increase output of forest products (including biofuels for export) and also enhance carbon sequestration. The Swedish forest sector can let Sweden reach net negative emissions, and avoid “using up” its allocated CO 2 budget, thereby increasing the associated emissions space for the rest of the world. [ABSTRACT FROM AUTHOR]

Using a unique and highly detailed data set on energy consumption at the appliance-level for 200 Swedish households, seemingly unrelated regression (SUR)-based end-use specific load curves are estimated. The estimated load curves are then used to explore possible restrictions on load shifting (e.g. the office hours schedule) as well as the cost implications of different load shift patterns. The cost implications of shifting load from "expensive" to "cheap" hours, using the Nord pool spot prices as a proxy for a dynamic price, are computed to be very small; roughly 2-4% reduction in total daily cost from shifting load up to five hours ahead, indicating small incentives for households (and retailers) to adopt dynamic pricing of electricity. [ABSTRACT FROM AUTHOR]

Background: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and/or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample.Methods: We analysed data from three genetically informative samples containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured differed between the samples. We used three methods of genetic analysis to examine the relationship between intelligence and lifespan: we calculated the proportion of the more intelligent twins who outlived their co-twin; we regressed within-twin-pair lifespan differences on within-twin-pair intelligence differences; and we used the resulting regression coefficients to model the additive genetic covariance. We conducted a meta-analysis of the regression coefficients across the three samples.Results: The combined (and all three individual samples) showed a small positive phenotypic correlation between intelligence and lifespan. In the combined sample observed r = .12 (95% confidence interval .06 to .18). The additive genetic covariance model supported a genetic relationship between intelligence and lifespan. In the combined sample the genetic contribution to the covariance was 95%; in the US study, 84%; in the Swedish study, 86%, and in the Danish study, 85%.Conclusions: The finding of common genetic effects between lifespan and intelligence has important implications for public health, and for those interested in the genetics of intelligence, lifespan or inequalities in health outcomes including lifespan. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Abstract: We quantify the potential effects of intensive forest management activities on forest production in north-central Sweden over the next 100 years, and calculate the potential climate change mitigation feedback effect due to the resulting increased carbon stock and increased use of forest products. We analyze and compare four different forest management scenarios (Reference, Environment, Production, and Maximum), all of which include the expected effects of climate change based on SRES B2 scenario. Forest management practices are intensified in Production scenario, and further intensified in Maximum scenario. Four different models, BIOMASS, HUGIN, Q-model, and Substitution model, were used to quantify net primary production, forest production and harvest potential, soil carbon, and biomass substitution of fossil fuels and non-wood materials, respectively. After integrating the models, our results show that intensive forestry may increase forest production by up to 26% and annual harvest by up to 19%, compared to the Reference scenario. The greatest single effect on the carbon balance is from using increased biomass production to substitute for fossil fuels and energy intensive materials. Carbon stocks in living tree biomass, forest soil and wood products also increase. In total, a net carbon emission reduction of up to 132Tg (for Maximum scenario) is possible during the next 100 years due to intensive forest management in two Swedish counties, Jämtland and Västernorrland. [Copyright &y& Elsevier]

Abstract: In this study we estimate the effects of climate change on forest production in north-central Sweden, as well as the potential climate change mitigation feedback effects of the resulting increased carbon stock and forest product use. Our results show that an average regional temperature rise of 4 °C over the next 100 years may increase annual forest production by 33% and potential annual harvest by 32%, compared to a reference case without climate change. This increased biomass production, if used to substitute fossil fuels and energy-intensive materials, can result in a significant net carbon emission reduction. We find that carbon stock in forest biomass, forest soils, and wood products also increase, but this effect is less significant than biomass substitution. A total net reduction in carbon emissions of up to 104 Tg of carbon can occur over 100 years, depending on harvest level and reference fossil fuel. [Copyright &y& Elsevier]

The possibility of genotype-environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype-nonshared environment interactions. Multiple 'variability genes' were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to 'contextualize' the possible nonshared environmental influences for found gene-environment (G x E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G x E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors. [ABSTRACT FROM AUTHOR]

Petterson et al., identified 16,983 Swedish men from the Swedish Hospital Discharge Register who underwent orchidopexy for undescended testis, between 1964 to 1999. As almost all patients in Sweden are treated at public hospitals, this data was fairly comprehensive. Subjects who underwent orchidopexy before the age of 20 years were included. Two hundred and five men who emigrated from Sweden after surgery but did not immigrate back before the start of their follow-up and one who had testicular cancer at the time of beginning the study were excluded. Other exclusion includes those with ambiguity on information on date of orchiodopexy or sex. The subjects were followed from 15 years of age or the age of orchidopexy plus one year, whichever occurred earlier, till the date of diagnosis of testicular cancer, upper age limit of 55 years, emigration, death, or December 2000. The authors have calculated the expected period-specific incidence for five-year age periods, based on the incidence in the Swedish general population. Based on the observed number of cases in the study population, the relative risk was estimated. They used a number of covariate analyses, including separation of the follow-up into three distinct calendar periods, time of orchidopexy and the place where orchidopexy was performed. Further statistical analysis using Schoenfeld residuals indicated that the assumption of hazard ratio was correct, and all such confounders were eliminated. The mean follow-up was 12.4 years. Mean age at orchidopexy was 8.6 years. Though only 20 cases was expected in the study group based on the incidence in the general population, 56 were documented. The standardized incidence ratio of testicular cancer in those undergoing orchidopexy before the age of 13 years was 2.23, as opposed to those above the age of 13 years, where it was almost double at 5.40. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials, and no patients with a pathological response have relapsed after a median follow up of 32 months. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo trial was to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective.Methods: OpACIN-neo is a multicentre, open-label, phase 2, randomised, controlled trial. Eligible patients were aged at least 18 years, had a WHO performance status of 0-1, had resectable stage III melanoma involving lymph nodes only, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients were enrolled from three medical centres in Australia, Sweden, and the Netherlands, and were randomly assigned (1:1:1), stratified by site, to one of three neoadjuvant dosing schedules: group A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks intravenously; group B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks intravenously; or group C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3 mg/kg once every 2 weeks intravenously. The investigators, site staff, and patients were aware of the treatment assignment during the study participation. Pathologists were masked to treatment allocation and all other data. The primary endpoints were the proportion of patients with grade 3-4 immune-related toxicity within the first 12 weeks and the proportion of patients achieving a radiological objective response and pathological response at 6 weeks. Analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02977052, and is ongoing with an additional extension cohort and to complete survival analysis.Findings: Between Nov 24, 2016 and June 28, 2018, 105 patients were screened for eligibility, of whom 89 (85%) eligible patients were enrolled and randomly assigned to one of the three groups. Three patients were excluded after randomisation because they were found to be ineligible, and 86 received at least one dose of study drug; 30 patients in group A, 30 in group B, and 26 in group C (accrual to this group was closed early upon advice of the Data Safety Monitoring Board on June 4, 2018 because of severe adverse events). Within the first 12 weeks, grade 3-4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. The difference in grade 3-4 toxicity between group B and A was -20% (95% CI -46 to 6; p=0·158) and between group C and group A was 10% (-20 to 40; p=0·591). The most common grade 3-4 adverse events were elevated liver enzymes in group A (six [20%)]) and colitis in group C (five [19%]); in group B, none of the grade 3-4 adverse events were seen in more than one patient. One patient (in group A) died 9·5 months after the start of treatment due to the consequences of late-onset immune-related encephalitis, which was possibly treatment-related. 19 (63% [95% CI 44-80]) of 30 patients in group A, 17 (57% [37-75]) of 30 in group B, and nine (35% [17-56]) of 26 in group C achieved a radiological objective response, while pathological responses occurred in 24 (80% [61-92]) patients in group A, 23 (77% [58-90]) in group B, and 17 (65% [44-83]) in group C.Interpretation: OpACIN-neo identified a tolerable neoadjuvant dosing schedule (group B: two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg) that induces a pathological response in a high proportion of patients and might be suitable for broader clinical use. When more mature data confirm these early observations, this schedule should be tested in randomised phase 3 studies versus adjuvant therapies, which are the current standard-of-care systemic therapy for patients with stage III melanoma.Funding: Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]