Frailty Trajectories Research Articles

The frailty risk trajectory associated with kidney and cardiovascular morbidities among patients with incident diabetes: A population-based study

Background and aimsFrailty denotes the increased vulnerability to stressors/insults associated with aging or diseases, and has high incidence in patients with diabetes mellitus (DM). We hypothesized that chronic kidney disease (CKD) and non-kidney morbidities in patients with newly diagnosed DM might modulate their risk of developing incident frailty. MethodsFrom the Longitudinal Cohort of Diabetes Patients, we identified 322,109 patients with newly diagnosed DM, and classified them into those without CKD, with CKD before and after DM. We used Kaplan-Meier analyses and Cox proportional hazard regression to analyze associations between CKD or non-kidney morbidities and the risk of incident frailty. We further analyzed the year-to-year trend of frailty risk brought by CKD or non-kidney morbidities. ResultsPatients with DM but without CKD (n = 249,752; 77.5%), with CKD prior to (n = 23,829; 7.4%), and after DM (n = 48,528; 15.1%) were enrolled. Those with CKD, regardless of onset timing, had a significantly higher risk of developing frailty than those without (for onset prior to DM, hazard ratio (HR) 1.235, 95% confidence interval (CI) 1.11–1.38; for onset after DM, HR 1.386, 95% CI 1.21–1.59). The risk was more prominent early after the diagnosis of DM was made. Patients with chronic obstructive pulmonary disease, liver, and cardiovascular morbidities all had a significantly higher risk of frailty than those without, with cerebrovascular accident carrying the most prominent risk elevation (HR 4.059, 95% CI 3.73–4.42). ConclusionsCKD regardless of onset timing relative to DM predicted a higher risk of incident frailty, while non-kidney morbidities including cardiovascular morbidities, similarly increased frailty risk among incident diabetic patients.

Natural History Trajectories of Frailty in Community-Dwelling Older Japanese Adults.

BackgroundThe gap between the average life expectancy and healthy life expectancy remains wide. Understanding the natural history of frailty development is necessary to prevent and treat frailty to overcome this gap. This study elucidated the trajectories of 5 frailty assessment components using group-based multitrajectory modeling.MethodsOverall, 845 community-dwelling older adults (aged 65–91 years; 433 males and 412 females) who underwent longitudinal frailty assessments at least 3 times were included in the analysis. The mean follow-up period (±SD, range) was 7.1 (±2.3, 3.8–11.3) years. In each wave, the physical frailty was assessed for the following 5 partially modified components of the Cardiovascular Health Study criteria: shrinking, weakness, exhaustion, slowness, and low activity. Using group-based multitrajectory modeling, we identified subgroups that followed distinctive trajectories regarding the 5 frailty components.ResultsFive frailty trajectory groups were identified: weakness-focused frail progression group (Group 1 [G1]; 10.9%), robust maintenance group (Group 2 [G2]; 43.7%), exhaustion-focused prefrail group (Group 3 [G3]; 24.3%), frail progression group (Group 4 [G4]; 6.7%), and low activity–focused prefrail group (Group 5 [G5]; 14.4%). The Cox proportional hazards model analysis showed that G1, G4, and G5 had significantly higher mortality risks after adjusting for sex and age (G2 was the reference group).ConclusionBased on the natural history of frailty, the 5 distinctive trajectory groups showed that some individuals remained robust, while others remained predominantly prefrail or progressed primarily owing to physical mobility decline. Therefore, identifying individuals belonging to these progressive frailty groups and providing interventions according to the characteristics of each group may be beneficial.

Mediating Effect of Physical Activity in the Association between Low 25-Hydroxyvitamin D and Frailty Trajectories: The English Longitudinal Study of Ageing.

BACKGROUND: Frailty is associated with adverse health outcomes, and vitamin D (VD) deficiency may be a risk factor. We aimed to identify frailty trajectories and examine the mediating effect of physical activity (PA) on the association between VD deficiency and frailty trajectories. METHODS: We included 2997 participants aged 60 to 85 years from ELSA. VD was measured using serum 25-hydroxyvitamin D [25(OH)D] (sufficient: >50; insufficient: 30–50; deficient: <30 nmol/L). Frailty was assessed by a 60-item frailty index, and PA was measured on the basis of total energy expenditure. Frailty trajectories were identified using group-based trajectory modeling, and the mediation effect of PA was tested using causal mediation analysis. RESULTS: Three distinct frailty trajectories emerged: “Non-frail” (66.48%), “Pre-frail to frail” (25.67%) and “Frail to severely frail” (7.85%). VD deficiency was associated with the “Pre-frail to frail” (OR = 1.51, 95% CI: 1.14, 1.98) and “Frail to severely frail” trajectories (OR = 2.29, 95% CI: 1.45, 3.62). PA only mediated 48.4% (95% CI: 17.1%–270.8%) of the association between VD deficiency and the “Pre-frail to frail” trajectory. CONCLUSIONS: Vitamin D deficiency is associated with the onset and worsening of frailty in older adults, and reduced PA may mediate its impact on the transition from pre-frailty to frailty.

The Association between Trajectories of Loneliness and Physical Frailty in Chinese Older Adults: Does Age Matter?

Background: The present study aimed to examine age differences in the relationship between trajectories of loneliness and physical frailty among Chinese older adults. Methods: A total of 4618 participants aged ≥60 years old were taken from pooled data created from the 2011–2015 China Health and Retirement Longitudinal Study (CHARLS). Loneliness was assessed by a single question from the Centre for Epidemiological Studies scale, whereas physical frailty (PF) was examined by the physical frailty phenotype scale. We characterized trajectories of loneliness and PF using transition types and changes within the survey period. Results: Logistic regression models revealed that baseline loneliness was significantly related to remaining robust PF (OR = 0.55, 95% CI = 0.49–0.63, p < 0.001) and worsening in PF (OR = 1.17, 95% CI = 1.05–1.30, p < 0.01) at follow-up. Baseline PF status was also significantly related to the transitions in loneliness (worsen: OR = 1.41, 95% CI = 1.11–1.78, p < 0.01; improve: OR = 0.65, 95% CI = 0.47–0.91, p < 0.05). The cross-lagged panel model found that baseline PF or loneliness had a significant predictive effect on the changes in each other. The associations between trajectories of loneliness and PF were weakened with age and clustered in the under 75 age groups. Conclusions: Bidirectional associations may exist between trajectories of loneliness and PF among Chinese older adults. Interventions should mainly target the young-old to reduce the adverse reciprocal effects of loneliness and PF.

Trajectories of physical frailty and cognitive impairment in older adults in United States nursing homes

BackgroundU.S. nursing homes provide long-term care to over 1.2 million older adults, 60% of whom were physically frail and 68% had moderate or severe cognitive impairment. Limited research has examined the longitudinal experience of these two conditions in older nursing home residents.MethodsThis national longitudinal study included newly-admitted non-skilled nursing care older residents who had Minimum Data Set (MDS) 3.0 (2014–16) assessments at admission, 3 months, and 6 months (n = 266,001). Physical frailty was measured by FRAIL-NH and cognitive impairment by the Brief Interview for Mental Status. Separate sets of group-based trajectory models were fitted to identify the trajectories of physical frailty and trajectories of cognitive impairment, and to estimate the association between older residents’ characteristics at admission with each set of trajectories. A dual trajectory model was used to quantify the association between the physical frailty trajectories and cognitive impairment trajectories.ResultsOver the course of the first six months post-admission, five physical frailty trajectories [“Consistently Frail” (prevalence: 53.0%), “Consistently Pre-frail” (29.0%), “Worsening Frailty” (7.6%), “Improving Frailty” (5.5%), and “Consistently Robust” (4.8%)] and three cognitive impairment trajectories [“Consistently Severe Cognitive Impairment” (35.5%), “Consistently Moderate Cognitive Impairment” (31.8%), “Consistently Intact/Mild Cognitive Impairment” (32.7%)] were identified. One in five older residents simultaneously followed the trajectories of “Consistently Frail” and “Consistently Severe Cognitive Impairment”. Characteristics associated with higher odds of the “Improving Frailty”, “Worsening Frailty”, “Consistently Pre-frail” and “Consistently Frail” trajectories included greater at-admission cognitive impairment, age ≥ 85 years, admitted from acute hospitals, cardiovascular/metabolic diagnoses, neurological diagnoses, hip or other fractures, and presence of pain. Characteristics associated with higher odds of the “Consistently Moderate Cognitive Impairment” and “Consistently Severe Cognitive Impairment” included worse at-admission physical frailty, neurological diagnoses, hip fracture, and receipt of antipsychotics.ConclusionsFindings provided information regarding the trajectories of physical frailty, the trajectories of cognitive impairment, the association between the two sets of trajectories, and their association with residents’ characteristics in older adults’ first six months post-admission to U.S. nursing homes. Understanding the trajectory that the residents would most likely follow may provide information to develop a comprehensive care approach tailored to their specific healthcare goals.

Reward System Dysfunction and the Motoric-Cognitive Risk Syndrome in Older Persons.

During aging, many physiological systems spontaneously change independent of the presence of chronic diseases. The reward system is not an exception and its dysfunction generally includes a reduction in dopamine and glutamate activities and the loss of neurons of the ventral tegmental area (VTA). These impairments are even more pronounced in older persons who have neurodegenerative diseases and/or are affected by cognitive and motoric frailty. All these changes may result in the occurrence of cognitive and motoric frailty and accelerated progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. In particular, the loss of neurons in VTA may determine an acceleration of depressive symptoms and cognitive and motor frailty trajectory, producing an increased risk of disability and mortality. Thus, we hypothesize the existence of a loop between reward system dysfunction, depression, and neurodegenerative diseases in older persons. Longitudinal studies are needed to evaluate the determinant role of the reward system in the onset of motoric-cognitive risk syndrome.

Effects of social support on frailty trajectory classes among community-dwelling older adults: The mediating role of depressive symptoms and physical activity

ObjectivesTo investigate whether and how social support influenced frailty progression through depressive symptoms and physical activity. MethodsOf 1235 community-dwelling older adults enrolled at baseline, 778 (63.0%) undergoing at least one yearly follow-up were included in the final analysis. Data were collected on frailty, social support, depressive symptoms, physical activity and covariates. ResultsTwo frailty trajectory classes were identified and labeled as alleviated frailty and deteriorated frailty. Subjective support prevented the deterioration of frailty through decreased depressive symptoms, while objective support and support utilization prevented the deterioration of frailty through increased physical activity. ConclusionsThe pathways through which social support ameliorates frailty vary by support types. Subjective support interventions should be included in the multifactorial interdisciplinary management of frailty to address social and psychological vulnerabilities, along with objective support and support utilization interventions addressing physical inactivity.

Prognostic Signature of Chronic Kidney Disease in Advanced Age: Secondary Analysis from the InGAH Study with One-Year Follow-Up.

The negative impact of chronic kidney disease (CKD) on health status and quality of life in older patients has been well documented. However, data on frailty trajectories and long-term outcomes of older CKD patients undergoing structured Comprehensive Geriatric Assessment (CGA) with multidimensional frailty evaluation are sparse. Here, we analysed records from 375 CKD patients admitted to our university hospital (mean age 77.5 (SD 6.1) years, 36% female) who had undergone a CGA-based calculation of the frailty score with the multidimensional prognostic index (MPI) as well as follow-up evaluations at 3, 6 and 12 months after discharge. Based on the MPI score at admission, 21% of the patients were frail and 56% were prefrail. MPI values were significantly associated with KDIGO CKD stages (p = 0.003) and rehospitalisation after 6 months (p = 0.027) and mortality at 3, 6 and 12 months (p = 0.001), independent of chronological age. Kidney transplant recipients (KTR) showed a significantly lower frailty compared to patients with renal replacement therapy (RRT, p = 0.028). The association between frailty and mortality after 12 months appeared particularly strong for KTR (mean MPI 0.43 KTR vs. 0.52 RRT, p < 0.001) and for patients with hypoalbuminemia (p < 0.001). Interestingly, RRT was per se not significantly associated with mortality during follow up. However, compared to patients on RRT those with KTR had a significantly lower grade of care (p = 0.031) and lower rehospitalisation rates at 12 months (p = 0.010). The present analysis shows that the large majority of older CKD inpatients are prefrail or frail and that the risk for CKD-related adverse outcomes on the long term can be accurately stratified by CGA-based instruments. Further studies are needed to explore the prognostic and frailty-related signature of laboratory biomarkers in CKD.

Neighborhood resources associated with frailty trajectories over time among community-dwelling older adults in China.

Recent research has identified neighborhoods as an important contributor to later-life frailty. However, little is known about how neighborhood resources are associated with frailty trajectories over time, especially in developing countries. This study examines the impact of neighborhood physical and social resources on the trajectories of frailty over time among older people in China. Using the four waves of the China Health and Retirement Longitudinal Study (2011-2018), 5673 respondents aged 60 and above at baseline were included for analyses. Multilevel growth modeling was fitted to estimate the effects of neighborhood resources on frailty trajectories over a 7-year period, controlling for individual-level characteristics. Older Chinese people who lived in neighborhoods with better basic infrastructures and a greater number of voluntary organizations were less frail at baseline. Accessible exercise facilities were associated with a lower initial level of frailty only among rural older adults, while higher community-level socioeconomic status (SES) was associated with a lower initial level of frailty only among urban older adults. Over the 7-year follow-up period, better basic infrastructures and accessible exercise facilities were associated with a slower increase rate of frailty scores among rural residents. Neighborhood resources are important contributors to the level of frailty among older Chinese people. Our findings of significant urban-rural differences have important implications for designing and implementing infrastructure development and community building programs in rural and urban China.

Long-Term Trajectories of Frailty and Its Components After Kidney Transplantation.

Frailty is common and associated with poor outcomes among kidney transplant (KT) recipients. While frailty improves in the first 3 months post-KT with restored kidney function, longer-term trajectories are likely to plateau/decline due to aging and other stressors (eg, immunosuppression). We evaluated longer-term post-KT trajectories of the physical frailty phenotype (PFP) and its components in adult patients at 2 centers. PFP components were measured at admission, 1, 3, 6 months, 1 year, and annually thereafter post-KT. We used adjusted mixed-effects models to describe repeated measures of continuous components (weight, gait speed, grip strength, activity) and generalized estimating equations to quantify longitudinal, binomial response patterns (PFP; exhaustion). Among 1 336 recipients (mean age = 53) followed for a median of 1.9 years (interquartile range [IQR] = 0.1-3.2), likelihood of frailty declined in the first 2.5 years post-KT (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI]: 0.95, 0.98), but increased after 2.5 years post-KT (aOR = 1.03, 95% CI: 1.00, 1.05). In the first 2.5 years post-KT, recipients demonstrated increases in weight (0.4 lbs/month, 95% CI: 0.3, 0.5), grip strength (0.2 kg/month, 95% CI: 0.1, 0.2), and activity (23.9 kcal/month, 95% CI: 17.5, 30.2); gait speed remained stable (-0.01 s/month, 95% CI: 0.01, 0.003). Additionally, likelihood of becoming exhausted declined post-KT (OR = 0.99, 95% CI: 0.98, 1.00). After 2.5 years post-KT, recipients demonstrated decreased grip strength (-0.07 kg/month, 95% CI: -0.12, -0.01) and activity (-20 kcal/month, 95% CI: -32.3, -8.2); they had stable weight (-0.003 lbs/month, 95% CI: -0.17, 0.16), gait speed (-0.003 s/month, 95% CI: -0.02, 0.01), and likelihood of becoming exhausted (OR = 1.01, 95% CI: 0.99, 1.02). Despite frailty improvements in the first 2.5 years, recipients' frailty worsened after 2.5 years post-KT. Specifically, they experienced gains in strength, activity, and exhaustion in the first 2.5 years post-KT, but declined in strength and activity after 2.5 years post-KT while experiencing persistent slowness. Clinicians should consider monitoring recipients for worsening frailty after 2.5 years despite shorter-term improvements.

Frailty and functional dependence in older population: lessons from the FREEDOM Limousin \u2013 Nouvelle Aquitaine Cohort Study

BackgroundMonitoring frailty indicators in elderly people is recommended to identify those who could benefit from disability prevention programs. To contribute to the understanding of the development of frailty in the elderly, we have created the FREEDOM-LNA cohort constituting an observational study of ageing in general population. Here, we described the characteristics of a cohort of elderly subjects who are followed for determination of frailty and loss of independence trajectories.ResultsThe cohort was composed of 1085 subjects in advanced age (mean: 83.7 ± 6.0 years) and of women in majority (68.3%). Cardiovascular risk factors were present in 88.4% of subjects. Abnormal musculoskeletal signs were reported in 44.0% and neurologic signs in 31.9%. There were 44.8% of subjects at risk of malnutrition (MNA <24) and 73.3% (668/911) at risk of mobility-related disability (SPPB ≤9); 39% (384/973) of subjects had impaired cognitive function (MMSE< 24, adjusted on education) and 49.0% (397/810) had signs of depression (GDS >9); 31.8% (240/753) were frail and 58.3% were pre-frail. Most subjects had at least one disability in ADL (66.9%) and IADL (85.1%). The SMAF indicated a loss of independence in 59.6%. Overall, 59.9% of subjects could not stay at home without at least some help. Consequently, a medical consultation was proposed in 68.2 and 42.1% social supports.ConclusionsA large part of this cohort was frail or pre-frail and presented signs of loss of independence, which may be explained by multiple factors including impaired health status, poor physical performance, cognition, isolation, depression, or nutrition. This cohort will help to determine factors that adversely influence the trajectory of physical frailty over time.

Trajectories of Frailty With Aging: Coordinated Analysis of Five Longitudinal Studies.

Background and ObjectivesThere is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education.Research Design and MethodsWe derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term.ResultsModels describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves.Discussion and ImplicationsOur findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

Cardiac surgery improves the postoperative frailty score of frail patients.

Cardiac surgery in frail patients has been reported to be associated with increased mortality and morbidity but may improve functional status of frail patients. Few studies have investigated the impact of cardiac surgery on the trajectory of postoperative frailty. We hypothesized that cardiac surgery in frail patients would improve frailty postoperatively. This study included 71 patients over 65years old who were scheduled for cardiac surgery via sternotomy or thoracotomy. Frailty was prospectively evaluated using the Kihon Checklist (KCL) at 1 and 3months postoperatively. Patients were divided into three groups based on the preoperative KCL score: nonfrail, prefrail, and frail. The interaction between the degree of preoperative frailty and the trajectory of postoperative KCL scores was assessed. The KCL score changed significantly over time (P < 0.001), and the KCL score trajectory differed significantly according to the degree of preoperative frailty (P for interaction = 0.003). In the frail group, the KCL score was significantly lower 3months postoperatively than preoperatively (median 8, interquartile range [5, 9] versus median 9, interquartile range (9, 13), P = 0.029). The trajectory of postoperative KCL scores differed significantly depending on the degree of preoperative frailty. At 3months after cardiac surgery, the KCL score of frail patients was significantly improved, while that in nonfrail patients was significantly deteriorated.

The impact of frailty on health outcomes in older adults with lung cancer: A systematic review

Background: Frailty is prevalent in older adults with lung cancer, however the impact of frailty in this population is not well understood. The aim of this review was to evaluate the outcomes that are measured in frail older adults with lung cancer, and to determine the associations between frailty and these outcomes. Methods: A systematic online search of PubMed, EMBASE, and Cochrane databases was conducted to identify all English-language studies between January 2015 and May 2022 prospectively evaluating frailty and outcomes in older adults (median age > 65 years) with lung cancer. Studies were excluded if frailty was defined by a single domain assessment or not clearly defined. Quality was assessed using the Newcastle-Ottawa Scale. Results: Of 1891 studies screened, 16 met inclusion criteria. The median number of patients was 96 (range 26–494) and the mean age was 76.6 years. Eight different frailty assessments were used, and frailty definitions varied widely. The most frequently assessed outcomes were overall survival (n = 13,81%), treatment-related toxicity (n = 8,50%), hospitalisation (n = 5,31%), and treatment completion/discontinuation (n = 4,25%). Quality of life (n = 3,19%), function (n = 1,6%), frailty trajectory (n = 1,6%), and emergency visits (n = 1,6%) were infrequently assessed.Frailty had a strong and consistent association with mortality (Hazard Ratio range: 3.5–11.91). It was also associated with treatment-related toxicity and treatment selection. The remaining outcomes were not statistically significant. Conclusion: These data support frailty as an important predictor of mortality in older adults with lung cancer, however further research is warranted to determine the association between frailty and other meaningful endpoints for this vulnerable population.

Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.

BackgroundThe association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one‐off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels.MethodsParticipants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow‐up (median 5.04 years) were used to construct frailty trajectories according to group‐based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital.ResultsNine hundred and seventy‐five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non‐frailty (WNF), improving to non‐frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21–3.32]; RF = 1.92 [1.18–3.12]; IF = 2.67 [1.48–4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11–3.82); RF = 2.29 (1.30–4.03); IF = 3.55 (1.37–9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19–3.76); RF = 2.14 (1.26–3.64); IF = 2.21 (1.06–4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose–response relationship between baseline FTS5 score and adverse events.ConclusionsBelonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.

Trajectory and Correlation of Intrinsic Capacity and Frailty in a Beijing Elderly Community.

Objectives: The World Health Organization proposed intrinsic capacity (IC) model to guide the implementation of person-centered care plan aimed at preserving or reserving functional ability, especially in frail older adults. We aimed to show the trajectory of IC and the overlap between IC impairment and frailty and investigate the correlation between IC domains and frailty status transitions.Method: Longitudinal observational study covering 230 community-dwelling older adults (mean age 84.0 ± 4.5 years) at baseline, and transition information at 2-year follow-up (n = 196). IC was measured by five domains: locomotion, cognition, vitality, psychological, and sensory. Frailty was defined by FRAIL Scale. IC and frailty status transitions were assessed. Logistic regression, odds ratios (OR) and 95% confidence interval (CI) were used for the analysis.Results: The prevalence of frailty was 23.0% and increased up to 41.8% over two years. Regarding frailty transitions, 38.3% of older adults progressed to more frailty status, and 8.6% regressed to lesser frailty status. The prevalence of IC impairment was 67.9% and increased to 81.6% over two years. Regarding IC transitions, 49.2% of adults with no IC impairment at baseline kept stable, and 50.8% developed new IC impairment. Among individuals with IC impairment at baseline, 57.9% worsened, and 13.5% improved. Importantly, IC impairment at baseline existed in 42.4% robust adults, 83.3% pre-frail adults, and 93.3% frail adults. 47.1% individuals who kept non-frail status within two years experienced IC worsened transition. Univariable analysis illustrated that new impaired locomotion, vitality, cognition, and sensory domains increased the risk of non-frail progressed to frail status. After adjusting for covariables, new impaired locomotion (OR = 3.625, 95% CI: 1.348–9.747) and vitality domains (OR = 3.034, 95% CI: 1.229–7.487) were associated with a higher possibility of non-frail progressed to frail status.Conclusion: IC impairment and frailty overlap and co-exist in older adults. IC impairment, especially new impairment in locomotion and vitality are associated with the transitions from non-frail to frail status. It is important that geriatricians tightly monitor IC trajectory and find the new impaired domains to take early action to minimize the public health burden of frailty.

10-year frailty trajectory is associated with Alzheimer's dementia after considering neuropathological burden.

Main ProblemFrailty is an established risk factor for cognitive decline and Alzheimer's disease. Few studies have examined the longitudinal relationship between frailty and cognition.MethodsParticipants of Rush Memory and Aging project (n = 625, 67.5% female, 83.2 ± 5.9 years at baseline) underwent annual clinical evaluations (average follow‐up 5.6 ± 3.7 years) followed by neuropathologic assessment after death. A frailty index was calculated from 41 health variables at each evaluation. Clinical diagnosis of MCI and/or dementia was ascertained by clinical data review (blinded to neuropathological data) after death. Age, sex, education, and neuropathological burden (10‐item index) were evaluated as covariates. Frailty trajectories were calculated using a mixed effects model.ResultsAt baseline the mean frailty index = 0.24 ± 0.12 and increased at rate of 0.026 or ~1 deficit per year. At death, 27.7% of the sample had MCI, and 38.6% had dementia. Frailty trajectories were significantly steeper among those individuals who were ultimately diagnosed as clinically impaired prior to death, even after controlling for age, sex, education, and neuropathological index.ConclusionsFindings suggest a strong link between health status (frailty index) and dementia, even after considering neuropathology. Frailty trajectories were associated with risk for MCI and dementia, underscoring the importance of addressing frailty to manage dementia risk.

Frailty and dementia in long‐term care: An analysis of the InterRAI data over the past decade

Older adults in long-term care are typically frail with multiple health problems and functional impairments; many have dementias of Alzheimer's disease (AD) or other types. Frailty and dementia have a complex relationship; deterioration in one can make people more susceptible to the other. The association between frailty and dementia in long-term care is not well understood. We conducted this study to investigate 1) how frailty differed by AD and dementia diagnoses in long-term care residents, and 2) whether the relationship between frailty and dementia changes over time. Data were retrieved from the InterRAI Residential Care assessments conducted in Fraser Health, Canada. Participants aged 65 years and over at the time of admission to one of the 83 long-term care facilities between 2010 and 2019 (number of participants n=25,744; mean age=84.7±7.7 (85-111) years; 63.2% females) were included in the study. Diagnosis of AD (n=4,055) and other dementias (n=11,882) were recorded during the assessment. A frailty index (FI) was calculated for each participant using 36 variables from their first full MDS2.0 assessment. Deficits included diseases, symptoms, functions, nutrition and other health conditions. The FI was presented as the ratio of deficits present over the total number of deficits considered (i.e., 36 here; higher FI indicating more deficits). Group mean differences of the FI were examined using ANOVA. Relations of the FI with AD and dementia diagnoses were examined using multivariate regressions, adjusted for year of assessment and demographics. The FI of the individuals increased exponentially with age (r=0.127, p<0.001) and differed significantly among diagnoses (no dementia=0.369±0.137, AD=0.394±0.144, other dementias=0.422±0.144, F=370.15, p<0.001). The 99% limits of the FI ranged 0.686 - 0.736, depending on assessment year. Frailty increased dementia risks: a 1% increase of the FI was associated with 2.7% (95% confidence interval CI=2.4-2.9) higher risk for other dementias and 1.4% (1.1-1.6) for AD, independent of the effects of age, sex, and the year of admission. Data demonstrate the robust characteristics of the frailty index. The consistent association between frailty and dementia in long-term care over the decade has implications for integrated management strategies to delay frailty and dementia trajectories among at-risk residents.

The Effect of Low-Dose Aspirin on Frailty Phenotype and Frailty Index in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly Study.

Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.

Frailty and Depression in Late Life: A High-Risk Comorbidity With Distinctive Clinical Presentation and Poor Antidepressant Response.

To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score <10), and frailty (non/intermediate frail [0-2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.