Intrinsic Capacity as a Determinant of Physical Resilience in Older Adults.

The traditional disease-oriented model of healthcare is inadequate to address the needs of the older population. Greater attention should be given to strategies that promote healthy aging. Recently proposed constructs of intrinsic capacity (IC) and physical resilience (PR) hold great potential to reshape geriatric medicine and aging research. These constructs accentuate the positive health attributes of older people in contrast to the popular frailty construct that is centered on functional deficits. IC was introduced by the World Health Organization (WHO) as a composite of all the physical and mental capacities. WHO has emphasized enhancement of IC throughout the life course so as to maintain functional ability in old age. PR, recently highlighted by the National Institute on Aging, is the ability to successfully cope with stressors. High levels of resilience can result in desirable clinical and functional outcomes after stressors. Therefore, it is important to understand the underlying physiology of PR and the risk factors contributing to diminished PR. The main goal of this article is to explore the potential relationship between IC and PR. Based on a classical theory of aging, we postulate that IC is a determinant of PR and is also a high-level integrative measure of physiologic reserve which is the fundamental factor underlying one's ability to withstand stressors. A major implication of our postulates is that even though IC is only one of the many determinants of PR, it could serve as an important intervenable target for enhancing resilience in older adults.

Relationship of Physical Frailty to Phosphocreatine Recovery in Muscle after Mild Exercise Stress in the Oldest-Old Women.

BACKGROUND: Physical frailty is a clinical syndrome associated with aging and manifesting as slowness, weakness, reduced physical activity, weight loss, and/or exhaustion. Frail older adults often report that their major problem is "low energy", and there is indirect evidence to support the hypothesis that frailty is a syndrome of dysregulated energetics. We hypothesized that altered cellular energy production underlies compromised response to stressors in the frail. METHODS: We conducted a pilot study to assess muscle energetics in response to a mild isometric exercise challenge in women (n=30) ages 84-93 years. The frailty status was assessed by a validated physical frailty instrument. Localized phosphorus (P31) magnetic resonance spectroscopy with a 1.5T magnet was used to assess the kinetics of Phosphocreatine recovery in the tibialis anterior muscle following maximal isometric contraction for 30 seconds. RESULTS: Phosphocreatine recovery following exertion, age-adjusted, was slowest in the frail group (mean=189 sec; 95%CI: 150,228) compared to pre-frail (mean=152 sec; 95%CI: 107,197) and nonfrail subjects (mean=132 sec; 95%CI: 40,224). The pre-frail and frail groups had 20 sec (95%CI: -49,89) and 57 sec (95%CI: -31,147) slower phosphocreatine recovery, respectively, than the non-frail. This response was paralleled by dysregulation in glucose recovery in response to oral glucose tolerance test in women from the same study population. CONCLUSIONS: Impaired muscle energetics and energy metabolism might be implicated in the physical frailty syndrome.

The Use of Figurative Language to Describe Frailty in Older Adults.

INTRODUCTION: Frailty affects 15% of non-institutionalized older adults in the United States, yet confusion remains in defining and, in turn, assessing frailty. Figurative language, such as metaphor, can help to explain difficult scientific concepts and to form new theories. We aimed to examine the use of figurative language to describe frailty and to identify themes in the way figurative expressions are used. Understanding how frailty is described figuratively may offer insights for developing useful communication approaches in research settings. METHODS: We performed a comprehensive review of editorials in the scientific literature to explore figurative language used to describe frailty in older adults. We categorized themes among the figurative expressions, which may help to inform how to effectively communicate about frailty. RESULTS: We found 24 editorials containing 32 figurative expressions. The figurative expressions conceptualized frailty in six ways: 1) a complex, multifaceted concept; 2) an important issue in health and medicine; 3) indicative of something that is failing or faulty; 4) indicative of fragility; 5) representative of vulnerable, ignored persons; and 6) an opportunity for self-awareness and reflection. DISCUSSION: Our review highlights the heterogeneity in depictions of frailty, which is consonant with the lack of a standardized definition of frailty. We also found a novel aspect to the concept of frailty, which merits attention: frailty characterized as an opportunity for self-awareness and reflection. Figurative language, which often juxtaposes familiar with challenging, complex concepts, can offer insights on issues in frailty research and holds potential as a tool for researchers to improve communication about this important and debated medical condition.

Frailty and mortality in kidney transplant recipients.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women.

OBJECTIVES: Frailty status is associated with altered glucose-insulin dynamics. Here, we sought to investigate whether alteration in the dynamics of other circulating energy metabolism hormones after oral glucose is associated with frailty status. DESIGN: Substudy of older women in a prospective cohort. SETTING: Baltimore, Maryland. PARTICIPANTS: Seventy-three community-dwelling women aged 84-95 years without a diagnosis of diabetes who were enrolled in the Women's Health and Aging Study II. MEASUREMENTS: We examined stimulus-response dynamics of free fatty acids (FFA), gut- (ghrelin,GLP-1) and adipocyte-derived hormones (leptin, adiponectin, resistin), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6) at 0, 30, 60, 120, and 180-minutes after a 75-g glucose challenge according to frailty status (non-frail, pre-frail, or frail). RESULTS: On average, frail women had higher fasting levels of glucose-raising hormones (FFA, resistin, GH, and IL-6) and lower fasting levels of glucose-lowering hormones (ghrelin, adiponectin, GLP-1 and IGF-1) versus non-frail women but these results were not statistically significant. Frail women also had higher fasting levels of leptin with relative adiposity compared to their counterparts, suggestive of leptin-resistance. Integrated area under the curve (AUC) values for each hormone followed similar trends by frailty status. After age and BMI adjustment, frail versus non-frail women were more likely to be in the lowest tertile of fasting ghrelin levels and 120-min ghrelin levels (both p<0.05) in logistic regression analyses. No large differences were found for other hormones in adjusted models. CONCLUSIONS: Our findings suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome. Further studies are needed to explore the role of ghrelin dysregulation in the clinical manifestation of frailty.

Relationship of a dominant advanced glycation end product, serum carboxymethyl-lysine, and abnormal glucose metabolism in adults: the Baltimore Longitudinal Study of Aging.

BACKGROUND AND OBJECTIVES: Although hyperglycemia is thought to increase the generation of advanced glycation end products (AGEs), studies have not shown a consistent relationship between abnormal glucose metabolism and serum AGEs. We investigated the relationship between a dominant serum AGE, N-carboxymethyl-lysine (CML), and glucose metabolism. SUBJECTS AND METHODS: Serum CML, fasting plasma glucose, and glucose tolerance were measured in 755 adults in the Baltimore Longitudinal Study of Aging. Fasting plasma glucose was categorized as normal (< or = 99 mg/dL), impaired (100-125 mg/dL), and diabetic (> 125 mg/dL). Two-hour plasma glucose on oral glucose tolerance testing was categorized as normal (< or = 139 mg/dL), impaired (140-199 mg/dL), and diabetic (> or = 200 mg/dL). RESULTS: The proportion of adults with normal, impaired, and diabetic fasting plasma glucose was 73.8%, 22.9%, and 2.9%, respectively, and the proportion with normal, impaired, and diabetic 2-hour plasma glucose was 73.1%, 19.2%, and 7.7%, respectively. Serum CML (microg/mL) was not associated with abnormal fasting plasma glucose (Odds Ratio [O.R.] 0.60, 95% Confidence Interval [C.I.] 0.15-2.36, P = 0.47) in a multivariate, ordered logistic regression model, adjusting for age, race, gender, body mass index, and chronic diseases. Serum CML (microg/mL) was associated with abnormal 2-hour plasma glucose on glucose tolerance testing (O.R. 0.15, 95% C.I. 0.04-0.63, P = 0.009) in a multivariate, ordered logistic regression model, adjusting for the same covariates. CONCLUSIONS: Elevated CML, a dominant AGE, was not associated with elevated fasting plasma glucose and was associated with a reduced odds of abnormal glucose tolerance in older community-dwelling adults.

Low serum carotenoids are associated with a decline in walking speed in older women.

BACKGROUND AND OBJECTIVES: Walking speed is an important measure of physical performance that is predictive of disability and mortality. The relationship of dietary factors to changes in physical performance has not been well characterized in older adults. The aim was to determine whether total serum carotenoid concentrations, a marker for fruit and vegetable intake, and serum selenium are related to changes in walking speed in older women. SUBJECTS AND METHODS: The relationship between total serum carotenoids and selenium measured at baseline, 12, and 24 months follow-up and walking speed assessed at baseline and every six months for 36 months was examined in 687 moderately to severely disabled women, 65 years or older, living in the community. RESULTS: Mean total serum carotenoids were associated with mean walking speed over three years of follow-up (P = 0.0003) and rate of change of walking speed (P = 0.007) in multivariate linear regression models adjusting for age, body mass index, and chronic diseases. Mean serum selenium was associated with mean walking speed over three years of follow-up (P = 0.0003) but not with the rate of change of walking speed (P = 0.26). CONCLUSIONS: These findings suggest that a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women.

Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty.

Frailty is a state of health signified by an increased vulnerability to adverse health outcomes in the face of stressors (e.g. infection). There is emerging consensus that research on both the theory and measurement of frailty must focus on the dynamic interactions within and across systems underlying the frailty syndrome. In this paper, we propose a dynamical systems modeling approach, based on the stimulus-response experimental paradigm, to propel future advances in the study of frailty. Our proposal is novel in that it provides a quantitative framework to operationalize and test the core notion underlying frailty that it signifies a loss of resilience in homeostatic regulation. The proposed framework offers many important benefits, including (a) insights into whether and how homeostatic regulation differs between frail and non-frail older adults, (b) identification of critical regulatory systems, if they exist, that could function as sentinel systems for screening and early detection of frailty, (c) establishment of the value of provocative tests that can provide maximal information on the integrity of systems identified in (b), and (d) evaluation and unification of diverse empirical descriptions of frailty by providing a mathematical framework anchored in quantifying the loss of resilience, an essential property of frailty.

The use of angiotensin-converting enzyme inhibitors and diuretics is associated with a reduced incidence of impairment on cognition in elderly women.

The effects of angiotensin-converting enzyme inhibitors (ACE-Is) and diuretics (used as antihypertensive agents) on global and domain-specific cognitive decline were evaluated in 326 non-demented community-dwelling participants over the age of 70 years in the Women's Health and Aging Study II. Time-dependent Cox proportional hazards regression analysis was used for evaluating the association between parameters. The use of ACE-I for more than 3 years was associated with reduced incidence of impairment on Mini-Mental State Examination (MMSE), Trail Making Test-Part A and Part B (TMT, Parts A and B), Hopkins Verbal Learning Test-Immediate Recall (HVLT-I), and Hopkins Verbal Learning Test-Delayed Recall (HVLT-D). The use of diuretics for more than 3 years was associated with reduced incidence of impairment on MMSE, TMT, Parts A and B, HVLT-I, and (HVLT-D). The presence of vascular disease did not make any difference to these effects. Therefore, the use of ACE-Is or diuretics was associated with reduced incidence of impairment of both global and domain-specific cognition in elderly women, and may help delay progression to dementia.