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Background: Frailty is a complex, dynamic geriatric condition, but limited evidence has shown how genes and environment may contribute to its longitudinal changes. We sought to investigate sources of individual differences in the longitudinal trajectories of frailty, considering potential selection bias when including a sample of oldest-old twins., Methods: Data were from 2 Swedish twin cohort studies: a younger cohort comprising 1 842 adults aged 29-96 years followed up to 15 waves, and an older cohort comprising 654 adults aged ≥79 years followed up to 5 waves. Frailty was measured using the frailty index (FI). Age-based latent growth curve models were used to examine longitudinal trajectories, and extended to a biometric analysis to decompose variability into genetic and environmental etiologies., Results: A bilinear model with an inflection point at age 75 best described the data, indicating a fourfold to fivefold faster FI increase after 75 years. Twins from the older cohort had significantly higher mean FI at baseline but slower rate of increase afterward. FI level at age 75 was moderately heritable in both men (42%) and women (55%). Genetic influences were relatively stable across age for men and increasing for women, although the most salient amplification in FI variability after age 75 was due to individual-specific environmental influences for both men and women; conclusions were largely consistent when excluding the older cohort., Conclusion: Increased heterogeneity of frailty in late life is mainly attributable to environmental influences, highlighting the importance of targeting environmental risk factors to mitigate frailty in older adults., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Although frailty is commonly considered as a syndrome of old individuals, recent studies show that it can affect younger adults, too. Whether and how frailty differs in younger adults compared to old is however unknown. To this end, we analyzed the prevalence, characteristics, and risk factors of early-life (aged <65) and late-life (aged ≥65) frailty., Methods: We analyzed individuals in the UK Biobank (N = 405,123) and Swedish Screening Across the Lifespan Twin (SALT; N = 43,641) study. Frailty index (FI) scores ≥0.21 were used to demarcate frailty. Characteristics of early-life versus late-life frailty were analyzed by collating the FI items (deficits) into domains and comparing the domain scores between younger and older frail individuals. Logistic regression was used to assess the risk factors of frailty., Results: The pooled prevalence rates of frailty were 10.3% (95% confidence interval [CI]: 2.7-32.7), 14.4% (95% CI: 4.5-37.2), 19.2% (95% CI: 2.5-68.5) in individuals aged ≤55, 55-64, 65-74, respectively. Younger frail adults (aged <65) had higher scores in immunological, mental wellbeing, and pain-related domains, whereas older frail adults (aged ≥65) had higher scores in cardiometabolic, cancer, musculoskeletal, and sensory-related domains. Higher age, female sex, smoking, lower alcohol consumption, lower education, obesity, overweight, low income, and maternal smoking were similarly associated with the risk of early-life and late-life frailty., Conclusion: Frailty is prevalent also in younger age groups (aged <65) but differs in some of its characteristics from the old. The risk factors of frailty are nevertheless largely similar for early-life and late-life frailty., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: frailty shows an upward trajectory with age, and higher levels increase the risk of mortality. However, it is less known whether the shape of frailty trajectories differs by age at death or whether the rate of change in frailty is associated with mortality., Objectives: to assess population frailty trajectories by age at death and to analyse whether the current level of the frailty index (FI) i.e. the most recent measurement or the person-specific rate of change is more predictive of mortality., Methods: 3,689 individuals from three population-based cohorts with up to 15 repeated measurements of the Rockwood frailty index were analysed. The FI trajectories were assessed by stratifying the sample into four age-at-death groups: <70, 70-80, 80-90 and >90 years. Generalised survival models were used in the survival analysis., Results: the FI trajectories by age at death showed that those who died at <70 years had a steadily increasing trajectory throughout the 40 years before death, whereas those who died at the oldest ages only accrued deficits from age ~75 onwards. Higher level of FI was independently associated with increased risk of mortality (hazard ratio 1.68, 95% confidence interval 1.47-1.91), whereas the rate of change was no longer significant after accounting for the current FI level. The effect of the FI level did not weaken with time elapsed since the last measurement., Conclusions: Frailty trajectories differ as a function of age-at-death category. The current level of FI is a stronger marker for risk stratification than the rate of change., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association., Methods: The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41-97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment., Results: A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age., Conclusions: A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia., (© 2021. The Author(s).)

Background: The aim of this study was to develop a functional aging index (FAI) that taps four body systems: sensory (vision and hearing), pulmonary, strength (grip strength), and movement (gait speed) and to test the predictive value of FAI for entry into care and mortality., Method: Growth curve models and Cox regression models were applied to data from 1,695 individuals from three Swedish longitudinal studies of aging. Participants were aged 45-93 at intake and data from up to eight follow-up waves were available., Results: The rate of change in FAI was twice as fast after age 75 as before, women demonstrated higher mean FAI, but no sex differences in rates of change with chronological age were identified. FAI predicted entry into care and mortality, even when chronological age and a frailty index were included in the models. Hazard ratios indicated that FAI was a more important predictor of entry into care for men than women, whereas it was a stronger predictor of mortality for men than women., Conclusions: Measures of biological aging and functional aging differ in their predictive value for entry into care and mortality for men and women, suggesting that both are necessary for a complete picture of the aging process across genders., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antihypertensive, lipid‐lowering, and blood glucose‐lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow‐up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population‐based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self‐controlled analysis, where each individual is his/her own control, thereby adjusting for all time‐stable confounders. The analysis was additionally adjusted for time‐varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5–82.8 years at the first in‐person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid‐modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = −0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid‐modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes. [ABSTRACT FROM AUTHOR]