Frailty Predicts New and Persistent Depressive Symptoms Among Community-Dwelling Older Adults: Findings From Singapore Longitudinal Aging Study

ObjectiveThis study aimed to examine the cross-sectional and longitudinal relationships between physical frailty at baseline and depressive symptoms at baseline and at follow-up.DesignFour-year prospective study.SettingCommunities in the South East Region of Singapore.ParticipantsWe analyzed data of 1827 older Chinese adults aged 55 and above in the Singapore Longitudinal Aging Study-I.MeasurementsThe frailty phenotype (based on Fried criteria) was determined at baseline, depressive symptoms (Geriatric Depression Scale ≥5) at baseline and follow-ups at 2 and 4 years.ResultsThe mean age of the population was 65.9 (standard deviation 7.26). At baseline, 11.4% (n = 209) had depressive symptoms, 32.4% (n = 591) were prefrail and 2.5% (n = 46) were frail. In cross-sectional analysis of baseline data, the adjusted odds ratios (OR)s and 95% confidence intervals controlling for demographic, comorbidities, and other confounders were 1.69 (1.23–2.33) for prefrailty and 2.36 (1.08–5.15) for frailty, (P for linear trend <.001). In longitudinal data analyses, prospective associations among all participants were: prefrail: OR = 1.86 (1.08–3.20); frail: OR = 3.09 (1.12–8.50); (P for linear trend = .009). Among participants free of depressive symptoms at baseline, similar prospective associations were found: prefrail OR = 2.26 (1.12–4.57); frail: OR = 3.75 (1.07–13.16); (P for linear trend = .009).ConclusionThese data support a significant role of frailty as a predictor of depression in a relatively younger old Chinese population. Further observational and interventional studies should explore short-term dynamic and bidirectional associations and the effects of frailty reversal on depression risk.     

The Frailty Syndrome: A Comprehensive Review

The frailty syndrome is defined as unintentional weight and muscle loss, exhaustion, and declines in grip strength, gait speed, and activity. Evidence with respect to the clinical definition, epidemiology, mechanisms, interactions, assessment, prevention, and treatment of frailty in the older adult is reviewed.     

Malnutrition According to GLIM Criteria and Adverse Outcomes in Community-Dwelling Chinese Older Adults: A Prospective Analysis

ObjectivesThe Global Leadership Initiative on Malnutrition (GLIM) has proposed a consensus scheme for classifying malnutrition. This study examined the prevalence of malnutrition according to GLIM criteria and evaluated if these criteria were associated with adverse outcomes in community-dwelling older adults.DesignThis was a prospective cohort study.Setting and ParticipantsCommunity-dwelling Chinese men and women aged ≥65 years in Hong Kong.MethodsA health check including questionnaire interviews and physical measurements was conducted at baseline and 14-year follow-up. Participants were classified as malnourished at baseline according to the GLIM criteria based on 2 phenotypic components (low body mass index and reduced muscle mass) and 1 etiologic component (inflammation). Adverse outcomes including sarcopenia, frailty, falls, mobility limitation, hospitalization, and mortality were assessed at 14-year follow-up. Adjusted multiple logistic regression and Cox proportional hazards model were performed to examine the associations between malnutrition and adverse outcomes and presented as odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI).ResultsData of 3702 participants [median age: 72 years (IQR 68–76)] were available at baseline. Malnutrition was present in 397 participants (10.7%). Malnutrition was significantly associated with higher risk of sarcopenia (n = 898, OR 2.25; 95% CI 1.04–4.86), frailty (Fried (n = 971, OR 2.83; 95% CI 1.47–5.43), FRAIL scale (n = 985, OR 2.30; 95% CI 1.06–4.98)) and all-cause mortality (n = 3702, HR: 1.62; 95% CI 1.39–1.89). There was no significant association between malnutrition and falls (n = 987, OR 1.09; 95% CI 0.52–2.31), mobility limitation (n = 989, OR 0.98; 95% CI 0.36–2.67), and hospitalization (n = 989, OR 1.37; 95% CI 0.67–2.77).Conclusions and ImplicationsAmong community-dwelling Chinese older adults, malnutrition according to selected GLIM criteria was a predictor of sarcopenia, frailty, and mortality at 14-year follow-up; whereas no association was found for falls, mobility limitation, and hospitalization. Clinicians may consider applying the GLIM criteria to identify malnourished community-dwelling older adults.     

Association between Dysphagia and Frailty in Older Adults: A Systematic Review and Meta-Analysis

Background: Increasing bodies of epidemiological evidence indicate potential associations between dysphagia and the risk of frailty in older adults. We hypothesized that older adults with symptoms of dysphagia might have a higher prevalence of frailty or prefrailty than those without dysphagia. Methods: We systematically searched the PubMed, Embase, and Cochrane Library databases for relevant studies published through 20 April 2022. Cross-sectional and longitudinal studies that examined the associations between dysphagia and the existence of frailty or prefrailty in community-dwelling, facility-dwelling, or hospitalized adults aged 50 years or older were synthesized. The Newcastle–Ottawa Scale was used to evaluate study quality. Results: The meta-analysis comprised 12 cohorts, including 5,503,543 non-frailty participants and 735,303 cases of frailty or prefrailty. Random-effect meta-analysis demonstrated a significant association between dysphagia and the risk of frailty and prefrailty (OR, 3.24; 95% CI, 2.51–4.20). In addition, we observed consistent results across the subgroups and heterogeneity assessments. Conclusions: We propose including dysphagia assessment as a critical factor in the cumulative deficit model for identifying frailty in older adults. Understanding dysphagia and the potential role of nutritional supplements in older adults may lead to improved strategies for preventing, delaying, or mitigating frailty.     

Long Sleep Duration Is Associated With Higher Mortality in Older People Independent of Frailty: A 5-Year Cohort Study

ObjectivesAlthough general adult population studies show a U-shaped association between sleep duration and mortality, prolonged rather than short sleep duration was more consistently associated with higher mortality in older populations. Failing health or frailty is a possible mechanism. Thus, we examined the relationship among sleep duration, frailty status, and mortality in an elderly cohort.MethodsA total of 3427 community-living adults 65 years or older were examined for general health, mood, subjective sleep measures (insomnia, napping, sleep apnea, nighttime sleep duration, sleep medications), frailty, and 5-year mortality.ResultsAfter 5 years, 12.9% of men and 4.5% of women had died. Mean nighttime sleep duration was 7.3 hours. Proportion of participants who slept 10 or more hours increased with increasing frailty. Age-adjusted hazard ratio (HR) for 5-year mortality of long nighttime sleep (≥10 hours) was 2.10 (95% confidence interval [CI] 1.33–3.33) in men, and 2.70 (95% CI 0.98–7.46) in women. The HR in men was attenuated (HR 1.75; 95% CI 1.09–2.81) after adjustment for frailty and other covariates, whereas that of women strengthened (HR 2.88; 95% CI 1.01–8.18). Mortality increased sharply with nighttime sleep of 10 hours or more. Nighttime sleep of 10 or more hours (HR 1.75, men; HR 2.88, women) and frailty (HR 2.43, men; HR 2.08, P = .08 in women) were independently associated with 5-year mortality after full adjustment for covariates.ConclusionFrailty and long nighttime sleep duration of 10 or more hours were independently associated with 5-year mortality in older adults.     

Dietary Protein Intake and Transition between Frailty States in Octogenarians Living in New Zealand

Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship between dietary protein intake and the transition between frailty states and mortality in advanced age. We used data from a longitudinal cohort study of Māori (80–90 years) and non-Māori (85 years). Dietary assessments (24-h multiple pass dietary recalls) were completed at the second year of follow-up (wave 2 and forms the baseline in this study). Frailty was defined using the Fried Frailty criteria. Multi-state modelling examined the association of protein intake and transitions between frailty states and death over four years. Over three quarters of participants were pre-frail or frail at baseline (62% and 16%, respectively). Those who were frail had a higher co-morbidity (p < 0.05), where frailty state changed, 44% showed a worsening of frailty status (robust → pre-frail or pre-frail → frail). Those with higher protein intake (g/kg body weight/day) were less likely to transition from robust to pre-frail [Hazard Ratio (95% Confidence Interval): 0.28 (0.08–0.91)] but also from pre-frail to robust [0.24 (0.06–0.93)]. Increased protein intake was associated with lower risk of transitioning from pre-frailty to death [0.19 (0.04–0.80)], and this association was moderated by energy intake [0.22 (0.03–1.71)]. Higher protein intake in this sample of octogenarians was associated with both better and worse outcomes.     

Quality Specific Associations of Carbohydrate Consumption and Frailty Index

Background: The quality of carbohydrate consumed may influence the risk of frailty. In this study, we tested the hypothesis that indices of carbohydrate intake are associated with trajectories of frailty in participants of the Baltimore Longitudinal Study of Aging (BLSA). Methods: Cross sectional and longitudinal analyses were conducted in 1024 BLSA participants to examine the association between usual intake of carbohydrate and frailty index. Seven measures of carbohydrate consumption were estimated using data derived from Food Frequency Questionnaires (FFQs) and examined in association with a 43-item Frailty Index (FI). Results: In cross-sectional analyses, there was a significant, positive association between higher tertiles of total carbohydrate, glycemic load, and non-whole grains and FI. Conversely, higher tertiles of fiber-to-carbohydrate ratio was associated with lower FI. These differences persisted over the follow-up period of up to 13.8 years. Women in the highest tertile of the fiber-to-carbohydrate ratio showed a less steep increase in FI over time. Conclusions: Carbohydrate intake was positively associated with increased frailty risk in the BLSA participants, whereas a higher fiber-to-carbohydrate ratio was related to reduced risk for frailty.     

Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing

ObjectivesTo examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults.DesignCross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011.Participants and settingAdults age ≥50 years (n = 4068) living in the community in Ireland.MeasurementsCirculating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors.ResultsAdjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction.Conclusions and implicationsWe have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.     

Combined Impact of Traditional and Nontraditional Healthy Behaviors on Frailty and Disability: A Prospective Cohort Study of Older Adults

ObjectivesTo assess the short- and long-term association of 6 healthy behaviors (not smoking, vigorous to moderate physical activity, healthy diet, adequate sleeping duration, not being sedentary, and daily social interaction) with incident frailty and disability.DesignProspective population-based study.Settings and ParticipantsIn 2001, 4008 community-dwelling individuals aged ≥60 years in Spain were recruited. Participants were followed up until 2003, when a short-term phone interview of the remaining 3235 individuals was performed. Then, the participants were followed up until 2009, when a long-term phone interview was conducted with 1309 participants.MeasuresAt baseline, a home interview and a physical examination were conducted to assess healthy behaviors. At baseline and at follow-ups, we ascertained frailty and 4 domains of disability: limitation in instrumental activities of daily living, restriction in daily activities, limitation in mobility, and self-care limitation.ResultsIn the short-term analyses, vigorous to moderate physical activity and not being sedentary were associated with a reduction in frailty, multivariable odds ratios (OR) (95% confidence interval) 0.55 (0.35-0.85) and 0.43 (0.26-0.72). Vigorous to moderate physical activity and adequate sleeping duration decreased instrumental activities of daily living limitation OR 0.63 (0.44–0.91) and 0.69 (0.53–0.89) as well as self-care limitation OR 0.62 (0.41–0.92) and 0.65 (0.45-0.94). Adequate sleep duration and not being sedentary decreased restriction in daily activities OR 0.67 (0.49–0.90) and 0.57 (0.36–0.91). Vigorous to moderate physical activity and healthy diet decreased limitation in mobility OR 0.58 (0.35–0.96) and 0.73 (0.54–0.97). Considering these 5 healthy behaviors, participants who scored 5 (vs ≤ 2) in the combined score had a lower risk of frailty and disability. In the long-term analyses, results showed the same direction as in short-term analyses.Conclusions and ImplicationsThe combination of healthy behaviors is associated with a substantial reduction in the risk of frailty and of most disability outcomes in older adults.     

Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition,Cachexia, Sarcopenia,and Frailty: A Scoping Review

Cancer-associated malnutrition, or cachexia, stemming from cancer or its treatments, is particularly prevalent in metastatic cancers, and is often interrelated with sarcopenia and frailty. Evidence suggests that dietary supplements play a role in managing these conditions. As metastatic cancer cells are associated with notable genomic and phenotypic alterations, response to dietary supplements may differ between metastatic and non-metastatic cancers. However, research in this area is lacking. This scoping review aims to identify the dietary supplements that have been studied in patients with metastatic cancers and malnutrition-related conditions, along with their proposed effects, mechanisms, outcome measures, and tools used. A systematic search was conducted across databases, including MEDLINE, EMBASE, CINAHL, and clinical trial registries. Of the initial 6535 records screened, a total of 48 studies were included, covering a range of dietary supplements—vitamins, minerals, antioxidants, proteins, amino acids, fatty acids, fiber, and others. While the types of dietary supplements included varied across cancer types, omega-3 and carnitine were investigated most often. Proposed relevant attributes of dietary supplements included their antioxidant, anti-inflammatory, anti-cancer, and immunomodulatory properties. Overall, there was a paucity of interventional studies, and more randomized controlled trials are warranted.     

Effects of Milk Protein in Resistance Training-Induced Lean Mass Gains for Older Adults Aged ≥ 60 y: A Systematic Review and Meta-Analysis

This review evaluated the effects of milk-based protein supplementation on resistance training (RT)-induced gains in lean body mass or fat free mass (LBM/FFM) and muscle strength for older adults. A systematic search of PubMed, Scopus and EBSCOhost/SPORTDiscus was conducted. Eligibility criteria: Randomized controlled trials comparing all types of milk-based protein supplements with control supplements for the training older adults at mean age ≥ 60 y. Twenty studies were included in the qualitative synthesis, whilst seventeen studies were included in the quantitative synthesis. A dose of 10–15 g of milk protein supplementation was sufficient to augment RT-induced LBM/FFM. Intriguingly, four out of five studies show negative effect of whey protein supplementation at the same dose range (or even higher) compared with control supplementation (−0.49 kg, 95% CI: −0.69, −0.29, I² = 14%, Z = 4.82, p < 0.001). For milk-based protein supplementation, RT-induced improvements in muscle strength were observed only when the protein doses ≥22 g (+0.66 kg, 95% CI: 0.07, 1.25, I² = 0%, Z = 2.18, p = 0.03). Conclusion: Milk protein is superior to whey protein in enhancing RT-induced LBM/FFM gains for older adults. Optimal daily protein intake can dilute the protein supplementation effect.     

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.

Fatty Acids and Frailty: A Mendelian Randomization Study

Background: Observational studies have suggested that fatty acids such as higher levels of n-3 polyunsaturated fatty acids (PUFAs) may prevent frailty. By using Mendelian randomization analysis, we examined the relationship between fatty acids and frailty. Methods: We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of saturated fatty acids (palmitic acid, stearic acid), mono-unsaturated fatty acids (MUFAs) (palmitoleic acid, oleic acid), n-6 PUFAs (linoleic acid, arachidonic acid), and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), and the corresponding data for frailty index (FI) in 356,432 individuals in the UK Biobank. Results: Although there were no robust associations on the MUFAs or the PUFAs, genetically predicted higher plasma stearic acid level (one of saturated fatty acids) was statistically significantly associated with higher FI (β = 0.178; 95% confidence interval = −0.050 to 0.307; p = 0.007). Such a relationship was also observed in a multivariate MR (β = 0.361; 95% confidence interval = 0.155 to 0.567; p = 0.001). Genetically predicted higher palmitic acid was also significantly associated with higher FI (β = 0.288; 95% confidence interval = 0.128 to 0.447; p < 0.001) in the multivariate MR analysis. Conclusions: The present MR study implies that saturated fatty acids, especially stearic acid, is a risk factor of frailty.     

Association of Depressive Mood and Frailty With Mortality and Health Care Utilization: Korean National Cohort Study

ObjectivesTo investigate the association of depressive mood and frailty with mortality and health care utilization (HCU) and identify the coexisting effect of depressive mood and frailty in older adults.DesignA retrospective study using nationwide longitudinal cohort data.Setting and ParticipantsA total of 27,818 older adults age 66 years from the National Screening Program for Transitional Ages between 2007 and 2008, part of the National Health Insurance Service–Senior cohort.MethodsDepressive mood and frailty were measured by the Geriatric Depression Scale and Timed Up and Go test, respectively. Outcomes were mortality and HCU, including long-term care services (LTCS), hospital admissions, and total length of stay (LOS) from the index date to December 31, 2015. Cox proportional hazards regression and zero-inflated negative binomial regression were performed to identify differences in outcomes by depressive mood and frailty.ResultsParticipants with depressive mood and frailty represented 50.9% and 2.4%, respectively. The prevalence of mortality and LTCS use in the overall participants was 7.1% and 3.0%, respectively. More than 3 hospital admissions (36.7%) and total LOS above 15 days (53.2%) were the most common. Depressive mood was associated with LTCS use [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.05–1.42] and hospital admissions [incidence rate ratio (IRR) 1.05, 95% CI 1.02–1.08]. Frailty had associations with mortality risk (HR 1.96, 95% CI 1.44–2.68), LTCS use (HR 4.86, 95% CI 3.45–6.84), and LOS (IRR 1.30, 95% CI 1.06–1.60). The coexistence of depressive mood and frailty was associated with increased LOS (IRR 1.55, 95% CI 1.16–2.07).Conclusions and ImplicationsOur findings highlight the need to focus on depressive mood and frailty to reduce mortality and HCU. Identifying combined problems in older adults may contribute to healthy aging by reducing adverse health outcomes and the burden of health care costs.     

Mediation of Healthy Behaviour on the Association of Frailty with Respiratory Diseases Mortality among 0.4 Million Participants: A Prospective Cohort Study from UK Biobank

The mutual relationship between frailty and healthy behaviour and its effect on respiratory diseases mortality remains largely unknown; this study aims to supplement related analysis on it by using a large sample cohort study. We included 411,987 participants from the UK Biobank study (2006–2021), and measured participants’ frailty phenotype and healthy behaviour index by using questionnaires and physical measurement. Mortality from respiratory diseases were obtained through linkage to registries. We used the cox proportional hazards model to explore the association of frailty with respiratory diseases mortality, and calculated the mediation proportion of the healthy behaviour. During a median follow-up of 12.48 years, and after adjustment for other covariates and healthy behaviour index, when compared with non-frail participants, being frail was associated with 2.68 times, 3.27 times, and 3.31 times higher risk of total respiratory diseases mortality, influenza and pneumonia mortality and chronic lower respiratory diseases mortality, respectively. The attenuated proportions mediated by healthy behaviour were 5.1% (95% CI: 4.4%, 5.9%), 3.0% (95% CI: 2.1%, 4.2%) and 6.0% (95% CI: 4.9%, 7.4%), respectively. Compared with non-frail individuals with four or five healthy behaviours, frail individuals with no or one healthy behaviour had higher risks of total respiratory diseases mortality (aHR = 4.59; 95% CI: 3.27, 6.45), influenza and pneumonia mortality (aHR = 4.55; 95% CI: 2.30, 9.03), as well as chronic lower respiratory diseases mortality (aHR = 12.70; 95% CI: 5.76, 27.96). Adherence to a healthy lifestyle therefore represents a potentially modifiable target for improving the harmful impact of frailty on reduced life expectancy as a result of respiratory diseases.     

Whey Protein Supplementation Improves Rehabilitation Outcomes in Hospitalized Geriatric Patients: A Double Blinded,Randomized Controlled Trial

Whey protein supplementation (WPS) has been shown to improve functional outcomes in populations that are able to participate in high-intensity resistance training. The purpose of the study was to evaluate the efficacy of WPS on rehabilitation outcomes in a frail, hospitalized elderly population. Men and women (n?=?47) were randomly assigned to either a control group or WPS group for the length of their hospital stay. Several functional and serum measures were determined pre- and post-intervention. WPS significantly increased average daily protein intake and was well tolerated. The WPS group exhibited significant improvements in grip strength and knee extensor force over the control group, and a significant positive correlation was found between change in prealbumin and percent-increase knee extensor force. These findings support the use of WPS to improve protein nutritional status and rehabilitation outcomes in a clinical setting involving a frail, elderly population.     

The Relationship of Oral Health with Progression of Physical Frailty among Older Adults: A Longitudinal Study Composed of Two Cohorts of Older Adults from the United Kingdom and United States

ObjectiveTo investigate the prospective associations between oral health and progression of physical frailty in older adults.DesignProspective analysis.Setting and ParticipantsData are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years.MethodsOral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors.ResultsAfter full adjustment, progression to frailty was associated with dentition [per each additional tooth, odds ratio (OR) 0.97; 95% CI: 0.95–1.00], <21 teeth with (OR 1.74; 95% CI: 1.02–2.96) or without denture use (OR 2.45; 95% CI 1.15–5.21), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06–3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 2.62; 95% CI 1.05–6.55), self-reported difficulty eating (OR 2.12; 95% CI 1.28–3.50) and ≥2 cumulative oral health problems (OR 2.29; 95% CI 1.17–4.50). Progression to severe frailty was associated with edentulism (OR 4.44; 95% CI 1.39–14.15) and <21 teeth without dentures after full adjustment.Conclusions and ImplicationsThese findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults.     

Frailty Defined by FRAIL Scale as a Predictor of Mortality: A Systematic Review and Meta-analysis

Objectives

To conduct a systematic review of the literature on prospective cohort studies examining mortality risk according to frailty defined by FRAIL scale, and to perform a meta-analysis to synthesize the pooled risk estimates.