Quantifying Older Black Americans' Exposure to Structural Racial Discrimination: How Can We Measure the Water In Which We Swim?

The USA was built on legalized racism that started with enslavement and continues in the form of structural racial discrimination. This discrimination is difficult to measure because its many manifestations are hard to observe and dynamic. A useful tool would measure across settings, institutions, time periods in a person's life and the country's history. The purpose of this study was to design a measure of structural racial discrimination that meets those criteria and can be used in large national datasets. To do this, we started with an exploratory mixed-methods instrument design, including qualitative interviews with 15 older Black adults and focus groups with 38 discrimination researchers and other key stakeholders. We then identified 27 indicators of structural racial discrimination across nine theorized discrimination contexts. We matched these with historical administrative data sets to develop an instrument that could quantify older Black Americans' exposure to structural racial discrimination across contexts, the life course, and geographies. These can be mapped to the life course of structural discrimination based on the home addresses of those surveyed. Linking these to available indicators is a promising approach. It is a low burden for participants and enables increasingly multifaceted and focused measurement as more national datasets become available. A flexible, feasible comprehensive measure of structural discrimination could allow not only more thorough documentation of inequities but also allow informed decision making about policies and programs intended to promote racial equity. SIGNIFICANCE STATEMENT: To our knowledge, this is the first study that presents a framework for assessing structural racial discrimination across contexts, life course, and geography that is grounded in theory and in the lived experience of intended participants. Leading researchers and policy makers have called for improved measures of structural racism and discrimination and specifically for a lifecourse approach to measurement. This study is a step in that direction. CLASSIFICATION: Social Sciences.

The effect of missing data and imputation on the detection of bias in cognitive testing using differential item functioning methods.

BACKGROUND: Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. METHODS: We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. RESULTS: When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. CONCLUSIONS: Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.

Clinically Meaningful Change for Physical Performance: Perspectives of the ICFSR Task Force.

For clinical studies of sarcopenia and frailty, clinically meaningful outcome measures are needed to monitor disease progression, evaluate efficacy of interventions, and plan clinical trials. Physical performance measures including measures of gait speed and other aspects of mobility and strength have been used in many studies, although a definition of clinically meaningful change in performance has remained unclear. The International Conference on Frailty and Sarcopenia Research Task Force (ICFSR-TF), a group of academic and industry scientists investigating frailty and sarcopenia, met in Miami Beach, Florida, USA in February 2019 to explore approaches for establishing clinical meaningfulness in a manner aligned with regulatory authorities. They concluded that clinical meaningful change is contextually dependent, and that both anchor- based and distribution-based methods of quantifying physical function are informative and should be evaluated relative to patient-reported outcomes. In addition, they identified additional research needed to enable setting criteria for clinical meaningful change in trials.

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.

Longitudinal evaluation of clustering of chronic sinonasal and related symptoms using exploratory factor analysis.

BACKGROUND: Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis (CRS). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors. METHODS: We used questionnaire responses to 37 questions on the presence, severity, bother, and frequency of cardinal sinonasal and related symptoms lasting 3 months, from 3535 subjects at 3 time points over 16 months. We completed 5 exploratory factor analyses (EFA) to identify symptom clustering, 1 for each time point and 2 for the differences between adjacent questionnaires. The baseline EFA was used to provide factor scores that were described longitudinally and examined by CRS status. RESULTS: Five EFAs identified the same 5 factors (blockage and discharge, pain and pressure, asthma and cold/flu symptoms, smell loss, and ear and eye [mainly allergy] symptoms), with clustering determined by symptom frequency, severity, and degree of bother. Responses to individual questions showed changes over time but when combined into factor scores showed less longitudinal change. All symptom factor scores were progressively higher from never to past to current CRS status. CONCLUSIONS: Although the current approaches to symptom characterization in CRS imply a single underlying latent construct, our results suggest that there are at least 3 latent constructs relevant to CRS. Further studies are needed to evaluate whether these clusters have identifiable underlying pathobiologies.

Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus symptoms by chronic rhinosinusitis status.

BACKGROUND: Nasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS). METHODS: Four seasonal questionnaires were mailed to a stratified random sample of Geisinger primary care patients. Logistic regression was used to identify individual characteristics associated with AENSS occurrence and severity by CRS status (current long-term, current recent, past, never) using EPOS subjective symptoms-only (EPOSS ) CRS criteria. We operationalized 3 AENSS definitions based on prescribed antibiotics or oral corticosteroids, symptoms, and symptoms with purulence. RESULTS: Baseline and at least 1 follow-up questionnaires were available from 4736 subjects. Self-reported NSS severity with exacerbation was worst in the current long-term CRS group. AENSS was common in all subgroups examined and generally more common among those with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition and CRS status. Associations of risk factors with AENSS differed by definition, but CRS status, body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicted AENSS. CONCLUSIONS: In this first longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOSS CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS.

On pseudolikelihood inference for semiparametric models with boundary problems.

Consider a semiparametric model indexed by a Euclidean parameter of interest and an infinite-dimensional nuisance parameter. In many applications, pseudolikelihood provides a convenient way to infer the parameter of interest, where the nuisance parameter is replaced by a consistent estimator. The purpose of this paper is to establish the asymptotic behaviour of the pseudolikelihood ratio statistic under semiparametric models. In particular, we consider testing the hypothesis that the parameter of interest lies on the boundary of its parameter space. Under regularity conditions, we establish the equivalence between the asymptotic distributions of the pseudolikelihood ratio statistic and a likelihood ratio statistic for a normal mean problem with a misspecified covariance matrix. This result holds when the nuisance parameter is estimated at a rate slower than the usual rate in parametric models. We study three examples in which the asymptotic distributions are shown to be mixtures of chi-squared variables. We conduct simulation studies to examine the finite-sample performance of the pseudolikelihood ratio test.

Antibiotic use and childhood body mass index trajectory.

BACKGROUND/OBJECTIVES: Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children. SUBJECTS/METHODS: We used electronic health record data on 163 820 children aged 3-18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations-reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj) and progressive (cumulative orders up to prior BMI (BMIj-1))-and whether these varied by age. RESULTS: Among 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use. CONCLUSIONS: We found evidence of reversible, persistent and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.

Diet quality and social support: factors associated with serum carotenoid concentrations among older disabled women (the Women's Health and Aging Study).

PURPOSE: This study investigated the relationship between social support (including instrumental support, emotional support, social interaction, social space, and family networks) and diet quality, as indicated by serum carotenoid levels. DESIGN AND METHODS: The sample consisted of participants in the Women's Health and Aging Study with longitudinal carotenoid data (n=325). We performed regression analyses using baseline indicators of social support and changes in social support to determine whether baseline levels and/or change in levels of social support predict changes in serum carotenoid levels. Social support changes were measured over 1 year from baseline to follow-up round 1. Carotenoid level changes were established from follow-up round 1 to round 2. To determine whether or not regression to the mean was driving these results, we performed an analysis that included baseline and change levels of social support indicators. RESULTS: At baseline, the frequency of leaving one's home was associated with a decrease in carotenoid levels. Leaving one's home more frequently predicted an increase in carotenoid levels and attending fewer activities predicted a decrease in carotenoid levels. IMPLICATIONS: In older, community-resident disabled women, baseline levels of social support did not consistently predict diet quality. However, change in social support predicted both positive and negative change in diet quality and thus provides supportive evidence that social activity and family interaction may play meaningful roles in the maintenance of diet quality among functionally compromised older women. Further research is necessary to more fully understand the impact of multiple forms of social supports on the diet quality of older adults.

Concordance between personality disorder assessment methods.

BACKGROUND: Studies have criticized the low level of agreement between the various methods of personality disorder (PD) assessment. This is an important issue for research and clinical purposes. METHOD: Seven hundred and forty-two participants in the Hopkins Epidemiology of Personality Disorders Study (HEPS) were assessed on two occasions using the Personality Disorder Schedule (PDS) and the International Personality Disorder Examination (IPDE). The concordance between the two diagnostic methods for all DSM-IV PDs was assessed using standard methods and also two item response analytic approaches designed to take account of measurement error: a latent trait-based approach and a generalized estimating equations (GEE)-based approach, with post-hoc adjustment. RESULTS: Raw criteria counts, using the intraclass correlation coefficient (ICC), κ and odds ratio (OR), showed poor concordance. The more refined statistical methods showed a moderate to moderately high level of concordance between the methods for most PDs studied. Overall, the PDS produced lower prevalences of traits but higher precision of measurement than the IPDE. Specific criteria within each PD showed varying endorsement thresholds and precision for ascertaining the disorder. CONCLUSIONS: Concordance in the raw measurement of the individual PD criteria between the two clinical methods is lacking. However, based on two statistical methods that adjust for differential endorsement thresholds and measurement error in the assessments, we deduce that the PD constructs themselves can be measured with a moderate degree of confidence regardless of the clinical approach used. This may suggest that the individual criteria for each PD are, in and of themselves, less specific for diagnosis, but as a group the criteria for each PD usefully identify specific PD constructs.

Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty.

OBJECTIVE: This project was designed to follow-up prior evidence that demonstrated a significant association between vitamin B12 transport and metabolism and the frailty syndrome in community-dwelling older women. The cross-sectional relationship between genetic variants within six candidate genes along this pathway with serum methylmalonic acid (MMA) levels and frailty was evaluated in this same population of older women. METHODS: Baseline measures were collected prior to folate fortification from 326 women in the Women's Health and Aging Studies I and II. Odds ratios and statistical tests were estimated for single SNP and haplotype via linear regression models for serum MMA, a marker for available vitamin B12, and in logistic regression models for frailty. RESULTS: Fifty-six SNPs from CBS, MTHFR, MTR, MTRR, TCN1 and TCN2 genes were genotyped. Several SNPs in MTHFR, MTR and MTRR demonstrated a modest association to elevated MMA, while SNPs in TCN2 showed significant association to the frailty syndrome. TCN2 polymorphisms, particularly one SNP reported to be in perfect LD with functional variant Pro259Arg, were significantly associated with increased odds of frailty, after adjustment for age, presence of cardiovascular disease and elevated MMA (OR = 2.25, p-value = 0.009). CONCLUSIONS: Using MMA as a marker for vitamin B12, these results suggest that TCN2 gene variants may lead to decreased vitamin B12 availability, leading to reduced energy metabolism, ultimately contributing to frailty pathology. Further studies to determine the biological role of functional TCN2 polymorphisms in frailty are needed.

Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (NC) mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed. METHODS: We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (FA) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE). RESULTS: Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable. CONCLUSIONS: Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression.

Allostatic load and frailty in the women's health and aging studies.

BACKGROUND: Frailty involves decrements in many physiologic systems, is prevalent in older ages, and is characterized by increased vulnerability to disability and mortality. It is yet unclear how this geriatric syndrome relates to a preclinical cumulative marker of multisystem dysregulation. The purpose of this study was to evaluate whether allostatic load (AL) was associated with the geriatric syndrome of frailty in older community-dwelling women. METHODS: We examined the cross-sectional relationship between AL and a validated measure of frailty in the baseline examination of two complementary population-based cohort studies, the Women's Health and Aging studies (WHAS) I and II. This sample of 728 women had an age range of 70-79. We used ordinal logistic regression to estimate the relationship between AL and frailty controlling for covariates. RESULTS: About 10% of women were frail and 46% were prefrail. AL ranged from 0 to 8 with 91% of participants scoring between 0 and 4. Regression models showed that a unit increase in the AL score was associated with increasing levels of frailty (OR = 1.16, 95% CI = 1.04-1.28) controlling for race, age, education, smoking status, and comorbidities. CONCLUSION: This study suggests that frailty is associated with AL. The observed relationship provides some support for the hypothesis that accumulation of physiological dysregulation may be related to the loss of reserve characterized by frailty.

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.

Markers of B-vitamin deficiency and frailty in older women.

OBJECTIVE: To evaluate the association between markers of vitamins B12, B6 and folate deficiency and the geriatric syndrome of frailty. DESIGN: Cross-sectional study of baseline measures from the combined Women's Health and Aging Studies. SETTING: Baltimore, Maryland. PARTICIPANTS: Seven hundred three community-dwelling women, aged 70-79. MEASUREMENTS: Frailty was defined by five-component screening criteria that include weight, grip strength, endurance, physical activity and walking speed measurements and modeled as binary and 3-level polytomous outcomes. Independent variables serum vitamin B6, vitamin B12, methylmalonic acid, total homocysteine, cystathionine and folate were modeled continuously and as abnormal versus normal. RESULTS: Serum biomarker levels varied significantly by race. All analyses were race-stratified and results are reported only for Caucasian women due to small African American sample size. In polytomous logistic regression models of 3-level frailty, Caucasian women with increasing MMA, defined either continuously or using a predefined threshold, had 40-60% greater odds of being prefrail (p-values < 0.07) and 1.66-2.33 times greater odds of being frail (p-values < 0.02) compared to nonfrails after adjustment for age, education, low serum carotenoids, alcohol intake, cardiovascular disease and renal impairment. Both binary and polytomous frailty models evaluating vitamin B12 as the main exposure estimated odds ratios that were similar in trend yet slightly less significant than the MMA results. CONCLUSIONS: These results suggest that vitamin B12 deficiency may contribute to the frailty syndrome in community-dwelling older women. Future studies are needed to explore these relationships longitudinally.

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p

Epidemiology of multiple childhood traumatic events: child abuse, parental psychopathology, and other family-level stressors.

BACKGROUND: Multiple family-level childhood stressors are common and are correlated. It is unknown if clusters of commonly co-occurring stressors are identifiable. The study was designed to explore family-level stressor clustering in the general population, to estimate the prevalence of exposure classes, and to examine the correlation of sociodemographic characteristics with class prevalence. METHOD: Data were collected from an epidemiological sample and analyzed using latent class regression. RESULTS: A six-class solution was identified. Classes were characterized by low risk (prevalence=23%), universal high risk (7 %), family conflict (11 %), household substance problems (22 %), non-nuclear family structure (24 %), parent's mental illness (13 %). CONCLUSIONS: Class prevalence varied with race and welfare status, not gender. Interventions for childhood stressors are person-focused; the analytic approach may uniquely inform resource allocation.

Widespread musculoskeletal pain and the progression of disability in older disabled women.

BACKGROUND: Widespread musculoskeletal pain is a poorly understood but common problem in older adults. Little is known about the progression of disability related to this condition. OBJECTIVE: To determine whether widespread musculoskeletal pain increases the risk for worsening disability in older women with disabilities. DESIGN: Prospective cohort study. SETTING: The Women's Health and Aging Study. PARTICIPANTS: 1002 community-dwelling women 65 years of age or older with disability. MEASUREMENTS: Widespread musculoskeletal pain was defined as pain in the upper and lower extremities and axial pain with moderate or severe pain in at least one of the three regions. Worsening disability was defined as progression from no or mild difficulty to severe difficulty or inability to perform activities of daily living (ADLs), walk one-quarter mile, or lift 10 lbs. RESULTS: At baseline, 24% of participants had widespread pain and 25% had no pain or only mild pain in a single site. Women with widespread pain were 2.5 to 3.5 times more likely to have severe difficulty with ADLs, walking, or lifting at baseline compared with women who had no or mild pain. In women without severe difficulty initially, widespread pain nearly doubled the risk for progression to severe difficulty in each of the tasks, after adjustment for age, body mass index, comorbid illness, and other confounders. CONCLUSION: Widespread musculoskeletal pain is frequent among community-dwelling older women with disability and appears to predict the progression of disability. Efforts to better understand the cause of this pain and its treatment might reduce the overall burden of disability.

Association of IGF-I levels with muscle strength and mobility in older women.

The functional consequences of the age-associated decline in IGF-I are unknown. We hypothesized that low IGF-I levels in older women would be associated with poor muscle strength and mobility. We assessed this question in a population representative of the full spectrum of health in the community, obtaining serum IGF-I levels from women aged 70-79 yr, enrolled in the Women's Health and Aging Study I or II. Cross-sectional analyses were performed using 617 women with IGF-I levels drawn within 90 d of measurement of outcomes. After adjustment for age, there was an association between IGF-I and knee extensor strength (P = 0.004), but not anthropometry or other strength measures. We found a positive relationship between IGF-I levels and walking speed for IGF-I levels below 50 microg/liter (P < 0.001), but no relationship above this threshold. A decline in IGF-I level was associated with self-reported difficulty in mobility tasks. All findings were attenuated after multivariate adjustment. In summary, in a study population including frail and healthy older women, low IGF-I levels were associated with poor knee extensor muscle strength, slow walking speed, and self-reported difficulty with mobility tasks. These findings suggest a role for IGF-I in disability as well as a potential target population for interventions to raise IGF-I levels.

Self-reported preclinical disability identifies older women with early declines in performance and early disease.

There appears to be a preclinical stage of physical disability which precedes onset of task difficulty (disability) in those who develop disability progressively as a result of chronic disease. Such a stage provides a basis for identifying older adults at risk of becoming disabled. This cross-sectional study evaluated whether a preclinical stage of physical function identified by self-report is associated with decrements in objective physical performance measures or increases in disease; that is, whether these measures, in those with preclinical disability, are intermediate between individuals who report no difficulty and no preclinical changes and those who report difficulty. The Women's Health and Aging Study II, an observational study of 436 women 70-80 years of age who were among the two-thirds least disabled living in the community. Participants were sampled from the HCFA Medicare eligibility lists and were determined eligible if they reported no difficulty, or difficulty in only one of four domains of physical function: mobility, upper extremity, IADL and ADL tasks. At the first follow-up (18 months after baseline), participants completed questionnaires on physical functioning for tasks in each of these domains, with possible answer options for each task: they had (1) difficulty (disabled); (2) no difficulty and no modification of task performance (High Function); or (3) no difficulty but reported modification and/or change in frequency of task performance (a self-report measure of preclinical disability predictive of incident difficulty). At the same visit, standardized, objective measures of function and disease were obtained, including measured walk; chair stands; strength: hip flexion, knee extension, ankle dorsiflexion, and grip; balance: function reach, single leg stand, tandem stand; joint exam: hip pain on passive motion and knee pain or tenderness; spirometry; ankle:arm blood pressure ratio; visual function: acuity, contrast sensitivity, stereopsis; and graded treadmill exercise test. Data were analyzed from the first follow-up examination. Physical performance decreased, and disease frequency increased, in association with decreasing self-reported mobility function (in walking one-half mile and climbing 10 steps), across three self-report categories: High Function, Preclinical Disability (Task Modification but No Difficulty) and Disability (Difficulty). These findings pertained for measures of walking speed, balance, strength, and knee and hip osteoarthritis. Self-reported level of function predicted differences in ranges as well as means for walking speed, balance and strength. These findings indicate a physiologic basis for self-reported function, including preclinical disability, specifically that different levels of disease severity, impairments and physical performance are concurrently associated with different categories of self-reported function. They also suggest new avenues for screening and intervention to prevent disability.