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.

Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study.

BACKGROUND: Common pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age. METHODS: We used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1-1.6 years), childhood (4.2-7.5 years); adolescence (12.0-16.0 years), and adulthood (22.0-67.8 years). RESULTS: Offspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of -0.89 standard deviation (SD) units for albumin with PTB (95% CI: -1.10 to -0.69, P=1.3×10-17) and -0.41 SD for total lipids in medium HDL with SGA (95% CI: -0.56 to -0.25, P=2.6×10-7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. -0.11 SD total fatty acids, 95% CI: -0.18 to -0.05, P=0.0009), and attenuating with older age across adulthood. CONCLUSIONS: These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

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.

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Physical and mental functioning trajectory classes among older adults and their association with specialized healthcare use.

BACKGROUND: Sex-specific physical and mental functioning trajectory classification could offer a way of understanding the differences in healthcare use at older age. METHODS: Using latent growth mixture models, sex-specific physical and mental functioning trajectory classes were formed for 1991 participants (mean age 61.5 years) of the Helsinki Birth Cohort Study. Physical and mental functioning were evaluated with the SF-36 survey conducted in clinical examinations in 2001-2004, 2011-2013, and 2017-2018. First and follow-up outpatient visits, emergency visits, and hospital days were extracted from a national register between the first clinical examination and the year 2017. We used regression models to examine the associations between healthcare use and trajectory classes. RESULTS: Two physical and mental functioning trajectory classes, high and intermediate, were observed for both sexes. The intermediate physical functioning trajectory class was associated with higher utilization rates of all examined specialized healthcare services (fully-adjusted IRRs varying 1.36-1.58; 95% CI = 1.03-1.79, 95% CI = 1.21-2.05) compared to the high trajectory class. Relative to the high trajectory class, the intermediate mental trajectory class was associated with the use of first outpatient visits (fully-adjusted IRRs 1.17, 95% CI = 1.03-1.33 for men, and 1.16, 95% CI = 1.04-1.30 for women). The findings were similar among both sexes. CONCLUSIONS: Compared to the high trajectory class, the intermediate physical functioning trajectory class was associated with greater specialized healthcare use and the intermediate mental trajectory class with first outpatient visits. Public health interventions should be considered to support functioning with aging.

Use of prescription benzodiazepines and related drugs in family caregivers: a nation-wide register-based study.

BACKGROUND: objective indicators of sleep and mental health problems in family caregivers have rarely been reported. OBJECTIVE: to study the use of prescription benzodiazepines and related drugs (BZDRD) in Finnish family caregivers and matched controls. DESIGN: prospective follow-up in 2012-17. SETTING: nationwide register-linkage study. SUBJECTS: all individuals who received family caregiver's allowance in Finland in 2012 (N = 42,256; mean age 67 years; 71% women) and controls matched for age, sex and municipality of residence (N = 83,618). METHODS: information on purchases of prescription BZDRD, including the number of defined daily doses (DDDs), between 2012 and 2017 was obtained from the Dispensations Reimbursable under the National Health Insurance Scheme register. Background information was obtained from national registers. RESULTS: more caregivers than controls used BZDRD, both among women (users per 100 person-years: 17.2 versus 15.2, P < 0.001) and men (14.6 versus 11.8, P < 0.001). These differences were largely explained by hypnotic BZDRD use. There were also more long-term BZDRD users per 100 person-years among caregivers than controls, both among women (5.0 versus 4.3, P = 0.001) and men (5.3 versus 3.8, P < 0.001). Use of hypnotic BZDRD in number of DDDs was higher in caregivers than in controls, particularly among men above 50 years. Caregivers used more anxiolytic BZDRD than controls from middle age to 75 years but less in the oldest age groups. CONCLUSIONS: higher level of BZDRD use among caregivers indicates that caregivers have more sleep and mental health problems than non-caregivers. Adequate treatment of these problems and support for caregiving should be ensured for caregivers.

The EU Child Cohort Network's core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables.

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.

Use of antidepressants among Finnish family caregivers: a nationwide register-based study.

PURPOSE: The purpose of this study was to compare the use of antidepressants over 6 years between family caregivers providing high-intensity care and a matched control population using register-based data. METHODS: The study includes all individuals, who received family caregiver's allowance in Finland in 2012 (n = 29,846 females, mean age 66 years; n = 12,410 males, mean age 71 years) and a control population matched for age, sex, and municipality of residence (n = 59,141 females; n = 24,477 males). Information on purchases of antidepressants, including the number of defined daily doses (DDD) purchased, between 2012 and 2017 was obtained from the national drugs reimbursement register. RESULTS: During the follow-up, 28.5% of female caregivers and 23.5% of the female controls used antidepressants, while the numbers for males were 21.1% and 16.4%, respectively. Adjusted for socioeconomic status, female caregivers used 43.7 (95% confidence interval 42.4-45.0) and their controls used 36.2 (35.3-37.2) DDDs of antidepressants per person-year. Male caregivers used 29.6 (27.6-31.6) and their controls used 21.6 (20.2-23.0) DDDs of antidepressants per person-year. Among female caregivers, the relative risk for use of antidepressants was similar (about 1.3) from 20 to 70 years, after which the relative risk declined. In male caregivers, the relative risk was highest (about 1.4-1.5) between 45 and 65 years. CONCLUSIONS: Family caregivers providing high-intensity care use more antidepressants and hence, are likely to have poorer mental health than the age-matched general population in virtually all age groups. However, the magnitude of the higher use varies as a function of age and gender.

Age-dependency in mortality of family caregivers: a nationwide register-based study.

BACKGROUND: Evidence on family caregivers' health is conflicting. AIM: To investigate all-cause and cause-specific mortality in Finnish family caregivers providing high-intensity care and to assess whether age modifies the association between family caregiver status and mortality using data from multiple national registers. METHODS: The data include all individuals, who received family caregiver's allowance in Finland in 2012 (n = 42,256, mean age 67 years, 71% women) and a control population matched for age, sex, and municipality of residence (n = 83,618). Information on dates and causes of death between 2012 and 2017 were obtained from the Finnish Causes of Death Register. RESULTS: Family caregivers had lower all-cause mortality than the controls over the follow-up (8.1 vs. 11.6%) both among women (socioeconomic status adjusted hazard ratio [HR]: 0.64, 95% CI 0.61-0.68) and men (adjusted HR: 0.73, 95% CI 0.70-0.77). When modelling all-cause mortality as a function of age, younger caregivers had only slightly lower or equal mortality to their controls, but older caregivers had markedly lower mortality than their controls, up to more than 10% lower. Caregivers had a lower mortality rate for all the causes of death studied, namely cardiovascular, cancer, neurological, external, respiratory, gastrointestinal and dementia. The lowest risk was for dementia (subhazard ratio = 0.29, 95% CI 0.25-0.34). CONCLUSIONS: Older family caregivers had lower mortality than the age-matched general population while mortality did not differ according to caregiver status in young adulthood. This age-dependent advantage in mortality is likely to reflect the selection of healthier individuals into the family caregiver role.

The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents.

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.

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.

Hearing in Real-Life Environments (HERE): Structure and Reliability of a Questionnaire on Perceived Hearing for Older Adults.

OBJECTIVES: The ability to hear in a variety of social situations and environments is vital for social participation and a high quality of life. One way to assess hearing ability is by means of self-report questionnaire. For questionnaires to be useful, their measurement properties, based on careful validation, have to be known. Only recently has consensus been reached concerning how to perform such validation and been published as COSMIN (consensus-based standards for the selection of health status measurement instruments) guidelines. Here the authors use these guidelines to evaluate the measurement properties of the "Hearing in Real-Life Environments" (HERE) questionnaire, a newly developed self-report measure that assesses speech perception, spatial orientation, and the social-emotional consequences of hearing impairment in older adults. The aim is to illustrate the process of validation and encourage similar examinations of other frequently used questionnaires. DESIGN: The HERE questionnaire includes 15 items with a numeric rating scale from 0 to 10 for each item and allows the assessment of hearing with and without hearing aids. The evaluation was performed in two cohorts of community-dwelling older adults from Finland (n = 581, mean 82 years) and the United Kingdom (n = 50, mean 69 years). The internal structure of the questionnaire and its relationship to age, hearing level, and self-reported and behavioral measures of speech perception was assessed and, when possible, compared between cohorts. RESULTS: The results of the factor analysis showed that the HERE's internal structure was similar across cohorts. In both cohorts, the factor analysis showed a satisfactory solution for three factors (speech hearing, spatial hearing, and socio-emotional consequences), with a high internal consistency for each factor (Cronbach's α's for the factors from 0.90 to 0.97). Test-retest analysis showed the HERE overall mean score to be stable and highly replicable over time (intraclass correlation coefficient = 0.86, standard error of measurement of the test score = 0.92). The HERE overall mean score correlated highly with another self-report measure of speech perception, the Speech Spatial Qualities of Hearing questionnaire (standardized regression coefficient [ß] = -0.75, p < 0.001), moderately highly with behaviorally assessed hearing level (best-ear average: ß = 0.45 to 0.46), and moderately highly with behaviorally measured intelligibility of sentences in noise (ß = -0.50, p < 0.001). CONCLUSIONS: Using the COSMIN guidelines, the authors show that the HERE is a valid, reliable, and stable questionnaire for the assessment of self-reported speech perception, sound localization, and the socio-emotional consequences of hearing impairment in the context of social functioning. The authors also show that cross-cultural data collected using different data collection strategies can be combined with a range of statistical methods to validate a questionnaire.

Hearing loss and use of health services: a population-based cross-sectional study among Finnish older adults.

BACKGROUND: Older adults with hearing difficulties face problems of communication which may lead to underuse of health services. This study investigated the association of hearing loss and self-reported hearing difficulty with the use of health services and unmet health care needs in older adults. METHODS: Data on persons aged 65 and older (n = 2144) drawn from a population-based study, Health 2000, were analyzed. Hearing loss was determined with screening audiometry (n = 1680). Structured face-to-face interviews were used to assess self-reported hearing difficulty (n = 1962), use of health services (physician and nurse visits, health examinations, mental health services, physical therapy, health promotion groups, vision test, hearing test, mammography, PSA test) and perceived unmet health care needs. Multivariable logistic regression analyses were used. RESULTS: After adjusting for socio-economic and health-related confounders, persons with hearing loss (hearing level of better ear 0.5-2 kHz > 40 dB) were more likely to have used mental health services than those with non-impaired hearing (OR = 3.2, 95 % CI 1.3-7.9). Self-reported hearing difficulty was also associated with higher odds for mental health service use (OR = 2.1 95 % CI 1.2-3.5). Hearing was not associated with use of the other health services studied, except presenting for a hearing test. Persons with self-reported hearing difficulty were more likely to perceive unmet health care needs than those without hearing difficulty (OR = 1.7, 95 % CI 1.4-2.1). CONCLUSIONS: Older adults with hearing loss or self-reported hearing difficulty are as likely to use most health services as those without hearing loss. However, self-reported hearing difficulty is associated with experiencing unmet health care needs. Adequate health services should be ensured for older adults with hearing difficulties.

Self-reported hearing is associated with time spent out-of-home and withdrawal from leisure activities in older community-dwelling adults.

BACKGROUND: Hearing difficulties are prevalent among older people and can lead to difficulties in social interaction. These difficulties may increase the tendency to remain at home and withdraw from leisure activities. AIMS: To investigate whether self-reported hearing problems are associated with time spent out-of-home and withdrawal from a leisure activity among older persons. METHODS: Cross-sectional and longitudinal data on 75- to 90-year-old community-dwelling men and women (n = 767) was used. Self-reports of hearing, diseases, and difficulty walking 2 km were obtained via home interviews at baseline, and withdrawal from a leisure activity via 1- and 2-year follow-up telephone interviews. Time spent out-of-home was obtained from a subsample (n = 532) via seven-day diaries at baseline. RESULTS: Hearing problems were associated with time spent out-of-home (p = 0.025) and withdrawal from a leisure activity (p = 0.025) among persons reporting no walking difficulty, but not among those reporting walking difficulty (p = 0.269 and 0.396, respectively). Among the former, persons with major hearing problems spent significantly less time out-of-home (estimated marginal mean 161 min, 95 % CI 122-212) than those with good hearing (242, 95 % CI 218-270). Persons with major hearing problems also had 3.0 times higher odds (95 % CI 1.3-7.1) for withdrawal from a leisure activity than persons with good hearing during the two-year follow-up. DISCUSSION AND CONCLUSIONS: Among older adults without walking difficulty, hearing problems may reduce time spent out-of-home and increase the likelihood for withdrawal from a leisure activity. Decreased leisure and out-of-home activity may have negative effects on older persons' social, mental and physical functioning.

Associations of disordered sleep with body fat distribution, physical activity and diet among overweight middle-aged men.

This cross-sectional study aimed to investigate whether body fat distribution, physical activity levels and dietary intakes are associated with insomnia and/or obstructive sleep apnea among overweight middle-aged men. Participants were 211 Finnish men aged 30-65 years. Among the 163 overweight or obese participants, 40 had insomnia only, 23 had obstructive sleep apnea only, 24 had comorbid insomnia and obstructive sleep apnea and 76 were without sleep disorder. The remaining 48 participants had normal weight without sleep disorder. Fat mass, levels of physical activity and diet were assessed by dual-energy X-ray densitometry, physical activity questionnaire and 3-day food diary, respectively. Among the overweight participants, we found that: (i) groups with sleep disorders had higher fat mass in trunk and android regions than the group without sleep disorder (P = 0.048-0.004); (ii) the insomnia-only group showed a lower level of leisure-time physical activity (436.9 versus 986.5 MET min week(-1) , P = 0.009) and higher intake of saturated fatty acids (14.8 versus 12.7 E%, P = 0.011) than the group without sleep disorder; and (iii) the comorbid group had a lower level of leisure-time physical activity (344.4 versus 986.5 MET min week(-1) , P = 0.007) and lower folate intake (118.9 versus 152.1 µg, P = 0.002) than the group without sleep disorder, which were independent of body mass index. The results suggest that central obesity is associated with insomnia and/or obstructive sleep apnea. In addition, low levels of leisure-time physical activity and poor dietary intakes are related to insomnia or comorbid insomnia and obstructive sleep apnea among overweight men.

Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

Self-reported hearing difficulties and changes in life-space mobility among community-dwelling older adults: a Two-year follow-Up study.

BACKGROUND: Life-space mobility reflects individuals' actual mobility and engagement with society. Difficulty in hearing is common among older adults and can complicate participation in everyday activities, thus restricting life-space mobility. The aim of this study was to examine whether self-reported hearing predicts changes in life-space mobility among older adults. METHODS: We conducted a prospective cohort study of community-dwelling older adults aged 75-90 years (n = 848). At-home face-to-face interviews at baseline and telephone follow-up were used. Participants responded to standardized questions on perceived hearing at baseline. Life-space mobility (the University of Alabama at Birmingham Life-Space Assessment, LSA, range 0-120) was assessed at baseline and one and two years thereafter. Generalized estimating equations were used to analyze the effect of hearing difficulties on changes in LSA scores. RESULTS: At baseline, participants with major hearing difficulties had a significantly lower life-space mobility score than those without hearing difficulties (mean 54, 95 % CI 50-58 vs. 57, 95 % CI 53-61, p = .040). Over the 2-year follow-up, the life-space mobility score declined in all hearing categories in a similar rate (main effect of time p < .001, group x time p = .164). Participants with mild or major hearing difficulties at baseline had significantly higher odds for restricted life-space (LSA score < 60) at two years (OR 1.8, 95 % CI 1.0-3.2 and 2.0, 95 % CI 1.0-3.9, respectively) compared to those without hearing difficulties. The analyses were adjusted for chronic conditions, age, sex and cognitive functioning. CONCLUSIONS: People with major hearing difficulties had lower life-space mobility scores at baseline but did not exhibit accelerated decline over the follow-up compared to those without hearing difficulties. Life-space mobility describes older people's possibilities for participating in out-of-home activities and access to community amenities, which are important building blocks of quality of life in old age. Early recognition of hearing difficulties may help prevent life-space restriction.

Life-space mobility and dimensions of depressive symptoms among community-dwelling older adults.

OBJECTIVES: To examine the association between life-space mobility and different dimensions of depressive symptoms among older community-dwelling people. METHODS: Cross-sectional analyses of baseline data of the 'Life-Space Mobility in Old Age' cohort study were carried out. The participants were community-dwelling women and men aged 75-90 years (N = 848). Data were gathered via structured interviews in participants' home. Life-space mobility (the University of Alabama at Birmingham (UAB) Life-Space Assessment - questionnaire) and depressive symptoms (Centre for Epidemiological Studies Depression Scale, CES-D) were assessed. Other factors examined included sociodemographic factors, difficulties walking 500 m, number of chronic diseases and the sense of autonomy in participation outdoors (subscale of Impact on Participation and Autonomy questionnaire). RESULTS: Poorer life-space mobility was associated with higher prevalence of different dimensions of depressive symptoms. The associations were partially mediated through walking difficulties, health and the sense of autonomy in participation outdoor activities. CONCLUSION: Poorer life-space mobility interrelates with higher probability for depressive symptoms, thus compromising older adults' mental wellbeing. A focus on older adults' life-space mobility may assist early identification of persons, who have elevated risk for depressive symptoms. The association between life-space mobility and depressive symptoms should be studied further utilizing longitudinal study designs to examine temporality and potential causality.

Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course: a longitudinal birth cohort study.

BACKGROUND: Early growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age. METHODS: In this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42-53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods. FINDINGS: From Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51·9%] men and 5625 [48·1%] women) were included in the study. Individuals born to mothers younger than 25 years (ß 0·09; 95% CI 0·06-0·12), mothers with a BMI of 25-30 kg/m2 (0·08; 0·05-0·10), and mothers with a BMI more than 30 kg/m2 (0·26; 0·21-0·31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25-30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2·5 kg (0·17; 0·10-0·25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0·27; 0·23-0·30) and wartime parental separation (0·24; 0·19-0·29 for boys; 0·31; 0·25-0·36 for girls) were associated with a faster rate of chronic disease accumulation. INTERPRETATION: Our findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status. FUNDING: Finska Läkaresällskapet, Liv och Hälsa rf, the Finnish Pediatric Research Foundation, and Folkhälsan Research Center. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.