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.

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 participants 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.

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.

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.

Frailty in Late Midlife to Old Age and Its Relationship to Medical Imaging Use and Imaging-related Costs: A Longitudinal Study.

Background Frailty, defined as an increased vulnerability to and impaired recovery from stressors, is common in individuals in late midlife to old age. While frailty predisposes individuals to adverse health outcomes and increased health care utilization, how it impacts imaging service use and related costs remains unclear. Purpose To determine whether frailty is associated with greater use of imaging services and higher imaging-related costs. Materials and Methods This longitudinal study included a subset of participants from the Helsinki Birth Cohort Study who were clinically assessed up to three times from late midlife to old age between August 2001 and September 2018. A frailty index (FI) based on 41 variables was calculated, and an FI of 0.25 or more indicated frailty. Associations of baseline frailty and its rate of change during the study with medical imaging service use and imaging-related costs were assessed using covariate-adjusted negative binomial and other generalized linear models. Results Of the 1995 participants (mean age, 61.5 years ± 2.9 [SD]; 1074 female participants) included in this study, 569 (28.5%) were identified as frail at baseline, and these participants underwent 10 677 (42.4%) of the 25 172 medical imaging examinations among the participants. Compared to participants who were not frail at baseline, participants who were frail at baseline showed increased use of all imaging modalities (incidence rate ratio [IRR], 2.28 [95% CI: 1.97, 2.64]; P < .001) and higher imaging costs (log annual cost, 3.26 [95% CI: 2.36, 4.50]; P < .001). Compared to participants with stable or slow change in frailty (<0.0010 FI units per year), participants with a rapid increase in frailty (>0.0064 FI units per year) from late midlife to old age showed greater use of all medical imaging services, independent of FI at baseline (IRR, 1.82 [95% CI: 1.53, 2.17]; P < .001) and had higher imaging costs (log annual cost, 1.62 [95% CI: 1.30, 2.01)]; P < .001). Conclusion The presence of frailty and its progression rate are associated with increased use of imaging services and higher imaging-related costs. © RSNA, 2023 Supplemental material is available for this article.

Midlife cardiovascular health factors as predictors of retirement age, work-loss years, and years spent in retirement among older businessmen.

Cardiovascular disease (CVD) is one of the leading causes of premature retirement. However, the relationship between CVD risk factors and workforce participation is not well known. We studied the relationship between midlife CVD risk, age at retirement, work-loss years, and survival in retirement. Middle-aged Finnish men (initial n = 3490, mean age = 47.8 years) were assessed for CVD risk factors and general health in the 1970s. They worked as business executives and provided information on their retirement status in the year 2000. Survival was followed up to the 9th decade of life with a follow-up of up to 44 years. Work-loss years were calculated as death or retirement occurring at age ≤ 65 years. Smoking, body mass index, and alcohol use were used as covariates, excluding models of CVD risk, which were adjusted for alcohol use only. Higher risk of 10-year fatal CVD was associated with 0.32 more years (relative risk < 1 vs. 1, covariate-adjusted ß = 0.32, 95% CI = 0.13, 0.53) of work-loss. Higher risk of 5-year incident (covariate-adjusted time-constant HR = 1.32, 95% CI = 1.19, 1.47) and 10-year fatal (covariate-adjusted time-dependent HR = 1.55, 95% CI = 1.30, 1.85) CVD in midlife were associated with fewer years spent in retirement. Poorer self-rated health and physical fitness and higher levels of triglycerides were associated with increased hazard of earlier retirement, more work-loss years, and fewer years spent in retirement. Poorer health and greater midlife CVD risk may be associated with earlier exit from the workforce and fewer years spent in retirement. Management of CVD risk in midlife may support people to work longer.

Healthy ageing from birth to age 84 years in the Helsinki Birth Cohort Study, Finland: a longitudinal study.

BACKGROUND: The true prevalence of healthy ageing on a population level is unknown. In this study we aimed to examine the upper limit for the prevalence of healthy ageing, by quantifying the probability of surviving and remaining free of chronic diseases that could impact functioning (ie, healthy survival) across adulthood. We also estimated the prevalence of clinically assessed healthy ageing, and the determinants of healthy survival and healthy ageing. METHODS: In this longitudinal study, we assessed men and women born in 1934-44 from the Helsinki Birth Cohort Study (Helsinki, Finland; n=13 140). We obtained information on chronic diseases, deaths, and early-to-midlife variables from national registers, databases, and health records for the period Jan 1, 1971, to Dec 31, 2017 (follow-up 951 088 person-years). We also collated data from clinical visits conducted in 2001-04 and 2017-18. Healthy ageing was defined on the basis of clinical data according to six criteria covering chronic diseases, cognitive function, physical performance, depressive symptoms, pain interference, and social functioning. We analysed the probability of healthy survival across adulthood using the Kaplan-Meier method, and the determinants of healthy survival using Cox regression models. We assessed the association of healthy ageing status in 2017-18 (n=813 with available data) with late-midlife factors collected in 2001-04 using age-adjusted logistic regression. FINDINGS: The probability of healthy survival was 42·8% (95% CI 41·6-44·0) in men and 40·1% (38·9-41·4) in women at age 65 years, and 22·5% (21·5-23·6%) in men and 24·4% (23·3-25·6) in women at age 75 years. Healthy survival was associated with socioeconomic position in childhood (adjusted hazard ratio [aHR], upper-middle class vs manual worker, men: 1·21 [1·11-1·31]; women: 1·15 [95% CI 1·05-1·26]) and years of education (aHR per 1 SD increase, men: 1·12 [1·08-1·16]; women: 1·03 [1·00-1·07]). In men, healthy survival was also associated with lower maternal BMI in late pregnancy (aHR per 1 SD increase 0·93 [0·90-0·96]), and in women, with shorter height at age 7 years (aHR per 1 SD increase 0·95 [0·91-0·99]). Among the 813 individuals with relevant clinical assessment data, 159 (19·6%) met all six criteria for healthy ageing at mean age 76 years (SD 3). In addition to age, we found that nutrition (Alternative Healthy Eating Index, age-adjusted odds ratio [aOR] per 1 point increase 1·03 [1·01-1·05]), former smoker status (vs non-smoker status, aOR 0·68 [0·47-0·98], and use of lipid-lowering medication (vs not used, aOR 0·60 [0·42-0·87]) in late midlife (mean age 61 years [SD 3]) were associated with healthy ageing. INTERPRETATION: The probability of healthy survival, as the upper limit for healthy ageing, was less than 50% from age 65 years. The probability of healthy survival and healthy ageing was influenced by several factors across the life course. Promotion of healthy ageing needs to take a life course approach. FUNDING: Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, European Commission Seventh Framework Programme, EU Horizon 2020, and the Academy of Finland.

Association between resilience and frailty in older age: Findings from the Helsinki Birth Cohort Study.

OBJECTIVES: Resilience, a capacity to cope with adversity, has been linked to better functioning and health in older age. However, little is still known about resilience in relation to frailty. We explored whether resilience would be associated with frailty in older age and if we would observe differences in association between resilience and frailty according to the type of adversity. METHODS: The study included 681 participants from the Helsinki Birth Cohort Study, born in Helsinki between 1934 and 1944. Adversities in older age and resilience were assessed between 2015 and 2018 with the Hardy-Gill resilience scale, scores ranging from 0 (low) to 18 (high resilience). Frailty was assessed in 2017-18 by using a deficit accumulation-based Frailty Index with a scale from 0 to 1. Adversities were coded into categories by using a data-driven approach. A linear regression analysis was used to explore the association between resilience and frailty. RESULTS: Resilience was inversely associated with frailty in older age (ß -0.009, 95% CI -0.011 to -0.007, p<0.001). The association was observed for all other type of adversities except adversity in relationships and economical adversity. DISCUSSION: A higher resilience was related to lower levels of frailty in older age. Differences in association between resilience and frailty were observed according to the type of adversity. Focusing on the type of adverse events and the capacity to "bounce back" after an adversity in older age may reveal new perspectives on how to prevent and postpone frailty.

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.

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.

Retirement as a predictor of physical functioning trajectories among older businessmen.

BACKGROUND: Associations between retirement characteristics and consequent physical functioning (PF) are poorly understood, particularly in higher socioeconomic groups, where postponing retirement has had both positive and negative implications for PF. METHODS: Multiple assessments of PF, the first of which at the mean age of 73.3 years, were performed on 1709 men who were retired business executives and managers, using the RAND-36/SF-36 instrument, between 2000 and 2010. Questionnaire data on retirement age and type of pension was gathered in 2000. Five distinct PF trajectories were created using latent growth mixture modelling. Mortality- and covariate-adjusted multinomial regression models were used to estimate multinomial Odds Ratios (mOR) on the association between retirement characteristics and PF trajectories. RESULTS: A one-year increase in retirement age was associated with decreased likelihood of being classified in the 'consistently low' (fully adjusted mOR = 0.82; 95%CI = 0.70, 0.97; P = 0.007), 'intermediate and declining' (mOR = 0.89; 95%CI = 0.83, 0.96; P = 0.002), and 'high and declining' (mOR = 0.92; 95%CI = 0.87, 0.98; P = 0.006) trajectories, relative to the 'intact' PF trajectory. Compared to old age pensioners, disability pensioners were more likely to be classified in the 'consistently low' (mOR = 23.77; 95% CI 2.13, 265.04; P = 0.010), 'intermediate and declining' (mOR = 8.24; 95%CI = 2.58, 26.35; P < 0.001), and 'high and declining' (mOR = 2.71; 95%CI = 1.17, 6.28; P = 0.020) PF trajectories, relative to the 'intact' PF trajectory. CONCLUSIONS: Among executives and managers, older age at retirement was associated with better trajectories of PF in old age. Compared to old age pensioners, those transitioning into disability and early old age pensions were at risk of having consistently lower PF in old age.

Early-Life Factors as Predictors of Age-Associated Deficit Accumulation Across 17 Years From Midlife Into Old Age.

BACKGROUND: Early-life exposures have been associated with the risk of frailty in old age. We investigated whether early-life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age. METHODS: A linear mixed model analysis was performed using data from 3 measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n = 2 000) aged 57-84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early-life stress (wartime separation from both parents) was obtained from registers and health care records. RESULTS: At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34%/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1 kg greater birth weight the increase in FI levels per year was -0.087 percentage points slower (95% confidence interval = -0.163, -0.011; p = 0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change. CONCLUSIONS: Early-life factors seem to contribute to disparities in frailty from midlife into old age. Early-life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.

The utilization of primary healthcare services among frail older adults - findings from the Helsinki Birth Cohort Study.

BACKGROUND: The impact of frailty on primary healthcare service use, especially general practice office visits and remote contacts, is currently unknown. Further, little is known about the association of frailty with physiotherapy contacts. METHODS: We examined the utilization of primary healthcare services among 1064 participants from the Helsinki Birth Cohort Study between the years 2013 and 2017. Frailty was assessed based on Fried's frailty criteria at mean age of 71.0 (2.7 SD) years in clinical examinations between the years 2011 and 2013. General practice office visits and remote contacts, the total number of general practice contacts, physiotherapy contacts, and the total number of primary healthcare contacts were extracted from a national Finnish register. We analyzed the data with negative binomial regression models. RESULTS: Of the 1064 participants, 37 were frail (3.5%) and 427 pre-frail (40.1%); 600 non-frail (56.4%) served as a reference group. Frailty was associated with general practice office visits (IRR 1.31, 95% CI=1.01-1.69), physiotherapy contacts (IRR 2.97, 95% CI=1.49-5.91) and the total number of primary healthcare contacts (IRR 1.41, 95% CI=1.07-1.85). Pre-frailty predicted the use of general practice remote contacts (IRR 1.39, 95% CI=1.22-1.57) and the total number of general practice contacts (IRR 1.25, 95% CI=1.12-1.40). CONCLUSIONS: Frailty increases the overall primary healthcare service use whereas pre-frailty is associated with the use of general practice services, especially remote contacts. Primary healthcare needs measures to adapt healthcare services based on the needs of rapidly increasing number of pre-frail and frail older adults and should consider preventative interventions against frailty.

The utilization of specialized healthcare services among frail older adults in the Helsinki Birth Cohort Study.

BACKGROUND: The association between frailty and specialized healthcare utilization is not well studied. We, therefore, examined the utilization of specialized healthcare services among frail Finnish older adults. METHODS: A sub-sample of 1060 participants of the Helsinki Birth Cohort Study were followed prospectively for specialized healthcare utilization from nationwide registers between the years 2013 and 2017. The participants' frailty status was assessed according to Fried's criteria at a mean age of 71.0 (2.7 SD) years between the years 2011 and 2013. A negative binomial regression model was used to examine the association between frailty and the total number of visits, emergency visits, outpatient appointments separating the first outpatient appointments and the follow-up appointments, inpatient care including elective and non-elective hospital admissions and the total number of hospital days. We also calculated average length of stay (ALOS) and used the Kruskal-Wallis test to examine the differences between the groups. RESULTS: After adjusting for covariates, frailty was significantly associated with the number of specialized healthcare visits (IRR 1.50, 95% CI = 1.04-2.15) and all subgroups of visits apart from follow-up outpatient appointments. Frailty was particularly strongly associated with the number of hospital days (IRR 5.24, 95% CI = 2.35-11.7) and notably with emergency visits (IRR = 2.26, 95% CI = 1.45-3.51) and hospital admissions (IRR 2.23, 95% CI = 1.39-3.56). Frail older adults had also higher ALOS compared to non-frail participants (p = .009). CONCLUSIONS: Frailty increases the use of most specialized healthcare services. Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems.KEY MESSAGEFrailty is associated with the utilization of most specialized healthcare services, the most expensive part of the healthcare in most high-income countries.The association of frailty with inpatient care is particularly strong.Preventative interventions against frailty are needed to decrease the burden on specialized healthcare systems.

Retirement age and type as predictors of frailty: a retrospective cohort study of older businessmen.

OBJECTIVES: To study the association between retirement characteristics and frailty in a homogenous population of former business executives. DESIGN: Cross-sectional cohort study using data from the Helsinki Businessmen Study. SETTING: Helsinki, Finland. PARTICIPANTS: 1324 Caucasian men, born in 1919-1934, who had worked as business executives and managers and of whom 95.9% had retired by the year 2000. Questions on age at and type of retirement, lifestyle and chronic conditions were embedded in questionnaires. PRIMARY AND SECONDARY OUTCOME MEASURES: Frailty assessed according to a modified phenotype definition at mean age 73.3 years. RESULTS: Mean age at retirement was 61.3 years (SD 4.3) and 37.1% had retired due to old age. The prevalence of frailty was lowest among men retiring at ages 66-67 years but increased among those who worked up to age 70 years or older. Compared with men who retired before age 55 years, those retiring at ages 58-69 years were at decreased risk of frailty in old age relative to non-frailty (adjusted ORs 0.07-0.29, p<0.05). Compared with men who transitioned into old age retirement, those who retired due to disability were at increased risk of prefrailty (adjusted OR 1.53, 95% CI 1.01 to 2.32) and frailty (adjusted OR 3.52, 95% CI 1.97 to 6.29), relative to non-frailty. CONCLUSION: Exiting working life early and continuing to be occupationally active until age 70 years and older were both associated with increased risk of frailty among the men. Promotion of longer work careers could, however, promote healthier ageing, as the lowest prevalence of frailty was observed in former business executives who retired at ages 66-67 years.

Body size at birth and age-related macular degeneration in old age.

PURPOSE: To study associations between body size at birth and age-related macular degeneration (AMD) in old age. METHODS: The study sample consists of 1497 community-dwelling individuals (56.1% women) aged 67-89 years with birth data and retinal data collected twice in old age 5 years apart. Birth data (weight, length, birth order) were extracted from original birth records. Digital retinal photographs were graded to determine AMD status. Data on covariates were collected at the baseline physical examination in old age. Multivariable regression analyses were used to study the association between birth data and AMD adjusting for known confounding factors, including birth year cohort effects. RESULTS: The prevalence and 5-year incidence of any AMD were 33.1% and 17.0%, respectively. Men and women born in 1930-1936 were significantly leaner and slightly longer at birth compared to those in earlier birth cohorts. There were no consistent associations between weight, length or ponderal index (PI) at birth and AMD in old age even when stratified by birth cohort. Age-related macular degeneration (AMD) prevalence (39.8%) and 5-year incidence (28.6%) were highest in individuals who were in the highest quartile of PI at birth and who were obese in old age. CONCLUSION: Body size at birth was not consistently associated with AMD in old age, suggesting that intrauterine growth might have little direct importance in the development of AMD in old age. It is possible that some yet unknown factors related to larger size at birth and obesity in old age may explain differences in the prevalence and incidence of AMD in the ageing population.

Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

Midlife Cardiovascular Status and Old Age Physical Functioning Trajectories in Older Businessmen.

OBJECTIVES: The associations between cardiovascular disease (CVD) risk and later physical functioning have been observed, but only a few studies with follow-up into old age are available. We investigated the association between cardiovascular status in midlife and physical functioning trajectories in old age. DESIGN: Prospective cohort study. SETTING: Helsinki Businessmen Study. PARTICIPANTS: We studied white men born between 1919 and 1934 in the Helsinki Businessmen Study (HBS, initial n = 3490). MEASUREMENTS: Three CVD status groups were formed based on clinical measurements carried out in 1974: signs of CVD (diagnosed clinically or with changes in ECG, chronic disease present or used medication, n = 563); healthy and low CVD risk (n = 593) and high CVD risk (n = 1222). Of them, 1560 men had data on physical functioning from at least one of four data collection waves between 2000-2010. Ten questions from the RAND-36 (SF-36) survey were used to construct physical functioning trajectories with latent class growth mixture models. Mortality was accounted for in competing risk models. RESULTS: A five-class solution provided the optimal number of trajectories: "intact," "high stable," "high and declining," "intermediate and declining," and "consistently low" functioning. Compared with low CVD risk, high CVD risk in midlife decreased the risk of being classified into the intact (fully adjusted ß = -3.98; standard error = 2.0; P = .046) relative to the consistently low physical functioning trajectory. Compared with low CVD risk, those with signs of CVD were less likely to follow the intact, high stable, or high and declining relative to the consistently low trajectory (all P < .018). CONCLUSION: Among businessmen, a more favorable CVD profile in midlife was associated with better development of physical functioning in old age. J Am Geriatr Soc 67:2490-2496, 2019.

Telomere Length and Frailty: The Helsinki Birth Cohort Study.

OBJECTIVES: Telomere length is associated with aging-related pathologies. Although the association between telomere length and frailty has been studied previously, only a few studies assessing longitudinal changes in telomere length and frailty exist. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: A subpopulation of the Helsinki Birth Cohort Study consisting of 1078 older adults aged 67 to 79 years born in Helsinki, Finland, between 1934 and 1944. MEASURES: Relative leukocyte telomere length (LTL) was measured using quantitative real-time polymerase chain reaction at the average ages of 61 and 71 years, and at the latter the participants were assessed for frailty according to Fried criteria. RESULTS: The mean ± SD relative LTLs were 1.40 ± 0.29 (average age 61 years) and 0.86 ± 0.30 (average age 71 years) for the cohort. A trend of shorter mean relative LTL across frailty groups was observed at 61 years (P = .016) and at 71 years (P = .057). Relative LTL at age 61 years was significantly associated with frailty: per 1-unit increase in relative LTL, the corresponding relative risk ratio (RRR) of frailty was 0.28 (95% confidence interval [CI] 0.08-0.97), adjusting for several confounders. Also, LTL at age 71 years was associated with frailty (RRR 0.18, 95% CI 0.04-0.81) after adjustment for sex, age, and adult socioeconomic status, but further adjustment attenuated the association. No associations between telomere shortening and frailty were observed during the 10-year follow-up. CONCLUSIONS: Shorter relative LTL was associated with frailty in cross-sectional and longitudinal analyses, but telomere shortening was not, suggesting that short LTL may be a biomarker of frailty.