Neighborhood Socioeconomic Deprivation and Health Care Costs in Older Community-Dwelling Adults: Importance of Functional Impairment and Frailty.

BACKGROUND: Low neighborhood socioeconomic status is associated with adverse health outcomes, but its association with health care costs in older adults is uncertain. OBJECTIVES: To estimate the association of neighborhood Area Deprivation Index (ADI) with total, inpatient, outpatient, skilled nursing facility (SNF), and home health care (HHC) costs among older community-dwelling Medicare beneficiaries, and determine whether these associations are explained by multimorbidity, phenotypic frailty, or functional impairments. DESIGN: Four prospective cohort studies linked with each other and with Medicare claims. PARTICIPANTS: In total, 8165 community-dwelling fee-for-service beneficiaries (mean age 79.2 years, 52.9% female). MAIN MEASURES: ADI of participant residence census tract, Hierarchical Conditions Category multimorbidity score, self-reported functional impairments (difficulty performing four activities of daily living), and frailty phenotype. Total, inpatient, outpatient, post-acute SNF, and HHC costs (US 2020 dollars) for 36 months after the index examination. KEY RESULTS: Mean incremental annualized total health care costs adjusted for age, race/ethnicity, and sex increased with ADI ($3317 [95% CI 1274 to 5360] for the most deprived vs least deprived ADI quintile, and overall p-value for ADI variable 0.009). The incremental cost for the most deprived vs least deprived ADI quintile was increasingly attenuated after separate adjustment for multimorbidity ($2407 [95% CI 416 to 4398], overall ADI p-value 0.066), frailty phenotype ($1962 [95% CI 11 to 3913], overall ADI p-value 0.22), or functional impairments ($1246 [95% CI -706 to 3198], overall ADI p-value 0.29). CONCLUSIONS: Total health care costs are higher for older community-dwelling Medicare beneficiaries residing in the most socioeconomically deprived areas compared to the least deprived areas. This association was not significant after accounting for the higher prevalence of phenotypic frailty and functional impairments among residents of socioeconomically deprived neighborhoods.

Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology.

Answer questions and earn CME/CNE The concept of frailty has become increasingly recognized as one of the most important issues in health care and health outcomes and is of particular importance in patients with cancer who are receiving treatment with surgery, chemotherapy, and radiotherapy. Because both cancer itself, as well as the therapies offered, can be significant additional stressors that challenge a patient's physiologic reserve, the incidence of frailty in older patients with cancer is especially high-it is estimated that over one-half of older patients with cancer have frailty or prefrailty. Defining frailty can be challenging, however. Put simply, frailty is a state of extreme vulnerability to stressors that leads to adverse health outcomes. In reality, frailty is a complex, multidimensional, and cyclical state of diminished physiologic reserve that results in decreased resiliency and adaptive capacity and increased vulnerability to stressors. In addition, over 70 different measures of frailty have been proposed. Still, it has been demonstrated that frail patients are at increased risk of postoperative complications, chemotherapy intolerance, disease progression, and death. Although international standardization of frailty cutoff points are needed, continued efforts by oncology physicians and surgeons to identify frailty and promote multidisciplinary decision making will help to develop more individualized management strategies and optimize care for patients with cancer. CA Cancer J Clin 2017;67:362-377. © 2017 American Cancer Society.

Indoor air pollution and frailty: A cross-sectional and follow-up study among older Chinese adults.

BACKGROUND: Previous studies have suggested that ambient air pollution negatively affects frailty, but whether indoor air pollution exposure affects frailty is unknown. METHOD: This study was conducted on 4946 older adults (≥60 years) followed from baseline to 4 years in the Chinese Longitudinal Healthy Longevity Survey. Household fuel types and frailty were assessed with self-rated questionnaires and physical examination. The relationships between indoor air pollution and frailty via phenotypic frailty and a frailty index were explored with logistic regression models and Cox proportional hazard regression models in both a cross-sectional and follow-up design. Additionally, the effects of indoor air pollution on phenotypic frailty together with mild cognitive impairment (MCI) were further investigated. RESULTS: In the cross-sectional study, the adjusted ORs (95% CIs) for frailty assessment with the frailty index and phenotypic frailty were 1.28 (1.12, 1.46) and 1.36 (1.18, 1.57), respectively. Solid fuel use was a risk factor in prefrail/frail patients with [OR and 95% CI, 1.88 (1.41, 2.50)], or without MCI [OR and 95% CI, 1.37 (1.17, 1.61)], as compared with the groups with no phenotypic prefrailty/frailty and no MCI. Moreover, solid cooking fuel use was positively associated with the incidence of phenotypic prefrailty and frailty. The adjusted HRs (95% CIs) for phenotypic prefrailty and frailty were 1.26 (1.03, 1.55). CONCLUSIONS: Solid cooking fuels can be regarded as a risk factor for frailty. Moreover, our findings suggest that more attention should be paid to solid cooking fuel using as it relates to phenotypic frailty together with MCI.

Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.

Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.

Lower muscle mitochondrial energetics is associated with greater phenotypic frailty in older women and men: the Study of Muscle, Mobility and Aging.

BACKGROUND: Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. METHODS: The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATPmax) in vivo, while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOSCI+CII). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. RESULTS: One-SD decrements of most respirometry measures (e.g., Max OXPHOSCI+CII, adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATPmax with frailty were weaker than those between Max OXPHOSCI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. CONCLUSIONS: Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study.

PURPOSE: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). MATERIALS AND METHODS: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. RESULTS: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). CONCLUSION: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

The Role of Neuropsychological Factors in Perceived Threat of SARS-CoV-2 in Healthy Ageing.

The COVID-19 pandemic is known to increase older adults' vulnerability to adverse outcomes. Alongside increased physical frailty, anxiety symptoms associated with the risk of SARS-CoV-2 contagion appear to represent its most prominent 'sequelae'. The attentional and linguistic resources required for decoding virus-related information may also influence the perceived threat of contagion. However, the possible role of neuropsychogeriatric factors on the latter dimension has never been assessed in a longitudinal study on the older population. To fill this gap, 50 healthy cognitively preserved older adults underwent a neuropsychological and physical frailty assessment before the pandemic (T0). Subsequently, they agreed to be interviewed and re-assessed during the lockdown (T1) and immediately after it (T2) through a longitudinal one-year study. Perceived threat of SARS-CoV-2 at T2 was predicted both by baseline anxiety and frailty scores, and by decreased performance in information processing speed and language comprehension tests. While confirming the joint role of frailty and anxiety, a moderation/interaction model showed that each of them was sufficient, at its highest level, to support the maximum degree of perceived threat of contagion. The contribution of neuropsychological factors to perceived threat of SARS-CoV-2 highlights their importance of tailoring information campaigns addressed to older people.

Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease.

Alzheimer's disease patients (AD), as well as AD transgenic mice, are characterized by increased frailty. Furthermore, the assessment of frailty status represents a feasible approach for detecting individuals prone to develop more severe form of AD and for measuring the outcome of existing and putative AD therapeutics. The 5xFAD mouse is one of the widely used transgenic animal models of AD, but frailty in this model is scantly investigated. We used two validated mouse frailty assessment tools: phenotypic frailty score (FS) and clinical frailty index (FI) to investigate age- and sex- related differences in frailty status in 5xFAD mice. These tools measure different age-related deficits and do not necessarily identify the same subpopulations as frail. We detected a significant increase in frailty with age in both sexes, although females were surprisingly less frail than males. Depending on the tools used, a notable difference in frailty status was detected, with frailty index and frailty score identifying different mice as frail. These results warrant great caution when choosing the frailty tool and point to the need for further adaptation of frailty measurements in mouse models of AD.

Hericium erinaceus Improves Recognition Memory and Induces Hippocampal and Cerebellar Neurogenesis in Frail Mice during Aging.

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, implicated in both poor quality of life and negative health outcomes. One central question surrounding frailty is whether phenotypic frailty is associated with the cognitive impairment during aging. Using spontaneous behavioral tests and by studying the dynamic change during aging, we demonstrated that the two form of vulnerability, locomotor and recognition memory decline, develop in parallel and therefore, integration of the motoric and cognitive evaluations are imperative. We developed an integrated frailty index based on both phenotypic and recognition memory performances. Hericium erinaceus (H. erinaceus) is a medicinal mushroom that improves recognition memory in mice. By using HPLC-UV-ESI/MS analyses we obtained standardized amounts of erinacine A and hericenones C and D in H. erinaceus extracts, that were tested in our animal model of physiological aging. Two-month oral supplementation with H. erinaceus reversed the age-decline of recognition memory. Proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunohistochemistry in the hippocampus and cerebellum in treated mice supported a positive effect of an H. erinaceus on neurogenesis in frail mice.

Modifying the Phenotypic Frailty Model in Predicting Risk of Major Osteoporotic Fracture in the Elderly.

INTRODUCTION: The phenotypic frailty (PF) model (including slow walking, low physical activity, exhaustion, weakness, and unintentional weight loss) has been widely used to quantify the degree of frailty and predict risks of adverse health outcomes for the elderly. However, evidence has shown that not all the components included in the PF model contribute equally, and low predictive accuracy of the PF model has been reported in predicting risks of outcomes. We aimed to improve predictive accuracy of the PF model in risk of major osteoporotic fracture (MOF) in the elderly by modifying its weighting of individual components. METHODS: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort were used for this study. We used the multivariable Cox regression model to identify the updated weighting for components in the original PF model. The goodness of fit and discrimination were assessed for model performances. RESULTS: There were 3985 women included for analyses (mean age: 69.4 years). In the modified PF model, the updated weighting was 3 points for slowness and weakness, 2 points for weight loss, 1 point for poor endurance and exhaustion, and 1 point for low physical activity, respectively. The modified PF model could capture and categorize the future risk of MOF more accurately than the original model. Significant relationship between risks of MOF, falls, and death and the modified PF model was found. Compared with the original model, the modified PF model was a better fit to the data and with improved predictive accuracy. CONCLUSION: Based on a simple and practical rescoring and recategorizing algorithm, the modified PF model could predict risks of adverse outcomes more accurately than the original model, reflecting a cost-effective way. More evidence is needed to validate the modified PF model and support its application in geriatric practice.