INTRODUCTION:Body mass index (BMI) fluctuation has adverse health consequences, yet its determinants remain poorly understood. We examined genetic and environmental influences on BMI fluctuation and its associations with BMI trajectories. DATA AND METHODS:Data from 14 longitudinal twin cohorts, including 58 311 individuals (54% women) and 22 714 complete twin pairs (9761 monozygotic), were pooled. BMI trajectories from ages 18 to 99 years were estimated using linear mixed-effects models. BMI fluctuation was defined as the average squared residual between observed and expected BMI around individual trajectories. Genetic and environmental contributions to BMI fluctuation and its associations with baseline BMI and BMI change were assessed using structural equation modelling. RESULTS:Additive genetic effects explained a moderate proportion of variance in BMI fluctuation (a2 = 0.20 in men, 0.29 in women), with the remainder attributable to unique environmental effects (e2 = 0.80 and 0.71). No evidence of sex-specific genetic effects was found. Genetic contributions varied across life stages, peaking in men at ages 31-50 (a2 = 0.36) and in women at 51-65 (a2 = 0.36). Higher baseline BMI was associated with greater fluctuation, whereas greater directional BMI change was associated with less fluctuation. Higher BMI at ages 18-30 was associated with greater subsequent BMI fluctuation across later adulthood stages. Previous associations were driven by both genetic and unique environmental factors. CONCLUSIONS:BMI fluctuation was predominantly explained by unique environmental effects, with moderate heritability that varied across life stages with no evidence of sex-specific genetic effects. Genetic and environmental factors contribute to how BMI fluctuation is associated with BMI change.

INTRODUCTION:Educational attainment (EA) is negatively associated with body mass index (BMI), but less is known about the association between EA and adult BMI change. We analysed the role of genetic and environmental factors in the associations between EA and BMI trajectory components over adulthood. DATA AND METHODS:Pooled data from 59,490 twins aged 31-99 years (49% women) across 11 cohorts with EA and repeated measures of BMI were used. BMI trajectory components (baseline BMI and BMI change per decade) were estimated using linear mixed-effects (LME) and delta slope methods. EA was derived by regressing years of education on birth year and cohort. Associations between EA and BMI trajectories were evaluated with LME models in both cohort-specific and pooled data. Genetic and environmental contributions were evaluated using structural equation modelling. RESULTS:EA was more strongly negatively associated with baseline BMI and BMI change (mean of 1.31 and 1.32 kg/m2 per decade in men and women, respectively) in women (β = -0.14 kg/m², 95% CI: -0.15 to -0.12; β = -0.02 kg/m²/decade, 95% CI: -0.03 to -0.01, respectively) than in men (β = -0.07, 95% CI: -0.08 to -0.06; β = -0.01, 95% CI: -0.02 to -0.001, respectively). The associations between baseline BMI and EA were explained by genetic factors in men (rA = -0.10) and by both genetic (rA = -0.17) and unique environmental factors (rE = -0.07) in women. For BMI change, the associations with EA were explained by genetic factors (rA = -0.04 in men; -0.06 in women). CONCLUSION:Individuals with higher EA tend to have lower baseline BMI and slower BMI increases across adulthood. These associations are primarily genetically mediated.

The transition to parenthood is a significant life event that can influence various aspects of individuals’ lives, including alcohol consumption patterns in the long term. This study examines alcohol use changes in relation to parenthood in two Finnish cohorts. Data were derived from two follow-up studies: Stress, development and mental health (TAM) (ages 16, 22, 32, 42, and 52) and the FinnTwin16 cohort (ages 16, 18, 25, and 35). We used generalized linear mixed models to examine the association between parenthood years and alcohol use from adolescence to mid-adulthood. Frequent alcohol use (FAU) and heavy episodic drinking (HED) were examined separately. Frequent alcohol use increased with age in both cohorts, while heavy episodic drinking peaked in late adolescence among women and in young adulthood among men. Prior to parenthood, alcohol use was generally lower in the earlier years and increased as the transition to parenthood approached in FinnTwin16. Heavy episodic drinking declined in the early years following the transition to parenthood, while frequent alcohol use remained stable. In both women and men, long-term increases in alcohol use were observed around 7 years after becoming a parent. Differences between parents and non-parents were minimal. These findings suggest that parenthood is associated in particular with short-term reductions in heavy episodic drinking, but that overall alcohol use tends to increase over time.

Integrating curriculum-based outdoor education (OE) into pedagogical practices in primary schools holds potential for health promotion as an alternative to sedentary classroom settings, but it remains understudied. We investigated associations between OE and children's school- and leisure-time physical activity (PA) throughout the week and possible differences between boys and girls in the associations. This 1-week cross-sectional study conducted in primary schools in Finland (2021-3) used accelerometer-measured PA data from 200 children aged 8-13 years, teacher-reported logbook data on OE, and questionnaire data on sociodemographics. Fifty-two percent of the children had no OE during the study period, whereas the other half had 25-335 minutes (mean 63 minutes). In linear regression models adjusted for sociodemographics, physical education, and season, low to moderate amounts of OE (25-60 minutes during study period), compared to no OE, were associated with 1.2 minutes/hour more moderate to vigorous-intensity PA (MVPA) and 1.8 minutes/hour more total PA (TPA) during school time among all children. The highest amounts of OE (120-335 minutes during study period) were associated with 2.7 minutes/hour more light-intensity PA and 2.8 minutes/hour more TPA on weekend days. Gender moderated some associations; the highest amounts of OE were associated with 3.5 (boys) and 4.8 (girls) minutes/hour more MVPA during school time and, among girls, with 4.2 minutes/hour more TPA during school time and 1.5 minutes/hour more MVPA and 2.2 minutes/hour more TPA on weekdays. These findings suggest that integrating OE into the school day may support PA throughout the week, particularly among girls.

Purpose: Physical activity (PA) among children has decreased in recent decades, raising serious health concerns. Integrating more movement into the school day has been suggested as a method of promoting PA. In this study we investigated the association between curriculum-based outdoor education (OE) and PA among school-aged children, focusing on total PA (TPA) and time spent in different intensities of PA on weekdays, weekend days, during schooltime, leisure time on weekdays, and as daily average. Methods: This cross-sectional study is part of the LärMiljö (Learning Environment) study, conducted in Swedish-language primary schools (grades 3–6, ages 9–13 years) in seven municipalities in Finland. Data were collected in 2021–2023 from 260 children, their caregivers, and class teachers. Children’s PA was measured for seven consecutive days using hip-worn accelerometers (ActiGraph). The use of OE was reported by the class teacher in an electronic logbook on the same days as the children wore accelerometers. Sociodemographic characteristics were reported by children and caregivers in questionnaires. Linear regression analyses were conducted adjusting for gender, grade, accelerometer wear days, physical education during study period, season of participation, and socioeconomic status. Results: Of the children participating in the study, 200 (77%) met the criteria for valid device-based PA data and teacher-reported OE data and were included in the analyses. Approximately half (52%) of them had no OE during the study period, whereas the other half had 25–335 minutes of OE. The fully adjusted regression models showed that a higher amount of OE was associated with more moderate-to-vigorous PA (MVPA) as daily average and during schooltime, lighter PA (LPA) and TPA on weekend days, but less LPA during schooltime. In girls, a higher amount of OE was also associated with more TPA during schooltime, and more MVPA and TPA on weekdays. Conclusion: The findings highlight the potential of integrating OE into teaching to promote PA in school-aged children. In addition, our results suggest that girls may benefit even more than boys from participating in OE in terms of PA. Support/Funding Source: Folkhälsan Research Center, The Swedish Cultural Foundation in Finland, Stiftelsen Eschnerska Frilasarettet sr Foundation.

Aging is accompanied by a decline in physiological function and increased vulnerability to disease, with mitochondrial dysfunction and epigenetic alterations recognized as key hallmarks. Nicotinamide riboside (NR), a vitamin B3 precursor to NAD+, and high-intensity interval training (HIIT) have both been proposed to ameliorate aging-related mitochondrial decline, but their effects on skeletal muscle epigenetic aging are not fully elucidated. Here, we assessed the impact of 5-month NR supplementation and 4-6 weeks HIIT on epigenetic age acceleration (EAA, via seven epigenetic clocks) in human skeletal muscle across three independent studies. NR supplementation was associated with reduced muscle EAA, particularly when measured with the PCHannum, MEAT, and DunedinPACE clocks, while HIIT produced opposite effects in some clocks, notably increasing pace of aging by DunedinPACE. Correlation analyses revealed that changes in skeletal muscle mitochondrial content correlated with changes in MEAT-derived EAA after NR and 6 weeks of HIIT. Together, these findings indicate that skeletal muscle epigenetic aging can be modulated by NR and HIIT interventions but in opposing directions, highlighting a potential link between mitochondrial abundance and epigenetic clocks. Further studies are warranted to clarify how NR and exercise regulate epigenetic aging. These results offer new insights into development of strategies for promoting epigenetic outcomes and healthy aging.

Objective BMI is influenced by both genetic and environmental factors, including features of the obesogenic environment such as walkability. This study investigated the interplay between residential walkability, genetics, and BMI among 4312 individuals from two Finnish twin cohorts (mean age: 43).Methods Residential walkability was quantified using a composite index including built and natural environmental features.Results Multiple linear regression, adjusted for sociodemographic factors, showed that higher walkability was associated with lower BMI (coefficient: -0.02, 95% CI: -0.04, -0.01), but pairwise twin analyses indicated that this association was not independent of genetic and early shared environmental influences. Univariate twin modeling revealed that additive genetic effects accounted for 22% of the variation in walkability when participants were middle-aged. Bivariate moderation twin modeling showed that the additive genetic influence on BMI was significantly stronger among individuals living in areas with average or moderately low residential walkability. The unique environmental component played a larger role among those living in areas with either very low or very high residential walkability.Conclusions These findings underscored the complex gene-environment interplay between walkability and BMI. While genetic susceptibility cannot be modified, public health strategies that focus on the obesogenic environment, such as improving walkability, may still help mitigate obesity risk.

OBJECTIVES:In short follow-up studies, greater leisure-time physical activity (LTPA) has been associated with better cognition in old age, but more longitudinal studies are needed. Our aim was to identify long-term LTPA trajectories from midlife to late old age and examine whether these trajectories are associated with nonagenarians' cognition. METHODS:In total, 125 participants from the NONAGINTA-Memory and Health in Nonagenarians study were included. The participants responded to health surveys of the older Finnish Twin Cohort study, including LTPA at the mean ages of 45, 52, 59, and 91 years. Cognition was assessed at the mean age of 91 years (standard deviation 1.54) via telephone interview (global cognitive function, episodic memory, and semantic fluency). We identified LTPA trajectories with K-means clustering for longitudinal data, and we used generalized estimating equations models to investigate differences in cognition among the LTPA trajectories. Covariates included age, sex, and education. RESULTS:We found 3 LTPA trajectories from midlife to nonagenarian age. The largest proportion of participants belonged to the Constant low trajectory (52%), characterized by a stable low level of physical activity throughout the follow-up. Two other trajectories were Starting low and increasing (25%) and Starting high and decreasing (23%). Nonagenarians' cognitive measures did not differ among the LTPA trajectories. DISCUSSION:Longitudinal physical activity behavior may not preserve cognitive function in those who survive to nonagenarian age but larger studies are warranted.

Abstract Background Previous studies have presented conflicting findings regarding the potential causal relationships between leisure-time physical activity (LTPA) and body mass index (BMI). Here, we use individual-level data and apply a triangulation framework that incorporates three complementary methods to investigate the bidirectional causal associations between LTPA and BMI. Methods We used data from a longitudinal Finnish twin cohort with four measurement points spanning 36 years. The data included 22,696 twin individuals aged 18-50 years at baseline (52.4% women); 8,527 had genetic data available. We applied three analytical approaches suggested to strengthen causal inference in observational studies: Random intercept cross-lagged path model (RI-CLPM) for longitudinal data, one-sample Mendelian Randomization (MR) and Direction of Causation (DoC and MR-DoC) twin models for cross-sectional data at each measurement point. Results All three approaches provided evidence for a causal effect of higher BMI on lower LTPA, particularly at the later follow-up stages. Only twin models suggested a negative causal effect of LTPA on BMI. Men and women showed mainly similar effects. Conclusions Evidence triangulation across the three methodologies provided support for a causal effect of higher BMI on lower LTPA, whereas the evidence for a reverse effect was less convincing. Our results indicate that the role of high BMI in limiting LTPA becomes more important with advancing age, while also highlighting the importance of accounting for timing when studying the causal effects of LTPA on BMI and vice versa.

We investigated longitudinal associations between adolescent attention-deficit/hyperactivity disorder (ADHD) symptoms and later antisocial behavior and tested 1) whether these associations are independent of familial factors shared by co-twins and 2) whether cognitive performance moderates the associations. In a population-based sample of Finnish twins (N = 602-1330, 53% female), we assessed ADHD symptoms with teacher assessments and a diagnostic interview in adolescence, symptoms of antisocial personality disorder with a diagnostic interview in young adulthood, and criminal behavior across the lifespan with self-reports in early midlife. Cognitive performance was assessed with commonly used test measures in young adulthood. Adolescent ADHD symptoms were consistently associated with an increased risk for antisocial symptoms (incidence rate ratio [IRR] = 1.18-1.27) and criminal behavior (IRR = 1.16-1.20) later in life. Within-pair and interaction analyses suggested that the associations were to a large degree independent of familial factors, and cognitive performance level did not moderate them. In conclusion, subclinical ADHD symptoms are associated with an increased risk for antisocial behavior at the population level. The association is not fully explained by familial background, and it is independent of cognitive performance level.

Genetic and environmental factors contribute to weight gain, but how these effects change over adulthood is largely unknown. We examined how genetic factors influence BMI changes from young adulthood to old age and how this change relates to BMI in early adulthood. Data from 16 longitudinal twin cohorts, including 111,370 adults (56

Background:Depression is a major public health concern with a complex etiology, which may also be influenced by the living environment. The first-person visibility represents the most direct way of influence from the physical environment. Objectives:We aim to investigate the effect of the visibility of the environment at the residence on self-reported depression among early midlife adults, as well as underlying gene-environment interplay. Methods:The study used 1867 participants who completed the early midlife follow-u p (mean age: 37.2 years) of the FinnTwin12 cohort. The visibility of the environment at the residence was segmented into three visibility factors: sky, tree, and building. Linear regression was fitted between visibility factors and self-reported depression. Molecular methods using polygenetic risk score and twin design (univariate modeling and bivariate moderation modeling) were applied to explore the gene-environment correlation and interaction. Findings:In males, a higher proportion of building visibility factor was associated with more depression (beta: 0.20, 95% CI: 0.03, 0.36). Univariate twin models estimated that additive genetic factors accounted for 46%, 29%, and 49% of the variance in sky, tree, and building visibility factors, respectively. Bivariate moderation analyses revealed strong gene-environment interactions between all three visibility factors and self-reported depression in females, while in males, interaction was observed by the building visibility factor. Conclusion:Urban design should consider building density and other related characteristics to promote mental well-being. The complex gene-environment interplay informs the need for tailored interventions that account for genetic susceptibility and processes by which persons select their inhabitats.

We examined the associations of midlife and old-age cardiovascular risk factors, education, and midlife dementia risk scores with cognition at 90 + years, using data from a population-based study with 48 years of follow-up. Participants were 96 individuals aged 90-97 from the older Finnish Twin Cohort study. Individual cardiovascular risk factors assessed via questionnaires in 1975, 1981, 1990, and 2021-2023 included blood pressure, body mass index, physical activity, and cholesterol, and self-reported educational attainment. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score and an educational-occupational attainment score were used as midlife dementia risk scores. Cognitive assessments included semantic fluency, immediate and delayed recall from a 10-word list learning task, and a composite cognitive score. Regression analyses were conducted with dementia risk factors predicting cognition at 90 + years, adjusting for age, sex, education, follow-up time, and apolipoprotein E genotype (ε4-carrier vs non-carriers). Results showed that higher education and higher educational-occupational score were associated with better cognitive performance in all cognitive measures. Those with high midlife blood pressure scored significantly higher in all cognitive tests than those with normal blood pressure. Conversely, those with high old-age blood pressure scored lower in semantic fluency and composite cognitive score, but not in immediate or delayed recall. Other cardiovascular risk factors and the CAIDE score did not show consistent associations with cognition. Education appears to have a long-lasting protective effect in cognitive aging, whereas midlife and old-age cardiovascular risk factors were not significantly associated with cognition at 90 + years.

This paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g., parenthood). In total, 2,085 individuals (~40% of the original sample) completed the survey (551 complete twin pairs, 58.7% female, 37.3% monozygotic, age range = 34-39 years). Individuals who participated were more likely to be female, monozygotic, and have higher parental education and less hyperactivity/impulsivity and aggression at age 12 when compared to individuals who were invited but did not participate. Parental alcohol misuse and the twins’ alcohol use and misuse at age 14 were not related to study retention. Alcohol misuse in early midlife was positively associated with nicotine dependence, lifetime use of cannabis and other drugs, trauma exposure, and depressive symptoms, and negatively associated with physical health and having biological children. These new data expand upon the wealth of measures collected as part of previous assessments, expanding the scope of work on the etiology and correlates of alcohol misuse across within a longitudinal, genetically-informed framework. In addition to these new survey measures, we are planning an in-person assessment to collect physiological measurements and conduct additional in-depth phenotyping on a subset of twins who have been more intensively studied over the years.

Glucose metabolism and related blood molecules are strongly associated with adult body mass index (BMI). However, it is unclear whether the magnitude of these associations differs in people whose BMI increased rapidly during adolescence or who have a genetic predisposition to high BMI. The analyses included 373 Finnish participants (39% males) with BMI data at approximate ages 11.5, 14, 17.5, 22, and 37 years. BMI trajectories (defined as BMI changes (i.e. slope) and BMI baseline (i.e. intercept)) were calculated during adolescence (from 11.5 to 17.5 years of age) using linear mixed-effects (LME) models and adulthood (from ∼22 to 37 years of age). We employed LME models to quantify the associations between BMI trajectories during adulthood and nine plasma molecules related to glucose metabolism measured at age ∼22 years. For significant associations, we tested whether the levels of the molecules interacted with either changes in BMI during adolescence or a Polygenic Risk Score (PRS) of BMI (PRS BMI ). Stratified analyses were performed for men and women. During adulthood, BMI changes per year were 0.16 kg/m 2 in men and 0.17 kg/m 2 in women. The analysis revealed seven statistically significant associations between plasma molecules with adult BMI, but no associations with weight change during adulthood. Four statistically significant interactions with plasma molecules were identified, all of which were found in women. In predicting BMI at ∼22 years old, BMI changes in adolescence interacted positively with glucose (p=2.0e-04) and negatively with citrate levels (p= 5.6e-04), and the PRS BMI interacted positively with glucose (p= 3.4e-04) and negatively with citrate (p= 8.3e-03). The current study provides evidence that PRS BMI and BMI changes during adolescence modulate the associations between BMI during adulthood with glucose and citrate blood levels in women.

Loneliness—a mismatch between desired and existing social relationships—has been linked to an increased dementia risk, but the nature of this association remains unclear and may involve reverse causation. Personality traits, such as higher neuroticism and lower extraversion, are also associated with both dementia risk and loneliness. Few studies, however, have accounted for personality when examining the relationship between loneliness and cognitive aging. This study aims to clarify the association between midlife loneliness and late-life cognition by considering the potential moderating role of personality, using a long follow-up up to 23 years. Participants from the older Finnish Twin Cohort completed questionnaires in 1975, 1981, and 1990. Current feeling of loneliness was measured in all questionnaires with one item with three response options (very lonely, fairly lonely, not lonely). Neuroticism and extraversion were based on an abbreviated Eysenck’s Personality Inventory in 1975 and 1981. Covariates included sex, age, education, Cardiovascular Risk Factors, Aging and Dementia score, alcohol use, smoking status, depression status, social contact frequency, and marital status. Cognitive data were collected in 2013–2017 from 1814 individuals aged 71–79 (mean age 34 in 1975) using the Telephone Interview for Cognitive Status–modified (TICS-m). ApoE status was determined from DNA arrays. Participants were grouped as consistently lonely ( n =202), never lonely ( n =1238), or with varying loneliness ( n =127). Loneliness profile and extraversion did not predict cognition, after adjustment for covariates. Higher neuroticism predicted worse cognition when adjusting for age, sex, and education (β = -0.127, p = 0.045), one-point increase in neuroticism was linked to a 0.13-point decrease in TICS-m (0–50), but this was not significant after adjusting for other covariates. No significant interaction effects were found between loneliness profile, personality traits, and cognition. Covariates age, education, depression status, social contact frequency, and ApoE status consistently predicted cognitive scores. Midlife loneliness was not associated with late-life cognitive functioning. While neuroticism showed a modest link to lower cognition, this did not persist after including all covariates. These findings suggest that loneliness and personality in midlife may not be independent risk factors for late-life cognitive decline when broader health and lifestyle factors are considered.

OBJECTIVE:The aim of this prospective cohort study was to examine the incidence and characteristics of injuries in professional ballet dancers across multiple seasons. METHODS:Hundred-and-sixteen ballet dancers (median age 24; range 18-40, females 53%) from a professional ballet company agreed to participate and were followed for up to five ballet seasons. All dance-related injuries requiring a visit to a medical doctor were recorded by in-house physiotherapists. Injury rates per 100 dancer seasons were calculated and injury characteristics (i.e. anatomical location, tissue type, severity, and mechanism) were described. RESULTS:Hundred-and-sixty injuries occurred in 311 dancer-seasons, comprising an injury rate (IR) of 51.5 injuries (95% CI 45.9 to 57.0) per 100 dancer-seasons. Eighty-three percent of the injuries affected the lower limbs (IR 42.4, 95% CI 37.0 to 47.9). The ankle was the most injured body region (IR 15.4, 95% CI 11.4 to 19.5), followed by lower leg (IR 8.4, 95% CI 5.3 to 11.4), and knee (IR 6.1, 95% CI 3.5 to 8.8). Thirty-nine percent of injuries involved muscle/tendon structures, and 29% involved ligaments/joints. Fifty-seven percent of injuries were severe, causing more than 28 days absence from dance. Of all injuries, 57% were sudden onset, and 43% were gradual onset injuries. CONCLUSION:Results highlight the need for effective interventions to reduce the high incidence of lower limb injuries, including ankle sprains, tendon issues, muscle strains, and stress fractures in professional ballet dancers.

Cardiovascular (CV) risk factors are associated with increased dementia risk, but their effects on cognition in the oldest-old (90+) are not well studied. CV risk factors may appear to be protective against dementia due to reverse causation when they are measured during dementia process. To clarify this, we studied CV risk factors measured both at midlife and old age, with 48 years of follow-up. We had 96, 90-97-year-olds from the NONAGINTA study consisting of population based older Finnish Twin Cohort study participants born in 1922-1933. CV risk factors included blood pressure (BP), body mass index (BMI), and physical activity (PA) assessed via questionnaires in 1975, 1981 and 2021-2023, and cholesterol in 2021-2023. Telephone-administered cognitive measures included semantic fluency (1-minute animal naming), and immediate and delayed recall of three trial 10-word list learning. We used linear and negative binomial regression analyses (delayed recall) with CV risk factors as independent variables (age, sex, education, and Apolipoprotein E genotype as covariates and adjusted for family data) and 90-year-old cognition as a dependent variable. Those with 7-11 years and ≥12 years of education had better immediate recall than those with ≤6 years of education (p = 0.003 & p<0.001). Those with ≥12 years (n = 19) of education also scored higher than those with ≤6 years of education both in semantic fluency and delayed recall (p<0.001). Higher middle-age BMI was associated with better animal fluency (p = 0.011), but not with immediate or delayed recall. Old-age BMI or cholesterol, and middle-age or old-age PA were not related to cognition. Those with high middle-age BP (n = 6) scored higher in animal fluency (p = 0.005), immediate recall (p = 0.023) and delayed recall (p = 0.003) than those with normal BP. In contrast, those with high old-age BP (n = 63) scored lower in animal fluency (P = 0.010), but not in immediate or delayed recall. The most robust finding was that higher (secondary) education is associated with better cognition even in late old-age. Middle-age high BP was associated with better old-age cognition, but this relationship was reversed for old-age BP. Paradoxical positive effect of high midlife BP may reflect earlier start of BP medication.