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.

Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. MATERIALS AND METHODS: Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). RESULTS: The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. DISCUSSION: Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.

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.

Epigenome-wide analysis of frailty: Results from two European twin cohorts.

Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.

Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life.

Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for chronological age, sex, education, and smoking. We assessed curvilinear associations of BMI and chronological age with physiological age, and interactions between BMI, MetS, and chronological age. We found a significant three-way interaction between BMI, MetS, and chronological age on FI (p-interaction = 0·006), not FAI. Consequently, we stratified FI analyses by age: < 65, 65-85, and ≥ 85 years, and modeled FAI across ages. Except for FI at ages ≥ 85, BMI had U-shaped associations with FI and FAI, where BMI around 26-28 kg/m2 was associated with the lowest physiological age. MetS was associated with higher FI and FAI, except for FI at ages < 65, and modified the BMI-FI association at ages 65-85 (p-interaction = 0·02), whereby the association between higher BMI levels and FI was stronger in individuals with MetS. Age modified the MetS-FI association in ages ≥ 85, such that it was stronger at higher ages (p-interaction = 0·01). Low BMI, high BMI, and metabolic syndrome were associated with higher physiological age, contributing to overall health status among older individuals and potentially accelerating aging.

Use of Electronic Medical Records (EMR) in Gerontology: Benefits, Considerations and a Promising Future.

Electronic medical records (EMRs) have many benefits in clinical research in gerontology, enabling data analysis, development of prognostic tools and disease risk prediction. EMRs also offer a range of advantages in clinical practice, such as comprehensive medical records, streamlined communication with healthcare providers, remote data access, and rapid retrieval of test results, ultimately leading to increased efficiency, enhanced patient safety, and improved quality of care in gerontology, which includes benefits like reduced medication use and better patient history taking and physical examination assessments. The use of artificial intelligence (AI) and machine learning (ML) approaches on EMRs can further improve disease diagnosis, symptom classification, and support clinical decision-making. However, there are also challenges related to data quality, data entry errors, as well as the ethics and safety of using AI in healthcare. This article discusses the future of EMRs in gerontology and the application of AI and ML in clinical research. Ethical and legal issues surrounding data sharing and the need for healthcare professionals to critically evaluate and integrate these technologies are also emphasized. The article concludes by discussing the challenges related to the use of EMRs in research as well as in their primary intended use, the daily clinical practice.

Anticoagulant treatment and COVID-19 mortality among older adults living in nursing homes in Sweden.

Background: Anticoagulants (AC) were introduced in March 2020 as standard of care in nursing home (NH) residents affected with COVID-19 in the Stockholm region, Sweden. ACs are proven to reduce the risk of complications and mortality from COVID-19 among patients of other ages and settings, but there is limited scientific evidence underpinning this practice in the NH setting. Methods: This matched cohort study included 182 NH residents in the Stockholm Region diagnosed with COVID-19 in March-May 2020. The main exposure was any AC treatment. Exposed (n = 91), 49% prevalent (pre-COVID-19 diagnosis) AC and 51% incident AC were compared with unexposed controls (n = 91). The outcome was 28-days all-cause mortality after COVID-19 infection. The mortality odds ratios (OR) were assessed using logistic regression, adjusted for age, sex, multimorbidity, and mobility, also stratified by incident or prevalent AC-type, age group, and sex. Results: Of the 182 individuals diagnosed with COVID-19 (median age 88 years, 68% women), 39% died within 28 days after diagnosis. Use of either incident or prevalent AC was associated with a reduced, adjusted 28-day mortality (OR[95% CI]: 0.31[0.16-0.62]). In stratified analyses, the association was significant in both age groups: 70-89 (OR: 0.37 [0.15-0.89]) and 90-99 years of age (OR: 0.22 [0.07-0.65]. In sex-stratified analysis, the AC-lowering effect was significant in women only (OR: 0.28[0.11-0.67]). In the analyses stratified by AC type, the mortality-lowering effect was observed for both prevalent AC (OR: 0.35[0.12-0.99]) and incident AC (OR: 0.29[0.11-0.76]). Conclusions: Both prevalent and incident use of ACs in prophylactic dosing was associated with reduced 28-day mortality among older individuals with COVID-19 in a NH setting. The effect was seen across age-strata and in women. The findings present new insight in best practice for individuals diagnosed with COVID-19 in the NH setting.

Temporal dynamics of epigenetic aging and frailty from midlife to old age.

BACKGROUND: DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood. METHODS: This analysis included 1,309 repeated measurements in 524 individuals aged 50 to 90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including four principal component (PC)-based clocks trained on chronological age (PCHorvathAge, PCHannumAge) and aging-related physiological conditions (PCPhenoAge, PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations. RESULTS: The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa. CONCLUSION: Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level.

Recent developments in frailty identification, management, risk factors and prevention: A narrative review of leading journals in geriatrics and gerontology.

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles of geriatrics and gerontology (from Clarivate Journal Citation Reports) for articles published between 01 January 2018 and 20 December 2022. Several recent developments were identified, including new biomarkers and biomarker panels for frailty screening and diagnosis, using artificial intelligence to identify frailty, and investigating the altered response to medications by older adults with frailty. Other areas with novel developments included exercise (including technology-based exercise), multidimensional interventions, person-centred and integrated care, assistive technologies, analysis of frailty transitions, risk-factors, clinical guidelines, COVID-19, and potential future treatments. This review identified a strong need for the implementation and evaluation of cost-effective, community-based interventions to manage and prevent frailty. Our findings highlight the need to better identify and support older adults with frailty and involve those with frailty in shared decision-making regarding their care.

Is Frailty Different in Younger Adults Compared to Old? Prevalence, Characteristics, and Risk Factors of Early-Life and Late-Life Frailty in Samples from Sweden and UK.

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.

Rare functional variants in the CRP and G6PC genes modify the relationship between obesity and serum C-reactive protein in white British population.

BACKGROUND: C-reactive protein (CRP) is a sensitive biomarker of inflammation with moderate heritability. The role of rare functional genetic variants in relation to serum CRP is understudied. We aimed to examine gene mutation burden of protein-altering (PA) and loss-of-function (LOF) variants in association with serum CRP, and to further explore the clinical relevance. METHODS: We included 161,430 unrelated participants of European ancestry from the UK Biobank. Of the rare (minor allele frequency <0.1%) and functional variants, 1,776,249 PA and 266,226 LOF variants were identified. Gene-based burden tests, linear regressions, and logistic regressions were performed to identify the candidate mutations at the gene and variant levels, to estimate the potential interaction effect between the identified PA mutation and obesity, and to evaluate the relative risk of 16 CRP-associated diseases. RESULTS: At the gene level, PA mutation burdens of the CRP (ß = -0.685, p = 2.87e-28) and G6PC genes (ß = 0.203, p = 1.50e-06) were associated with reduced and increased serum CRP concentration, respectively. At the variant level, seven PA alleles in the CRP gene decreased serum CRP, of which the per-allele effects were approximately three to seven times greater than that of a common variant in the same locus. The effects of obesity and central obesity on serum CRP concentration were smaller among the PA mutation carriers in the CRP (pinteraction = 0.008) and G6PC gene (pinteraction = 0.034) compared to the corresponding non-carriers. CONCLUSION: PA mutation burdens in the CRP and G6PC genes are strongly associated with decreased serum CRP concentrations. As serum CRP and obesity are important predictors of cardiovascular risks in clinics, our observations suggest taking rare genetic factors into consideration might improve the delivery of precision medicine.

Unraveling the metabolic underpinnings of frailty using multicohort observational and Mendelian randomization analyses.

Identifying metabolic biomarkers of frailty, an age-related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance-based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two-sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (ß per SD increase = 0.37%, 95% confidence interval: 0.12-0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development.

Genetically and environmentally predicted obesity in relation to cardiovascular disease: a nationwide cohort study.

Background: Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity. We examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). Methods: We used cohort data from Swedish twins born before 1959 who had BMI measured between the ages of 40-64 years (midlife) or at the age of 65 years or later (late-life), or both, and prospective CVD information from nationwide register linkage through 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI. Individuals missing BMI or covariate data, or diagnosed with CVD at first BMI measure, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazard models to examine the association between BMI category and incident CVD, stratified by the PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI. Findings: Between 1984 and 2010, the 17,988 participants were enrolled in sub-studies of the Swedish Twin Registry. Midlife obesity was associated with a higher risk of CVD across all PGSBMI categories, but the association was stronger with genetically predicted lower BMI (hazard ratio from 1.55 to 2.08 for those with high and low PGSBMI, respectively). Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the PGSBMI. Results were similar when obesity was measured in late-life, but suffered from low power. Interpretation: Obesity was associated with CVD regardless of PGSBMI category, but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite genetically predicted low BMI). However, additional genetic factors, not captured by the PGSBMI, still influence the associations. Funding: The Strategic Research Program in Epidemiology at Karolinska Institutet; Loo and Hans Osterman's Foundation; Foundation for Geriatric Diseases at Karolinska Institutet; the Swedish Research Council for Health, Working Life and Welfare; the Swedish Research Council; and the National Institutes of Health.

Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging.

Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional generalized estimating equations were applied conditioning on individuals to estimate the drug effect on BA biomarker level within the same person when using or not using the drug. Chronological age, body mass index, smoking status, number of multiple medication uses, blood pressure, blood glucose level, and apoB/apoA ratio were adjusted for as covariates in the model. Overall, using antihypertensive drugs was associated with a decrease in one DNA-methylation age (PCGrimAge: beta = - 0.39, 95%CI = - 0.67 to - 0.12). When looking into drug subcategories, calcium channel blockers (CCBs) were associated with a decrease in several DNA-methylation ages (PCHorvathAge beta = - 1.28, 95%CI = - 2.34 to - 0.21; PCSkin&bloodAge beta = - 1.34, 95%CI = - 2.61 to - 0.07; PCPhenoAge beta = - 1.74, 95%CI = - 2.58 to - 0.89; PCGrimAge beta = - 0.57, 95%CI = - 0.96 to - 0.17) and in functional biological ages (functional age index beta = - 2.18, 95%CI = - 3.65 to - 0.71; frailty index beta = - 1.31, 95%CI = - 2.43 to - 0.18). However, the results within other drug subcategories were inconsistent. Calcium channel blockers may decrease biological aging captured by the BA biomarkers measured at epigenetic and functional level. Future studies are warranted to confirm these effects and understand the underlying biological mechanisms.

Clinical biomarker-based biological aging and risk of cancer in the UK Biobank.

BACKGROUND: Despite a clear link between aging and cancer, there has been inconclusive evidence on how biological age (BA) may be associated with cancer incidence. METHODS: We studied 308,156 UK Biobank participants with no history of cancer at enrolment. Using 18 age-associated clinical biomarkers, we computed three BA measures (Klemera-Doubal method [KDM], PhenoAge, homeostatic dysregulation [HD]) and assessed their associations with incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, and melanoma) using Cox proportional-hazards models. RESULTS: A total of 35,426 incident cancers were documented during a median follow-up of 10.9 years. Adjusting for common cancer risk factors, 1-standard deviation (SD) increment in the age-adjusted KDM (hazard ratio = 1.04, 95% confidence interval = 1.03-1.05), age-adjusted PhenoAge (1.09, 1.07-1.10), and HD (1.02, 1.01-1.03) was significantly associated with a higher risk of any cancer. All BA measures were also associated with increased risks of lung and colorectal cancers, but only PhenoAge was associated with breast cancer risk. Furthermore, we observed an inverse association between BA measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the BA algorithms. CONCLUSIONS: Advanced BA quantified by clinical biomarkers is associated with increased risks of any cancer, lung cancer, and colorectal cancer.

Can frailty scores predict the incidence of cancer? Results from two large population-based studies.

While chronological age is the single biggest risk factor for cancer, it is less clear whether frailty, an age-related state of physiological decline, may also predict cancer incidence. We assessed the associations of frailty index (FI) and frailty phenotype (FP) scores with the incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, melanoma) in 453,144 UK Biobank (UKB) and 36,888 Screening Across the Lifespan Twin study (SALT) participants, who aged 38-73 years and had no cancer diagnosis at baseline. During a median follow-up of 10.9 and 10.7 years, 53,049 (11.7%) and 4,362 (11.8%) incident cancers were documented in UKB and SALT, respectively. Using multivariable-adjusted Cox models, we found a higher risk of any cancer in frail vs. non-frail UKB participants, when defined by both FI (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.17-1.28) and FP (HR = 1.16; 95% CI = 1.11-1.21). The FI in SALT similarly predicted risk of any cancer (HR = 1.31; 95% CI = 1.15-1.49). Moreover, frailty was predictive of lung cancer in UKB, although this association was not observed in SALT. Adding frailty scores to models including age, sex, and traditional cancer risk factors resulted in little improvement in C-statistics for most cancers. In a within-twin-pair analysis in SALT, the association between FI and any cancer was attenuated within monozygotic but not dizygotic twins, indicating that it may partly be explained by genetic factors. Our findings suggest that frailty scores are associated with the incidence of any cancer and lung cancer, although their clinical utility for predicting cancers may be limited.

Health progression for Covid-19 survivors hospitalized in geriatric clinics in Sweden.

OBJECTIVE: To analyse if the health progression of geriatric Covid-19 survivors three months after an acute Covid-19 infection was worse than in other geriatric patients. Specifically, we wanted to see if we could see distinct health profiles in the flow of re-admitted Covid-19 patients compared to re-admitted non-Covid-19 controls. DESIGN: Matched cohort study. SETTING AND PARTICIPANTS: Electronic medical records of geriatric patients hospitalised in geriatric clinics in Stockholm, Sweden, between March 2020 and January 2022. Patients readmitted three months after initial admission were selected for the analysis and Covid-19 survivors (n = 895) were compared to age-sex-Charlson comorbidity index (CCI)-matched non-Covid-19 controls (n = 2685). METHODS: We assessed using binary logistic and Cox regression if a previous Covid-19 infection could be a risk factor for worse health progression indicated by the CCI, hospital frailty risk score (HFRS), mortality and specific comorbidities. RESULTS: The patients were mostly older than 75 years and, already at baseline, had typically multiple comorbidities. The Covid-19 patients with readmission had mostly had their acute-phase infection in the 1st or 2nd pandemic waves before the vaccinations. The Covid-19 patients did not have worse health after three months compared to the matched controls according to the CCI (odds ratio, OR[95% confidence interval, CI] = 1.12[0.94-1.34]), HFRS (OR[95%CI] = 1.05[0.87-1.26]), 6-months (hazard ratio, HR[95%CI] = 1.04[0.70-1.52]) and 1-year-mortality risk (HR[95%CI] = 0.89[0.71-1.10]), adjusted for age, sex and health at baseline (the CCI and HFRS). CONCLUSIONS AND IMPLICATIONS: The overall health progression of re-hospitalized geriatric Covid-19 survivors did not differ dramatically from other re-hospitalized geriatric patients with similar age, sex and health at baseline. Our results emphasize that Covid-19 was especially detrimental for geriatric patients in the acute-phase, but not in the later phase. Further studies including post-vaccination samples are needed.

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.