The brain insulin receptor gene network and associations with frailty index.

OBJECTIVE: To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up. METHODS: This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001-2004, 2011-2013 and 2017-2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age. RESULTS: The FI levels of women were 1.19%-points (95% CI 0.12-2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increase in mean FI levels per year in either sex (P > 0.43). CONCLUSIONS: Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study.

BACKGROUND: Few studies have examined longitudinal changes in lifestyle-related factors and frailty. METHODS: We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57-69 years at baseline. RESULTS: A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted ß × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted ß × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted ß × Time = -0.10, 95%CI = -0.23, -0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted ß × Time = 0.16, 95% CI = 0.01, 0.30). CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.

Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age: A Longitudinal Birth Cohort Study.

INTRODUCTION: Few studies have investigated the association between frailty and subsequent body composition. METHODS: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. RESULTS: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with "stable frailty," followed by those with "increasing frailty" experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group "stable not frail." Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third. CONCLUSIONS: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.

Depressive symptoms and mortality-findings from Helsinki birth cohort study.

BACKGROUND: Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon. METHODS: One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated. RESULTS: Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02-2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85-1.44)] and melancholic depressive [1.26 (95% CI: 0.87-1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73-0.93)]. CONCLUSIONS: Melancholic depressive symptoms are most strongly related to a higher mortality risk.

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case-control study.

BACKGROUND: Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. METHODS: This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. RESULTS: We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, HbA1c, and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. CONCLUSIONS: We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.

Effect of childhood developmental coordination disorder on adulthood physical activity; Arvo Ylppö longitudinal study.

Individuals at risk of Developmental Coordination Disorder (DCD) have low levels of physical activity in childhood due to impaired motor competence; however, physical activity levels in adulthood have not been established. This study sought to determine the impact of DCD risk on physical activity levels in adults using accelerometry measurement. Participants (n = 656) from the Arvo Ylppö Longitudinal Study cohort had their motor competence assessed at the age of five years, and their physical activity quantified via device assessment at the age of 25 years. Between group differences were assessed to differentiate physical activity measures for individuals based on DCD risk status, with general linear modeling performed to control for the effects of sex, body mass index (BMI), and maternal education. Participants at risk of DCD were found to have a lower total number of steps (d = 0.3, p = 0.022) than those not at risk. Statistical modeling indicated that DCD risk status increased time spent in sedentary light activity (ß = 0.1, 95% CI 0.02 to 0.3, p = 0.026) and decreased time spent in vigorous physical activity via interaction with BMI (ß = 0.04, 95% CI 0.001 to 0.1, p = 0.025). Sensitivity analysis found that visuomotor impairment did not significantly impact physical activity but did increase the role of DCD risk status in some models. This 20-year-longitudinal study indicated that DCD risk status continues to negatively impact on levels of physical activity into early adulthood.

Maternal body mass index, change in weight status from childhood to late adulthood and physical activity in older age.

This study aimed to examine the longitudinal associations of maternal body mass index (BMI), weight status in childhood and late adulthood and device-measured total physical activity (TPA) in older age. The study involves 552 participants from Helsinki Birth Cohort Study who were born in Helsinki, Finland, in 1934-1944. TPA was measured with a multisensory body monitor at a mean age of 70 years and expressed in metabolic equivalent of task hours/day (METh/d). Childhood overweight (BMI > 85th percentile) was based on school health records at 6-7 years of age, and late adulthood overweight (BMI ≥ 25 kg/m2 ) was based on clinical measurements at the mean age of 61 years. Childhood overweight was associated with lower TPA, particularly in older women (mean difference -3.2 METh/d, 95% confidence interval (CI) -4.6 - -1.9), and late adulthood overweight was associated with lower TPA both in older women (mean difference -6.2, 95% CI (-7.2 - -5.1) and in older men (mean difference -2.6 METh/d, 95% CI -3.7 - -1.5). TPA in older age was highest in participants who were normal weight both in childhood and adulthood and lowest in participants who were overweight in childhood and adulthood. In participants with childhood overweight, TPA was lower in participants who were overweight both in childhood and adulthood compared to those who were overweight only in childhood. There was a U-shaped distribution of TPA according to maternal BMI in older women (P = .002), but not in older men. In conclusion, reaching normal weight after childhood predicted higher physical activity levels in older age.

Body composition and changes in health-related quality of life in older age: a 10-year follow-up of the Helsinki Birth Cohort Study.

PURPOSE: Most studies examining the associations between body composition and health-related quality of life (HRQoL) in older age have been cross-sectional and analyzed only fat or lean mass. Hence, it is poorly known whether fat and lean mass are independently associated with subsequent changes in HRQoL. We investigated whether baseline lean and fat mass are associated with changes in HRQoL over a 10-year period in older adults. METHODS: We studied 1044 men and women from the Helsinki Birth Cohort Study (age 57-70 years at baseline). Bioelectrical impedance analysis was used to derive baseline fat mass index (FMI, fat mass/height2) and lean mass index (lean mass/height2), dichotomized at sex-specific medians. HRQoL was assessed using RAND 36-item Health Survey at baseline and follow-up 10 years later. RESULTS: When controlled for lean mass and adjusted for potential confounders, high baseline FMI was associated with a greater decline in general health (standardized regression coefficient [ß] = - 0.13, p = 0.001), physical functioning (ß = - 0.11, p = 0.002), role physical (ß = - 0.13, p = 0.003), vitality (ß = - 0.08, p = 0.027), role emotional (ß = - 0.12, p = 0.007), and physical component score (ß = - 0.14, p < 0.001). High baseline FMI was also associated with low HRQoL in all physical domains at baseline (ß: from - 0.38 to - 0.10). Lean mass was not strongly associated with HRQoL at baseline or change in HRQoL. CONCLUSION: In older community-dwelling adults, higher fat mass is, independent of lean mass, associated with lower physical HRQoL and greater decline in HRQoL. Prevention of adiposity may contribute to preservation of a good quality of life in older age.

Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study.

BACKGROUND: Telomeres are crucial parts of chromosomes that protect the genome. They shorten every time the cell replicates, and shorter telomeres have been associated with increasing age and with many health behaviours. There is inconclusive evidence on the association between physical activity (PA) and telomere length. OBJECTIVES: To examine how leisure-time PA (LTPA) is associated with telomere length and telomere attrition during 10 years of follow-up in elderly people. DESIGN: This study is a 10-year prospective follow-up study. METHOD: For this prospective study, we examined 1,014 subjects (mean age at baseline 60.8 years) from the Helsinki Birth Cohort Study (HBCS). Relative leukocyte telomere length (LTL) was measured with a quantitative real-time PCR and LTPA with a validated questionnaire. Multiple linear regression analyses were used to assess the association between sex-specific LTPA quartiles and LTL at baseline and change in LTL over 10 years. The analyses were adjusted for age, educational attainment, smoking, body fat percentage, oestrogen exposure in women and for follow-up time when applicable. RESULTS: At baseline, volume of LTPA was not associated with LTL in men (p = 0.66) or in women (p = 0.33). Among women, however, higher volume of LTPA at baseline was associated with greater shortening of LTL (p for linearity 0.040) during the 10-year follow-up. No association was found among men (p for linearity 0.75). CONCLUSIONS: Our findings suggest that PA has a sex-specific role in regulation of telomere length in the aging process as in our study a high volume of LTPA in elderly women, but not in men, was associated with more rapid telomere attrition.

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts.

BACKGROUND: The study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI. METHODS: We studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n = 5807, NFBC1986, n = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934-1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex. RESULTS: The association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (ß = 0.79, 95% CI, 0.33, 1.25, p < 0.001) in NFBC1966. In NFBC1986 this association was attenuated by PRS BMI (p = 0.181), and in HBCS1934-1944 there was no association between high early social disadvantage and increased later life BMI (ß 0.22, 95% CI -0.91,1.35, p = 0.700). In HBCS1934-1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (ß - 1.34, [- 2.37,-0.31], p = 0.011; ß - 0.46, [- 0.89,-0.03], p = 0.038, respectively). CONCLUSIONS: High social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.

Change in physical activity and health-related quality of life in old age-A 10-year follow-up study.

The aim of the study was to examine the association between change in leisure-time physical activity (LTPA) and change in health-related quality of life (HRQoL) and symptoms of depression during a 10-year follow-up. This prospective study included 1036 men and women (mean age at baseline = 61.2 years) from the Helsinki Birth Cohort Study. Leisure-time physical activity was measured with a questionnaire, HRQoL with SF36 and depression symptoms with Beck's depression inventory (BDI). The association between the change in LTPA and change in HRQoL and BDI were investigated with sex-stratified general linear models adjusted for age, smoking, educational attainment, comorbidity score, and baseline value of outcomes. One standard deviation (SD) increase in LTPA was associated with increase in physical summary component of HRQoL in women (B = 0.7 unit, 95% CI = 0.1-1.3, P = 0.032) and in men (B = 0.8 unit, 95% CI = 0.2-1.5, P = 0.014). In women, the 1SD increase in LTPA was also associated with an increase in mental summary component score (B = 1.0, 95% CI = 0.3-1.7, P = 0.005) and a reduction in depressive symptoms (B = -0.7, 95% CI = -1.1 to -0.2, P = 0.003). In conclusion, increase in the volume of LTPA over a 10-year period in late adulthood was associated with improved HRQoL in both men and women, and also diminished depressive symptoms in women. The findings support the promotion of physical activity in later years to enhance HRQoL and mental well-being.

Effects of a Preschool Intervention on Physical Activity and Body Composition.

OBJECTIVE: To investigate the effect of a preschool physical activity intervention program delivered in licensed childcare settings, with or without a parent-facilitated home component, on children's daily physical activity, sedentary time, and body composition. STUDY DESIGN: For this cluster randomized controlled trial, 18 childcare centers were randomly allocated in equal numbers to the typical curriculum comparison group, childcare intervention alone (CC), or childcare intervention with parental involvement. Accelerometers were used to asses physical activity and sedentary time, and body composition was measured by bioelectrical impedance. RESULTS: Linear mixed model regression analyses showed no differences between the CC, the childcare intervention with parental involvement, and the comparison groups in changes from baseline to 6 months in total physical activity (P for time × group interaction = .665) or moderate-to-vigorous physical activity (P for time × group interaction = .164) when adjusted for baseline physical activity levels. Furthermore, no group differences were found for changes in light physical activity, sedentary time, or anthropometric variables. CONCLUSIONS: An affordable and easily scalable preschool intervention program delivered in licensed childcare settings, with or without the addition of a parent-driven home physical activity promotion, seems to have no significant effect on physical activity, sedentary time, or body composition. TRIAL REGISTRATION: ISRCTN: ISRCTN94022291.

Objectively measured physical activity and physical performance in old age.

Background: physical performance is a key factor that determines how older people cope with daily tasks and maintain independency. There is strong evidence suggesting that physical activity (PA) is important in maintaining physical performance in old age. However, most studies have been done using self-reported PA. Our aim was to explore the association between objectively measured PA and physical performance in old age. Methods: we studied 695 participants (mean age 70.7 years, SD 2.7) from the Helsinki Birth Cohort Study. Physical performance was assessed with the Senior Fitness Test (SFT) and PA with a multisensory activity monitor SenseWear Pro 3 Armband. Results: total volume of PA was significantly associated with the overall SFT score (ß = 0.08; 95% confidence interval: 0.07-0.10, P < 0.001). There were no significant differences between men and women. Both light and moderate to vigorous level of PA were positively associated with the overall SFT score, while sedentary time was negatively associated with the overall SFT score. Conclusions: volume of objectively measured PA among older people was positively associated with the physical performance measured with a validated fitness test battery.

Interaction between rs10830963 polymorphism in MTNR1B and lifestyle intervention on occurrence of gestational diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the interaction between melatonin receptor 1B gene (MTNR1B) rs10830963 polymorphism and lifestyle intervention during pregnancy on occurrence of gestational diabetes mellitus (GDM) in high-risk women. METHODS: This is a secondary analysis of the randomised controlled gestational diabetes prevention trial 'RADIEL', conducted between 2008 and 2014 in four maternity hospitals in southern Finland. A total of 226 women with a history of GDM and/or a pre-pregnancy BMI ≥ 30 kg/m(2) were enrolled at <20 weeks of gestation (mean 13 weeks) and randomised into an intervention group receiving counselling on diet, physical activity and weight control and a control group receiving standard antenatal care. The main outcome was incidence of GDM, defined as one or more pathological glucose values in a standard 75 g 2-h OGTT. The MTNR1B rs10830963 was genotyped for further analyses. RESULTS: No significant differences were found in the genotype distribution between the intervention and the control group. A significant interaction was observed between the rs10830963 genotypes and the lifestyle intervention on age-adjusted occurrence of gestational diabetes (p = 0.038). Among women homozygous for the C allele of rs10830963, the OR for GDM was significantly lower in the intervention group than in the control group (OR 0.16 [95% CI 0.03, 0.85], p = 0.014). This difference was not seen in women heterozygous (OR 0.88 [95% CI 0.32, 2.41], p = 0.798) or homozygous (OR 2.25 [95% CI 0.34, 14.69], p = 0.384) for the risk allele G. CONCLUSIONS/INTERPRETATION: In women at high risk of GDM, only those not carrying the risk allele G benefited from the lifestyle intervention. Our results indicate that certain genetic risk variants may modify the effectiveness of lifestyle interventions. This may provide important information when planning GDM prevention studies in the future.

Intellectual ability in young adulthood as an antecedent of physical functioning in older age.

OBJECTIVES: low cognitive ability is associated with subsequent functional disability. Whether this association extends across adult life has been little studied. The aim of this study was to examine the association between intellectual ability in young adulthood and physical functioning during a 10-year follow-up in older age. METHODS: three hundred and sixty persons of the Helsinki Birth Cohort Study (HBCS) male members, born between 1934 and 1944 and residing in Finland in 1971, took part in The Finnish Defence Forces Basic Intellectual Ability Test during the first 2 weeks of their military service training between 1952 and 1972. Their physical functioning was assessed twice using the Short Form 36 (SF-36) questionnaire at average ages of 61 and 71 years. A longitudinal path model linking Intellectual Ability Test score to the physical functioning assessments was used to explore the effect of intellectual ability in young adulthood on physical functioning in older age. RESULTS: after adjustments for age at measurement, childhood socioeconomic status and adult BMI (kg/m(2)), better intellectual ability total and arithmetic and verbal reasoning subtest scores in young adulthood predicted better physical functioning at age 61 years (P values <0.021). Intellectual ability total and arithmetic and verbal reasoning subtest scores in young adulthood had indirect effects on physical functioning at age 71 years (P values <0.022) through better physical functioning at age 61 years. Adjustment for main chronic diseases did not change the results materially. CONCLUSION: better early-life intellectual ability helps in maintaining better physical functioning in older age.

A former career as a male elite athlete--does it protect against type 2 diabetes in later life?

AIMS/HYPOTHESIS: The aim of this study was to determine the prevalence of impaired glucose regulation in male Finnish former elite athletes and age- and area-matched controls. We hypothesised that vigorous physical activity during young adulthood protects from disturbances in glucose regulation in later life. METHODS: In 2008, 392 former male elite athletes (mean age 72.7 ± 6.1 years) and 207 controls (mean age 71.6 ± 5.6 years) participated in a clinical study (participation rate: 50.6%). The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Participants without a history of diabetes (n = 537) underwent a 2 h 75 g OGTT. Current volume of leisure-time physical activity (LTPA) was determined by self-reported questionnaires and expressed in metabolic equivalent hours (MET-h). Data on reimbursable diabetes medication from participants and non-participants was obtained from the register of the Finnish Social Insurance Institution. RESULTS: Compared with the controls, the former elite athletes had a significantly lower risk of type 2 diabetes (OR 0.72, 95% CI 0.53, 0.98). The risk of type 2 diabetes decreased with increased LTPA volume (OR 0.98, 95% CI 0.97, 0.99 per 1 MET-h/week). The former elite athletes also had a significantly lower risk of impaired glucose tolerance (IGT) than the controls (OR 0.58, 95% CI 0.38, 0.87). CONCLUSIONS/INTERPRETATION: A former career as an elite athlete protected from both type 2 diabetes and IGT in later life. In addition, the volume of current LTPA was inversely associated with the prevalence of type 2 diabetes.

The effect of structured exercise intervention on intensity and volume of total physical activity.

This study aimed to investigate the effects of a 12-week structured exercise intervention on total physical activity and its subcategories. Twenty-three overweight or obese middle aged men with impaired glucose regulation were randomized into a 12-week Nordic walking group, a power-type resistance training group, and a non-exercise control group. Physical activity was measured with questionnaires before the intervention (1-4 weeks) and during the intervention (1-12 weeks) and was expressed in metabolic equivalents of task. No significant change in the volume of total physical activity between or within the groups was observed (p > 0.050). The volume of total leisure-time physical activity (structured exercises + non-structured leisure-time physical activity) increased significantly in the Nordic walking group (p < 0.050) but not in the resistance training group (p > 0.050) compared to the control group. In both exercise groups increase in the weekly volume of total leisure-time physical activity was inversely associated with the volume of non-leisure-time physical activities. In conclusion, structured exercise intervention did not increase the volume of total physical activity. Albeit, endurance training can increase the volume of high intensity physical activities, however it is associated with compensatory decrease in lower intensity physical activities. To achieve effective personalized exercise program, individuality in compensatory behavior should be recognised. Key PointsStructured NW or RT training does not increase the volume of total physical activity.NW intervention can increase the volume of higher intensity activities.The increased in volume of LTPA induced by the structured NW and RT interventions was associated with the decreased volume of NLTPA.

Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women.

Background: To investigate associations between variations in the co-expression-based brain insulin receptor polygenic score and cardiometabolic risk factors and diabetes mellitus. Methods: This cross-sectional study included 1,573 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Cardiometabolic markers included body composition, waist circumference, circulating lipids, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 1 and 3 (IGFBP-1 and -3). Glucose and insulin levels were measured during a standardized 2-hour 75 g oral glucose tolerance test and impaired glucose regulation status was defined by the World Health Organization 2019 criteria. Analyzes were adjusted for population stratification, age, smoking, alcohol consumption, socioeconomic status, chronic diseases, birth weight, and leisure-time physical activity. Results: Multinomial logistic regression indicated that one standard deviation increase in hePRS-IR was associated with increased risk of diabetes mellitus in all participants (adjusted relative risk ratio, 1.17; 95% confidence interval, 1.01 to 1.35). In women, higher hePRS-IR was associated with greater waist circumference and higher body fat percentage, levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, insulin, and IGFBP-1 (all P≤0.02). The mePRS-IR was associated with decreased IGF-1 level in women (P=0.02). No associations were detected in men and studied outcomes. Conclusion: hePRS-IR is associated with sex-specific differences in cardiometabolic risk factor profiles including impaired glucose regulation, abnormal metabolic markers, and unfavorable body composition in women.

Social Mobility and Health-Related Quality of Life Trajectory Classes Among Older Women and Men.

OBJECTIVES: Changes in socioeconomic status (SES) during life may impact health in old age. We investigated whether social mobility and childhood and adulthood SES are associated with trajectories of health-related quality of life (HrQoL) over a 17-year period. METHODS: We used data from the Helsinki Birth Cohort Study (n = 2003, 46% men, mean age 61.5 years). Social mobility was derived from childhood SES, obtained from healthcare records, and register-based adulthood SES. RESULTS: Logistic regression models showed that lower adulthood SES was associated with lower physical HrQoL trajectories. Among men low (OR 3.95, p < .001), middle (OR 2.20, p = .006), and declining lifetime SES (OR 2.41, p = .001) were associated with lower physical HrQoL trajectories compared to men with high SES. Socioeconomic status was not associated with mental HrQoL trajectories. DISCUSSION: Declining SES during life course may have negative health consequences, while improving SES is potentially as beneficial as high SES to later-life health among men.

Body Composition in Late Midlife as a Predictor of Accelerated Age-associated Deficit-accumulation From Late Midlife into Old Age: A Longitudinal Birth Cohort Study.

BACKGROUND: Body mass index (BMI) may not be an optimal predictor of frailty as its constituents, lean and fat mass, may have opposite associations with frailty. METHODS: A linear mixed model analysis was performed in the Helsinki Birth Cohort Study (n = 2 000) spanning from 57 to 84 years. A 39-item frailty index (FI) was calculated on three occasions over 17 years. Body composition in late midlife included BMI, percent body fat (%BF), waist-to-hip ratio (WHR), lean mass index (LMI), and fat mass index (FMI). RESULTS: Mean FI levels increased by 0.28%/year among men and by 0.34%/year among women. Among women, per each kg/m2 higher BMI and each unit higher %BF the increases in FI levels per year were 0.013 percentage points (PP) steeper (95% CI = 0.004, 0.023) and 0.009 PP steeper (95% CI = 0.002, 0.016) from late midlife into old age. Among men, per each 0.1-unit greater WHR the increase in FI levels was 0.074 PP steeper per year (95% CI = -0.0004, 0.148). Cross-sectionally, greater FMI and LMI in late midlife were associated with higher FI levels but the direction of the association regarding LMI changed after adjustment for FMI. The categories "high FMI and high LMI" and "high FMI and low LMI" showed the highest FI levels relative to the category "low FMI and low LMI". CONCLUSIONS: In late midlife, greater adiposity (%BF) among women and abdominal obesity (WHR) among men may predispose to higher levels of frailty from late midlife into old age. Greater lean mass alone may be protective of frailty, but not in the presence of high fat mass.