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Purpose: To examine age‐related macular degeneration (AMD) and retinal pigment epithelium (RPE)–Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. Methods: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35‐degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age‐Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE‐BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. Results: Twenty‐nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2–4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3–4) versus the other being unaffected (AREDS 1). The within‐pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418–0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE‐BrM complex volume. RPE‐BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172–0.688, p < 0.01). Conclusion: A substantial proportion of monozygotic twin pairs are discordant with regard to age‐related macular degeneration phenotype. RPE‐BrM complex volume associated with age and intermediate and late AMD. [ABSTRACT FROM AUTHOR]

Aim: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole‐body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. Methods: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co‐twins 7.6 kg/m2; eight female pairs). Ten pairs completed the 6‐month long training intervention. We measured lumbar vertebral and femoral BM insulin‐stimulated glucose uptake (GU) using 18F‐FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. Results: At baseline, heavier co‐twins had higher lumbar vertebral BM GU (p <.001) and lower bone turnover markers (all p <.01) compared with leaner co‐twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole‐body insulin sensitivity, aerobic capacity (both p <.05) and femoral BM GU (p =.008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p =.02), as GU tended to decrease in heavier co‐twins (p =.06) while there was no change in leaner co‐twins. Conclusions: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co‐twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity. [ABSTRACT FROM AUTHOR]

Background: The association of sleep bruxism with mortality has not been studied. Objectives: Altogether 12 040 subjects from the nationwide Finnish twin cohort were included in the analyses. We examined whether self‐reported sleep bruxism is associated with increased risk of mortality, and if so, whether the effect is independent of known common risk factors. The time span of the follow‐up was 30 years. Methods: Cox proportional hazards regression models (Hazard Ratios and their 95% Confidence Intervals) adjusted by age, sex and covariates were used to assess the effect of baseline bruxism status in 1990 on future mortality in 1990–2020. Results: The risk of mortality among all participants (n = 12 040), independent of missing covariates and adjusted by age and sex, was 40% higher in weekly bruxers than in never bruxers (HR 1.40, 95% CI 1.16–1.68, p <.001). However, when adjusted by all studied covariates, (n = 11 427) the risk was no longer observed (HR 1.04, 95% CI 0.86–1.25, p =.717). Despite the overall lack of between bruxism and mortality after adjustment for covariates, we examined the cause‐specific risks for major cause‐of‐death groups. There were no substantial associations of weekly bruxism with major disease outcomes by the fully adjusted hazard ratios for them. Conclusion: Bruxism does not kill—in line with its definition of being rather a behaviour (with all its phenotypes) than a disease. [ABSTRACT FROM AUTHOR]

Background: Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self‐reported sleep bruxism was correlated longitudinally, pairwise and cross‐twin over a 20‐year period. Objectives: Self‐reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same‐sex twins born 1945–1957. Methods: We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross‐sectional zygosity correlations and the zygosity‐specific cross‐twin cross‐time correlations. Results: Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross‐twin cross‐time correlations were higher in MZ twins than in DZ twins, but less than the cross‐sectional MZ and DZ pairwise correlations. Conclusions: The higher correlation of reported sleep bruxism in the cross‐twin cross‐time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women. [ABSTRACT FROM AUTHOR]

Objective: This study investigated 36‐year BMI trajectories in twins whose BMI in young adulthood was below, within, or above their genetically predicted BMI, with a focus on twin pairs with large intrapair BMI differences (within‐pair ΔBMI ≥ 3 kg/m2). Methods: Together, 3227 like‐sexed twin pairs (34% monozygotic) were examined at age ~30 years in 1975 and followed up in 1981, 1990, and 2011. An individual's observed BMI in 1975 was considered within (±2.0), below (<−2.0), or above (>+2.0) genetically predicted BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms. Results: In monozygotic and dizygotic twin pairs with large intrapair BMI differences, the co‐twin with a higher observed BMI in 1975 deviated above predicted BMI more frequently (~2/3) than the co‐twin with a lower BMI deviated below prediction (~1/3). Individuals below, within, and above prediction in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% CI: 4.3–4.8). Conclusions: Categorizing BMI as below, within, or above polygenic risk score‐predicted BMI helps identifying individuals who have been resistant or susceptible to weight gain. This may provide new insights into determinants and consequences of obesity. [ABSTRACT FROM AUTHOR]

Summary: Background: Living in single parent and blended families or as an only child—compared to living in two‐parent biological families or with siblings, respectively—is associated with a higher body mass index (BMI) in cross‐sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health. Objectives: This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS). Methods: Cross‐sectional data from 7804 children participating in the European multi‐center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007–2010) were used. Family structure was assessed by a detailed interview. BMI z‐score and the MetS were based on measured anthropometry, blood pressure, high‐density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS. Results: Children from single‐parent families had higher BMI z‐scores in the cross‐sectional (β = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two‐parent families. Cross‐sectionally, the number of siblings was associated with lower BMI z‐scores (β = −0.07, 95% CI: −0.10 to −0.03) and lower MetS (β = −0.14, 95% CI: −0.26 to −0.01). Longitudinally, only children between baseline and follow‐up had higher BMI z‐scores at follow‐up (β = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings. Conclusion: Obesity prevention measures should focus on single‐parent households and families with an only child. [ABSTRACT FROM AUTHOR]

Background: Obesity is a heritable complex phenotype that can increase the risk of age‐related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives: We aimed to assess the cross‐sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results: Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p‐value = 6.1 × 10–12) per one‐unit BMI increase. Additionally, heavier twins in a BMI‐discordant MZ twin pair (ΔBMI >3 kg/m2) had an epigenetic age 5.2 months older than their lighter cotwin (p‐value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta‐analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p‐value = 4.1 × 10–25) from adjusted models. Conclusion: We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance. [ABSTRACT FROM AUTHOR]

Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure‐time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long‐term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long‐term LTPA discordant MZ twin pairs have participated in multi‐dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long‐term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high‐density lipoprotein particles. The findings increase our understanding on the possible site‐specific and system‐level effects of long‐term LTPA. [ABSTRACT FROM AUTHOR]

Maintenance of vigorous exercise habits from young to old age is considered protective against hip fractures, but data on fracture risk in lifelong vigorous exercisers are lacking. This longitudinal cohort study examined the hazard of hip fractures in 1844 male former athletes and 1216 population controls and in relation to exercise volume and intensity in later years. Incident hip fractures after age 50 years were identified from hospital discharge register from 1972 to 2015. Exercise and covariate information was obtained from questionnaires administered in 1985, 1995, 2001, and 2008. Analyses were conducted using extended proportional hazards regression model for time‐dependent exposures and effects. During the mean ± SD follow‐up of 21.6 ± 10.3 years, 62 (3.4%) athletes and 38 (3.1%) controls sustained a hip fracture. Adjusted hazard ratio (HR) indicated no statistically significant difference between athletes and controls (0.84; 95% confidence interval [CI], 0.55–1.29). In subgroup analyses, adjusted HRs for athletes with recent high (≥15 metabolic equivalent hours [MET‐h]/week) and low (<15 MET‐h/week) exercise volume were 0.83 (95% CI, 0.46–1.48) and 1.04 (95% CI, 0.57–1.87), respectively, compared with controls. The adjusted HR was not statistically significant between athletes with low‐intensity exercise (<6 METs) and controls (1.08; 95% CI, 0.62–1.85). Athletes engaging in vigorous‐intensity exercise (≥6 METs at least 75 minutes/week) had initially 77% lower hazard rate (adjusted HR 0.23; 95% CI, 0.06–0.86) than controls. However, the HR was time‐dependent (adjusted HR 1.04; 95% CI, 1.01–1.07); by age 75 years the HRs for the athletes with vigorous‐intensity exercise reached the level of the controls, but after 85 years the HRs for these athletes increased approximately 1.3‐fold annually relative to the controls. In conclusion, these data suggest that continuation of vigorous‐intensity exercise is associated with lower HR of hip fracture up to old age. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: Do drinking patterns in late adolescence/early adulthood predict lifetime childlessness and number of children? Research on this question has been only tangentially relevant and the results inconsistent. The designs used to date have been compromised by genetic and environmental confounds that are poorly controlled; covariate effects of smoking and education that are often ignored; males being understudied; population‐based sampling rare, and long‐term prospective studies with genetically informative designs yet to be reported. Method: In a 33‐year follow‐up, we linked the drinking patterns of >3500 Finnish twin pairs, assessed at ages 18–25, to registry data on their eventual number of children. Analyses distinguished associations of early drinking patterns with lifetime childlessness from those predictive of family size. Within‐twin pair analyses used fixed‐effects regression models to account for shared familial confounds and genetic liabilities. Childlessness was analyzed with Cox proportional hazards models and family size with Poisson regression. Analyses within‐pairs and of twins as individuals were run before and after adjustment for smoking and education, and for oral contraceptive (OC) use in individual‐level analyses of female twins. Results: Baseline abstinence and heavier drinking both significantly predicted lifetime childlessness in individual‐level analyses. Few abstinent women used OCs, but they were nonetheless more often eventually childless; adjusting for smoking and education did not affect this finding. Excluding childless twins, Poisson models of family size showed heavier drinking at 18–25 to be predictive of fewer children in both men and women. Those associations were replicated in within‐pair analyses of dizygotic twins, each level of heavier drinking being associated with smaller families. Among monozygotic twins, associations of drinking with completed family size yielded effects of similar magnitude, reaching significance at the highest levels of consumption, ruling out familial confounds. Conclusions: Compared to moderate levels of drinking, both abstinence and heavier drinking in late adolescence/early adulthood predicted a greater likelihood of lifetime childlessness and eventual number of children. Familial confounds do not fully explain these associations. [ABSTRACT FROM AUTHOR]

The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow‐up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow‐up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co‐twin was diagnosed with any of the following tobacco‐related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co‐twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair‐specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco‐related cancer sites, we recorded 7379 cases during median 27 years of follow‐up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17‐1.48) and current (HR 2.14 [1.95‐2.34]) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15‐2.98) among current smokers and 1.69 (1.00‐2.87) among former smokers when compared to their never smoking co‐twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers. [ABSTRACT FROM AUTHOR]

The article discusses research which found that smoking cessation is not associated with a decline in reported sleep bruxism in middle-aged Finnish twins. The study considered the role of environmental factors in the aetiology of sleep bruxism. It used Chi-square test to analyze the bruxism status of Finnish twins in 2011 and whether smoking cessation during 1990-2011 was associated with it.

Background: Most studies on the association between educational attainment and dementia have been conducted in unrelated individuals. Dementia‐discordant twin pairs can inform if the protective effect of education on dementia is evident when controlling for environmental and genetic effects. We investigated the association of educational attainment on all‐cause dementia, vascular dementia (VaD), and Alzheimer's disease (AD) mortality in a population‐based sample of dizygotic (DZ) and monozygotic (MZ) pairs. Method: Participants were from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975 (N = 29,784; mean age = 36.9±14.9years). Education was coded as <12 years versus ≥12 years. Registry‐based cause of death data until year 2020 was based on the International Classification of Diseases. We ran individual‐level cox proportional hazard models with sex as a covariate and conditional within‐twin‐pair models for education predicting all‐cause dementia, VaD, and AD mortality. We report hazard ratios (HR) with 95% confidence intervals (CI). Result: In individual‐level analyses higher education was associated with a decreased risk of all‐cause dementia (HR =.935, 95%CI =.934;.936, p<.001) and VaD (HR =.638, 95%CI =.637;.640, p<.001), but with an increased risk of AD (HR = 1.276, 95%CI = 1.275;1.277, p<.001). In co‐twin analyses of discordant DZ and MZ twin pairs, co‐twins with higher education had lower – although non‐significant – risk of all‐cause dementia (N = 52, HR =.688, 95%CI =.319;1.481, p =.339) or AD (N = 36, HR =.600, 95%CI:.218;1.651, p =.323). Co‐twin analyses were not done for VaD due to small number of discordant pairs (N = 6). Conclusion: This large population‐based sample showed that higher education is related to lower risk of all‐cause dementia and VaD mortality. Unexpectedly, higher education was related to higher AD mortality, but discordant twin pair analyses were informative regarding this counterintuitive result. This case‐control design, controlling for genetic and environmental effects, did not support any causality from higher education to higher AD risk. Despite the large sample, twin pairs – especially MZ twins – discordant for dementia are rare. Meta‐ or mega‐analysis of multiple large twin studies is needed to clarify if secondary education is related to lower risk of dementia, VaD, and AD mortality when controlling for genetic effects. [ABSTRACT FROM AUTHOR]

Objective: We assessed the detection, treatment and outcomes of DSM‐5 eating disorders in a nationwide community setting. Method: The FinnTwin12 cohort comprises twins born in 1983–1987 in Finland (n = 5,600), with follow‐up starting at age 12. We outline treatment and outcomes of the 127 females and 15 males diagnosed with a lifetime DSM‐5 eating disorder in interviews conducted for a subsample (n = 1,347) in their early 20s. Results: Only 45 (32%) of those diagnosed with eating disorder in the interviews had their condition detected in healthcare, and even fewer received treatment (30% of females, 13% of males). Anorexia nervosa (AN), bulimia nervosa, and atypical AN were detected and treated more often than other eating disorders. Five years after disease onset, 41% of those diagnosed had recovered. There were no statistically significant differences in the course of different eating disorders (log‐rank p = 0.66) but the outcome was more favourable among males (log‐rank p = 0.008). The likelihood of 5‐year recovery did not differ between those who had and who had not received treatment (41.1% vs. 40.5%, log‐rank p = 0.66). Conclusion: Although eating disorders are common and symptoms are persistent for many, they remain under‐diagnosed and under‐treated. In real‐world settings, effectiveness of provided treatments may be limited. Key points: Although eating disorders affected one in six females and one in 40 males in the community, only one‐third of these cases were detected by healthcare providers, and even fewer received any treatment. Atypical disorders remain rarely recognized and treated.Eating disorder symptoms can be persistent for many sufferers; 5 years after disease onset, less than two‐fifths of the females and two‐thirds of the males had recovered.Real‐world treatments available in healthcare may have limited effectiveness, as the likelihood of recovery within 5 years was 40 percent in both treated and untreated groups. [ABSTRACT FROM AUTHOR]

Background: We have established NONAGINTA – Memory and Health in 90‐year‐olds –study in a population‐based sample with 45 years of follow‐up. Our study is aimed to understand both, the antecedents of cognitive impairment and successful cognitive aging in the oldest‐old (90 years or older). Method: Participants were nonagenarians from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975. Ongoing 90‐year‐old data collection included postal questionnaire and telephone administered cognitive testing. Episodic memory (EM) was measured with total words recalled in three trials of 10‐word list. Predictors of EM included cognitive, health‐related, and psychological factors. Self‐reported educational attainment, body mass index (BMI), physical activity (METhours/day), life satisfaction and neuroticism were measured in middle age (N = 55, age M = 46.2, SD = 1.7 years) and in old age (N = 59‐67, age M = 91.3, SD = 1.9 years). Semantic verbal fluency (number of animals in 1‐minute) and depressive symptoms (Center for Epidemiological Studies – Depression (CES‐D)) were measured only in old age. We used individual level linear regression models with age and sex as covariates and adjusted for family structure. Result: To date, 67 individuals have cognitive data. On average, women (N = 36, M = 11.97, SD = 4.70) had better EM than men (N = 31, M = 11.10, SD = 4.74), but this difference was not statistically significant (p = 0.49). Better verbal fluency was significantly related to better EM (r = 0.34, p<0.001). Compared to those with 6 years of education, those with 7‐11 years and those with 12 or more years of education had significantly better EM: 4.03 (95%CI: 1.27‐6.80) (p = 0.005) and 5.75 (95%CI: 3.75‐7.45) (p<0.001) words more, respectively. Mean CES‐D was 12.3 (SD = 8.7) and 16% scored above the cut‐off for clinically significant depressive symptoms, however, depressive symptoms were not related to EM (p = 0.15). Middle age or old age BMI, physical activity, life satisfaction or neuroticism were not significantly related to EM (p's >0.32). Conclusion: Our preliminary results suggest that cognitive, but not midlife or old age physical or psychological health‐related factors, are associated with episodic memory performance in nonagenarians. Good episodic memory goes hand in hand with good semantic fluency and cognitive benefits of early life educational attainment are still evident in nonagenarians. [ABSTRACT FROM AUTHOR]

Background: Several risk and protective factors of dementia are known, but the importance of genetic and environmental influences and the antecedents of cognitive functioning in 90‐year‐olds are not well known. Genetic and environmental confounding can be controlled better by using family data compared to samples of unrelated individuals. We examined dementia risk factors in 90‐year‐olds by conducting a case‐control co‐twin study on the associations of physical and psychological well‐being with episodic memory (EM). Method: We invited 90‐year‐old twins from a population‐based older Finnish Twin Cohort study to participate in the ongoing NONAGINTA –study that includes questionnaires (risk factors) and telephone interview (cognitive functioning). To date, eight full same‐sex pairs have cognitive data available (6 female, 6 monozygotic). We calculated a risk score for each twin and co‐twin, based on the following factors: depressive symptoms (measured with the Center for Epidemiological Studies – Depression, CES‐D), body mass index (BMI), physical activity (MET hours), life satisfaction, neuroticism, and years of education. Within each twin pair, co‐twins were assigned as having greater versus lower risk score. We ran a paired t‐test to compare EM performance (total number of recalled words in three trials of 10‐word list) in co‐twins with greater versus lower risk score. Associations of individual factors with EM were studied with exact McNemar test. Result: Mean difference in EM within twin pairs was 3.38 (SD = 2.50). Pairwise correlation of EM was r = 0.75 and seven twin pairs were discordant for EM. Co‐twins with lower risk score remembered more words (M = 13.25, SD = 5.59) than their co‐twins with greater risk score (M = 12.88, SD = 5.82), but this difference was not significant (p = 0.82). Examining each risk factor individually, the strongest – non‐significant – association was that co‐twins with greater life satisfaction had better EM in 5/6 pairs (p = 0.10). Conclusion: Preliminary data did not indicate any significant within‐twin pair associations of dementia risk and episodic memory. As expected, co‐twins were highly similar in EM. Ongoing data collection will result in more twin pairs and greater statistical power to see if the suggestive association of greater life satisfaction (or other factors) with better EM is evident in nonagenarians. [ABSTRACT FROM AUTHOR]

Background and Aims Design Participants/Setting Measurements Findings Conclusions Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders.A random effects model accounting for nesting in families was used to control for measured confounders. Next, co‐twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co‐twins.Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland.Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use.Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co‐twin control [freq: stnd beta = −0.12, 95% confidence interval (CI) = −0.234, −0.013] and MZ only co‐twin control models (freq: stnd beta = −0.305, 95% CI = –0.523, −0.087; intox: stnd beta = −0.301, 95% CI = ‐0.528, −0.074).In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores. [ABSTRACT FROM AUTHOR]

Background Translocation of lipopolysaccharide from gram-negative bacteria into the systemic circulation results in endotoxemia. In addition to acute infections, endotoxemia is detected in cardiometabolic disorders, such as cardiovascular diseases and obesity. Methods and Results We performed a genome-wide association study of serum lipopolysaccharide activity in 11 296 individuals from 6 different Finnish study cohorts. Endotoxemia was measured by limulus amebocyte lysate assay in the whole population and by 2 other techniques (Endolisa and high-performance liquid chromatography/tandem mass spectrometry) in subpopulations. The associations of the composed genetic risk score of endotoxemia and thrombosis-related clinical end points for 195 170 participants were analyzed in FinnGen. Lipopolysaccharide activity had a genome-wide significant association with 741 single-nucleotide polymorphisms in 5 independent loci, which were mainly located at genes affecting the contact activation of the coagulation cascade and lipoprotein metabolism and explained 1.5% to 9.2% of the variability in lipopolysaccharide activity levels. The closest genes included KNG1 , KLKB1 , F12 , SLC34A1 , YPEL4 , CLP1 , ZDHHC5 , SERPING1 , CBX5 , and LIPC . The genetic risk score of endotoxemia was associated with deep vein thrombosis, pulmonary embolism, pulmonary heart disease, and venous thromboembolism. Conclusions The biological activity of lipopolysaccharide in the circulation (ie, endotoxemia) has a small but highly significant genetic component. Endotoxemia is associated with genetic variation in the contact activation pathway, vasoactivity, and lipoprotein metabolism, which play important roles in host defense, lipopolysaccharide neutralization, and thrombosis, and thereby thromboembolism and stroke.