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.

Mental distress and its associations with behavioral outcomes during the COVID-19 pandemic: a national survey of Chinese adults.

OBJECTIVES: This study aimed to evaluate associations between mental distress and COVID-19-related changes in behavioral outcomes and potential modifiers (age, gender, educational attainment) of such associations. STUDY DESIGN: This was a cross-sectional study. METHODS: An online survey using anonymous network sampling was conducted in China from April to May 2020 using a 74-item questionnaire. A national sample of 10,545 adults in 31 provinces provided data on sociodemographic characteristics, COVID-19-related mental distress, and changes in behavioral outcomes. Structural equation models were used for data analyses. RESULTS: After adjusting for covariates, greater mental distress was associated with increased smoking (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.20-1.68 and OR = 1.54, 95% CI: 1.31-1.82 per one standard deviation [SD] increase in mental distress) and alcohol consumption (OR = 1.67, 95% CI: 1.45-1.92 and OR = 1.47, 95% CI: 1.24-1.75 per one SD increase in mental distress) among current smokers and drinkers and with both increased and decreased physical activity (ORs ranged from 1.32 to 1.56). Underweight adults were more likely to lose body weight (≥1 kg; OR = 1.63, 95% CI: 1.30-2.04), whereas overweight adults were more likely to gain weight (OR = 1.61, 95% CI: 1.46-1.78) by the same amount. Association between mental distress and change in physical activity was stronger in adults aged ≥40 years (ORs ranged from 1.43 to 2.05) and those with high education (ORs ranged from 1.43 to 1.77). Mental distress was associated with increased smoking in males (OR = 1.60, 95% CI: 1.37-1.87) but not females (OR = 1.11, 95% CI: 0.82-1.51). CONCLUSIONS: Greater mental distress was associated with some positive and negative changes in behavioral outcomes during the pandemic. These findings inform the design of tailored public health interventions aimed to mitigate long-term negative consequences of mental distress on outcomes.

Lactoferrin for the treatment of age-associated inflammation - A pilot study.

BACKGROUND: Chronic inflammation (CI) is a common trait of aging associated with adverse outcomes including mortality. We hypothesized that recombinant human Lactoferrin (rhLf) would reduce chronic inflammation of aging. METHODS: Thirty-six community dwelling older adults were randomly assigned to rhLf or placebo treatment in 1:1 ratio for 3 months. IL-6, sTNFR1, Comprehensive Metabolic Panel (CMP), and Complete Blood Count (CBC) were measured at baseline, 1 month, 3 months, and 6 months. Physical and cognitive measures were completed at same timepoints, including 4-m walking speed (m/s), grip strength (kg), 6-min walking distance (m), home activity measured by accelerometer, trail making test - Part A (s) and - Part B (s), and Digit symbol substitution test (number correctly coded). Primary outcomes were differences in IL-6 and sTNFR1 concentrations evaluated by generalized linear model with log-link and gamma family distribution, controlling for baseline cytokine concentrations. RESULTS: rhLF was well-tolerated. There were a significant number of abdominal complaints and increased drop-out rate in placebo group. Participants in rhLf arm had non-significant lower mean percent increase in IL6 at 3 months (rhLf mean IL-6 6% lower than control, P = 0.843), and sTNFaR1 (rhLf mean 2% lower than control, P = 0.36). No significant changes were observed for the cognitive or physical measures. CONCLUSION: Treatment with rhLf did not significantly alter serum IL6 or sTNFR1 concentrations of older adults. This study may have been underpowered to detect difference, but provided evidence that a larger sample-size could more definitively determine the effect of rhLF on age-associated CI.

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 association of neighborhood characteristics with obesity and metabolic conditions in older women.

OBJECTIVE: Previous studies exploring the relationship of neighborhood characteristics with metabolic conditions have focused on middle-aged adults but none have comprehensively investigated associations in older adults, a potentially vulnerable population. The aim was to explore the relationship of neighborhood characteristics with metabolic conditions in older women. DESIGN: Cross-sectional analysis. SETTING/PARTICIPANTS: We studied 384 women aged 70-79 years, representing the two-thirds least disabled women in the community, enrolled in the Women's Health and Aging Study II at baseline. Neighborhood scores were calculated from census-derived data on median household income, median house value, percent earning interest income, percent completing high school, percent completing college, and percent with managerial or executive occupation. Participants were categorized by quartile of neighborhood score with a higher quartile representing relative neighborhood advantage. Logistic regression models were created to assess the association of neighborhood quartiles to outcomes, adjusting for key covariates. MEASUREMENTS: Primary outcomes included metabolic conditions: obesity, diabetes, hypertension, and hyperlipidemia. Secondary outcomes included BMI, HbA1c, blood pressure and lipids. RESULTS: Higher neighborhood quartile score was associated with a lower prevalence of obesity (highest quartile=13.5% versus lowest quartile=36.5%; p<0.001 for trend). A lower prevalence of diabetes was also observed in highest (6.3%) versus lowest (14.4%) neighborhood quartiles, but was not significantly different (p= 0.24 for trend). Highest versus lowest neighborhood quartile was associated with lower HbA1c (-0.31%, p=0.02) in unadjusted models. Women in the highest versus lowest neighborhood quartile had lower BMI (-2.01 kg/m2, p=0.001) and higher HDL-cholesterol (+6.09 mg/dL, p=0.01) after accounting for age, race, inflammation, and smoking. CONCLUSION: Worse neighborhood characteristics are associated with adiposity, hyperglycemia, and low HDL. Further longitudinal studies are needed and can inform future interventions to improve metabolic status in older adults.

The association of genetic variants in interleukin-1 genes with cognition: findings from the cardiovascular health study.

The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.

Low serum selenium is associated with anemia among older adults in the United States.

OBJECTIVE: We hypothesized that low serum selenium was associated with anemia in humans. SUBJECTS: A total of 2092 adults aged 65 and older, in the third National Nutrition Examination Survey, Phase 2 (1991-1994) (NHANES III). METHODS: Examination of the relationship between serum selenium and hematological indices in NHANES III. RESULTS: Anemia, defined by World Health Organization criteria, was present in 12.9%. Mean serum selenium among non-anemic and anemic adults was 1.60 and 1.51 micromol l(-1) (P=0.0003). The prevalence of anemia among adults in the lowest to highest quartiles of serum selenium was 18.3, 9.5, 9.7 and 6.9%, respectively (P=0.0005). The proportion of adults in the lowest quartile of selenium among those who were non-anemic or who had anemia due to nutritional causes, chronic inflammation, renal disease or unexplained anemia was 9.9, 27.5, 17.5, 24.0 and 15.4%, respectively. An increase in log(e) selenium was associated with a reduced risk of anemia (odds ratio per one standard deviation increase 0.75, 95% confidence interval 0.58-0.97, P=0.03), adjusting for age, race, education, body mass index and chronic diseases. CONCLUSION: Low serum selenium is independently associated with anemia among older men and women in the United States.

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.

Denture use, malnutrition, frailty, and mortality among older women living in the community.

BACKGROUND: The relationships between denture use, malnutrition, frailty, and mortality in older women have not been well characterized. OBJECTIVE: To determine whether women who use dentures and have difficulty chewing or swallowing are at higher risk of malnutrition, frailty, and mortality. DESIGN: Cross-sectional and longitudinal study of 826 women, aged 70-79, from the Women's Health and Aging Studies, two population-based longitudinal studies of community-dwelling women in Baltimore, Maryland. At enrollment, data on frailty and self-reported denture use and difficulty chewing or swallowing that limited the ability to eat was collected, and plasma vitamins A, D, E, B6, and B12, carotenoids, folate, and albumin were measured. RESULTS: 63.5% of women reported using dentures, of whom 11.6% reported difficulty chewing or swallowing food. Denture users with and without difficulty chewing or swallowing and those not using dentures had, respectively, geometric mean (95% Confidence Interval [C.I.]) total plasma carotenoid concentrations of 1.481 (1.302, 1.684), 1.616 (1.535, 1.700), and 1.840 (1.728, 1.958) micromol/L, respectively (P < 0.0001), and 25- hydroxyvitamin D of 50.90 (44.25, 58.55), 47.46 (45.15, 50.40), and 54.0 (50.9, 56.8) nmol/L (P < 0.0001). The proportion using dentures among non-frail, pre-frail, and frail women was 58%, 66%, and 73%, respectively (P = 0.018). Women who used dentures and reported difficulty chewing or swallowing had lower five-year survival (H.R. 1.43, 95% C.I. 1.05-1.97), after adjusting for potential confounders. CONCLUSIONS: Older women living in the community who use dentures and have difficulty chewing or swallowing have a higher risk of malnutrition, frailty, and mortality.

Diabetes, hyperglycaemia and mortality in disabled older women: The Women's Health and Ageing Study I.

AIMS: Diabetes is associated with increased mortality in older adults, but the specific contributions of diabetes-associated clinical conditions and of increasing hyperglycaemia to mortality risk are unknown. We evaluated whether cardiovascular disease, comorbidities, or degree of hyperglycaemia, particularly severe hyperglycaemia, affected diabetes-related mortality risk in older, disabled women. METHODS: Six-year mortality follow-up of a random sample of 576 disabled women (aged 65-101 years), recruited from the Medicare eligibility list in Baltimore (MD, USA). All-cause and cardiovascular mortality were evaluated by diabetes status: no diabetes; diabetes with mild, moderate, and severe hyperglycaemia [defined by tertiles of glycosylated haemoglobin (GHB) among women with diabetes]. RESULTS: Diabetes with mild, moderate, and severe hyperglycaemia was associated with an increased hazard rate (HR) for all-cause mortality, even after adjustment for demographics, risks for cardiovascular disease, cardiovascular and non-cardiovascular conditions, and other known mortality risks. A dose-response effect was suggested [mild hyperglycaemia, HR 1.81, 95% confidence interval (CI) 1.03, 3.17; moderate hyperglycaemia, HR 2.02, 95% CI 1.34, 3.57; severe hyperglycaemia, HR 2.22, 95% CI 1.17, 4.25]. Women with diabetes had a significantly increased HR for non-cardiovascular death, but not for cardiovascular death, compared with those without diabetes. CONCLUSIONS: Diabetes, whether characterized by mild, moderate or severe hyperglycaemia, appears to be an independent risk factor for excess mortality in older disabled women and this risk may increase with increasing hyperglycaemia. This mortality risk is not completely explained by vascular complications, and involves non-cardiovascular deaths. Risks and benefits of diabetes management, including glycaemic control and management of vascular and other comorbidities, should be studied in older people with complications and comorbidities.

Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women's Health and Aging Study II cohort.

OBJECTIVES: To determine whether polymorphic variation in the myostatin gene differentially influences the maintenance of muscle strength in older adults, and to find supportive evidence in a cohort of older women. DESIGN: Correlation study of polymorphic variation in a cohort of older women. SETTING: Representatively sampled older female population living in the eastern half of Baltimore, Maryland. PARTICIPANTS: Participants were 286 women, age 70 to 79. Of these, 81.1% were Caucasian, 18.8% were African American, and 0.2% were Asian or Hispanic. MEASUREMENTS: Overall strength was measured with a dynamometer and defined as the sum of the strongest measures of hip, knee, and grip strength on the dominant side. RESULTS: We identified or confirmed six myostatin polymorphic variants in the Women's Health and Aging Study II population. Of the polymorphisms, K153R is the most common, with an allele frequency of 0.19 in African Americans. Unadjusted mean strength by genotype suggested lower muscle strength in those African-American women with the R genotype compared with those with the K genotype (K/K: 72.50 +/- 13.9 kg (n = 39) vs K/R: 67.14 +/- 11.4 kg (n = 13) vs R/R: 63.1 +/- 11.3 kg (n = 3)). After adjustment for race in a linear regression model, the R genotype remained associated with lower strength levels (P = .04). Statistical significance decreased when body mass index and race were both added to the model (P = .09). CONCLUSIONS: Recognizing that small sample size in the study of genes of modest effect are unlikely to yield significant differences, these data suggest an association of the R153 allele with lower strength in high-functioning older women, which should be studied further in a larger cohort.

Association between executive attention and physical functional performance in community-dwelling older women.

OBJECTIVES: Executive functions supervise the contents of working memory, where information from long-term memory is integrated with information in the immediate present. This study examined whether executive attentional abilities were uniquely associated with the performance of complex, instrumental activities of daily living (IADLs) in cognitively intact and physically high-functioning older women. METHODS: Participants were 406 community-residing, older women aged 70-80 years in the Women's Health and Aging Study (WHAS) II, screened to be physically high functioning and cognitively intact using the Mini-Mental State Exam. Hierarchical regression models, adjusted for demographic and disease variables, were used to evaluate the association of cognitive domains, including executive attention, memory, psychomotor speed, and spatial ability with summary measures of IADL (e.g., looking up and dialing a telephone number) and mobility-based ADL (e.g., walking 4 meters) function. RESULTS: Tests of executive attention were associated with performance on IADLs (6.6%) and, to a lesser degree, mobility-based ADLs (1%), adjusting for demographic and disease variables. In particular, the mental flexibility component of the Trail Making Test accounted for the majority of attentional variance in IADL performance. Older age, lower education, and African American race were also associated with poorer physical test performances. DISCUSSION: Executive difficulties in flexibly planning and initiating a course of action were selectively associated with slower performance of higher-order IADL tests, relative to other domains of cognition, in a high-functioning, community-based older cohort. These results suggest that executive functions may be important in mediating the onset and progression of physical functional declines.