Background: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. 

Methods: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. 

Results: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). 

Conclusions: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

https://www.sharp.com/services/hospice/upload/phenotype5-13.pdf

Frailty in Older Adults Evidence for a Phenotype

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Cardiovascular Health Study Collaborative Research Group : Frailty in older adults : evidence for a phenotype

The R package mice imputes incomplete multivariate data by chained equations. The software mice 1.0 appeared in the year 2000 as an S-PLUS library, and in 2001 as an R package. mice 1.0 introduced predictor selection, passive imputation and automatic pooling. This article documents mice, which extends the functionality of mice 1.0 in several ways. In mice, the analysis of imputed data is made completely general, whereas the range of models under which pooling works is substantially extended. mice adds new functionality for imputing multilevel data, automatic predictor selection, data handling, post-processing imputed values, specialized pooling routines, model selection tools, and diagnostic graphs. Imputation of categorical data is improved in order to bypass problems caused by perfect prediction. Special attention is paid to transformations, sum scores, indices and interactions using passive imputation, and to the proper setup of the predictor matrix. mice can be downloaded from the Comprehensive R Archive Network. This article provides a hands-on, stepwise approach to solve applied incomplete data problems.

/pdf/mice-multivariate-imputation-by-chained-equations-in-r-2cffzza5jj.pdf

mice: Multivariate Imputation by Chained Equations in R

The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.

/pdf/sarcopenia-european-consensus-on-definition-and-diagnosis-2axty2moc3.pdf

Sarcopenia: European consensus on definition and diagnosis Report of the European Working Group on Sarcopenia in Older People

ABSTRACT Introduction Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation—a pathway often underlying frailty—remains unexplored. Methods Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined. Results Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d−1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% (P = 0.003), 13% (P = 0.001), and 8% (P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all). Conclusions Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal.

Patterns of Daily Physical Movement, Chronic Inflammation, and Frailty Incidence

The invention described herein provides methods for treating a disease or disorder associated with angiotensin receptor signaling in a patient exhibiting elevated levels of ATIR autoantibodies. The invention also provides methods of identifying a patient suffering from a disease or disorder associated with angiotensin receptor signaling that may benefit from treatment with an angiotensin receptor blocker. Patients with elevated levels of ATIR autoantibodies are identified as candidates that particularly benefit from treatment with an angiotensin receptor blocker.

Angiotensin receptor autoantibodies as biomarker for effective usage of angiotensin receptor blockers

Chronic inflammation, oxidative stress, and dysregulation of the renin-angiotensin system are closely linked, and their crosstalk commonly contributes to age-related physical and cognitive decline. The primary dementia-protective benefits of Angiotensin II receptor type 1 (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, there is an independently regulated brain-specific renin-angiotensin system. Here, we examined the impact of 4 weeks of oral Losartan treatment on the brains of aged (100 weeks old) IL-10 -/- mice, an animal model of chronic inflammation and frailty. Our data show that aged IL-10 -/- mice have higher AT1R and Nitrotyrosine (oxidative stress marker) levels in their frontal cortex tissue but not in cerebellar or hippocampal tissue compared to age- and sex-matched wild type mice. Losartan treatment for four weeks is associated with lower AT1R protein level, Nitrotyrosine, and Tau protein in the frontal cortex of aged IL-10 -/- mice. Our results highlight the impact of Losartan, an AT1R blocker commonly prescribed for treating high blood pressure, on the brain-specific angiotensin system and AT1R-linked downstream effects such as brain oxidative stress damage and Tau burden in a frailty mouse model.

Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL10 -/- Mice.

Abstract End-stage renal disease (ESRD) causes age-accelerating disease and disproportionally affects older and minority patients; the preferred treatment is kidney transplantation (KT). Rates of KT have risen 5-fold for older adults since 1990 but there is great heterogeneity in KT outcomes by frailty and waitlist status. The person-environment fit theory posits that improving a person’s lived environment will facilitate optimal individual functioning. We recruited a balanced sample of 20 participants (mean age 60, range 35-82) with respect to their frail/ pre-frail and inactive/ active waitlist status to explore personal experience and the lived environment through the use of photovoice, gaining insight into the person-environment fit of those older adults awaiting KT. We will discuss IRB issues, recruitment and logistical tips with using Photovoice. This work will help to inform what vulnerable and marginalized older adults awaiting KT must be prepared for psychologically and physically, including modifications needed to their lived environments.

Jeremy D. Walston

Papers

Patterns of Daily Physical Movement, Chronic Inflammation, and Frailty Incidence

Angiotensin receptor autoantibodies as biomarker for effective usage of angiotensin receptor blockers

Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL10 -/- Mice.

Using photovoice to understand the lived experience and environment of older adults awaiting kidney transplant

African-Americans and Caucasians Total daily energy expenditure in free-living older