Faculty Bibliography

BACKGROUND: Due to a shortage of studies focusing on older adults, clinicians and policy makers frequently rely on clinical trials of the general population to provide supportive evidence for treating complex, older patients. OBJECTIVES: To examine the inclusion and analysis of complex, older adults in randomized controlled trials. REVIEW METHODS: A PubMed search identified phase III or IV randomized controlled trials published in 2007 in JAMA, NEJM, Lancet, Circulation, and BMJ. Therapeutic interventions that assessed major morbidity or mortality in adults were included. For each study, age eligibility, average age of study population, primary and secondary outcomes, exclusion criteria, and the frequency, characteristics, and methodology of age-specific subgroup analyses were reviewed. RESULTS: Of the 109 clinical trials reviewed in full, 22 (20.2%) excluded patients above a specified age. Almost half (45.6%) of the remaining trials excluded individuals using criteria that could disproportionately impact older adults. Only one in four trials (26.6%) examined outcomes that are considered highly relevant to older adults, such as health status or quality of life. Of the 42 (38.5%) trials that performed an age-specific subgroup analysis, fewer than half examined potential confounders of differential treatment effects by age, such as comorbidities or risk of primary outcome. Trials with age-specific subgroup analyses were more likely than those without to be multicenter trials (97.6% vs. 79.1%, p < 0.01) and funded by industry (83.3% vs. 62.7%, p < 0.05). Differential benefit by age was found in seven trials (16.7%). CONCLUSION: Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multimorbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age.

BACKGROUND: Geriatric conditions, collections of symptoms common in older adults and not necessarily associated with a specific disease, increase in prevalence with advancing age. These conditions are important contributors to the complex health status of older adults. Diabetes mellitus is known to co-occur with geriatric conditions in older adults and has been implicated in the pathogenesis of some conditions. OBJECTIVE: To investigate the prevalence and incidence of geriatric conditions in middle-aged and older-aged adults with diabetes. DESIGN: Secondary analysis of nationally-representative, longitudinal health interview survey data (Health and Retirement Study waves 2004 and 2006). PARTICIPANTS: Respondents 51 years and older in 2004 (n=18,908). MAIN MEASURES: Diabetes mellitus. Eight geriatric conditions: cognitive impairment, falls, incontinence, low body mass index, dizziness, vision impairment, hearing impairment, pain. KEY RESULTS: Adults with diabetes, compared to those without, had increased prevalence and increased incidence of geriatric conditions across the age spectrum (p< 0.01 for each age group from 51-54 years old to 75-79 years old). Differences between adults with and without diabetes were most marked in middle-age. Diabetes was associated with the two-year cumulative incidence of acquiring new geriatric conditions (odds ratio, 95% confidence interval: 1.8, 1.6-2.0). A diabetes-age interaction was discovered: as age increased, the association of diabetes with new geriatric conditions decreased. CONCLUSIONS: Middle-aged, as well as older-aged, adults with diabetes are at increased risk for the development of geriatric conditions, which contribute substantially to their morbidity and functional impairment. Our findings suggest that adults with diabetes should be monitored for the development of these conditions beginning at a younger age than previously thought.

BACKGROUND: Some patients with diabetes may have health status characteristics that could make diabetes self-management (DSM) difficult and lead to inadequate glycemic control, or limit the benefit of some diabetes management interventions. OBJECTIVE: To investigate how many older and middle-aged adults with diabetes have such health status characteristics. DESIGN: Secondary data analysis of a nationally representative health interview survey, the Health and Retirement Study, and its diabetes mail-out survey. SETTING/PARTICIPANTS: Americans aged 51 and older with diabetes (n = 3506 representing 13.6 million people); aged 56 and older in diabetes survey (n = 1132, representing 9.9 million). MEASUREMENTS: Number of adults with diabetes and (a) relatively good health; (b) health status that could make DSM difficult (eg, comorbidities, impaired instrumental activities of daily living; and (c) characteristics like advanced dementia and activities of daily living dependency that could limit benefit of some diabetes management. Health and Retirement Study measures included demographics. Diabetes Survey included self-measured HbA1c. RESULTS: Nearly 22% of adults > or =51 with diabetes (about 3 million people) have health characteristics that could make DSM difficult. Another 10% (1.4 million) may receive limited benefit from some diabetes management. Mail-out respondents with health characteristics that could make DSM difficult had significantly higher mean HbA1c compared with people with relatively good health (7.6% vs. 7.3%, P < 0.04.). CONCLUSIONS: Some middle-aged as well as older adults with diabetes have health status characteristics that might make DSM difficult or of limited benefit. Current diabetes quality measures, including measures of glycemic control, may not reflect what is possible or optimal for all patient groups.

Cardiovascular disease is the major cause of death as well as a leading cause of disability and impaired quality of life in older adults with diabetes. Therefore, preventing cardiovascular events in this population is an important goal of care. Available evidence supports the use of lipid-lowering agents and treatment of hypertension as effective measures to reduce cardiovascular risk in older adults with diabetes. Glucose control, smoking cessation, weight control, regular physical activity, and a prudent diet are also recommended, although data supporting the efficacy of these interventions are limited. While reducing cardiovascular morbidity and mortality remains a primary objective of preventive cardiology in older adults with diabetes, the impact of these interventions on functional well-being, cognition, and other geriatric syndromes requires further study.

BACKGROUND: Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear. METHODS: Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures. RESULTS: Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems. CONCLUSIONS: Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty.

OBJECTIVES: To determine whether hyperglycemia is related to prevalent frailty status in older women. DESIGN: Secondary data analysis of baseline data of a prospective cohort study. SETTING: Baltimore, Maryland. PARTICIPANTS: Five hundred forty-three women aged 70 to 79. METHODS: Research used baseline data from 543 participants in the Women's Health and Aging Studies I and II aged 70 to 79 who had all variables needed for analyses. The dependent variable was baseline frailty status (not frail, prefrail, frail), measured using an empirically derived model defining frailty according to weight loss, slow walking speed, weakness, exhaustion, and low activity (1-2 characteristics present=prefrail, > OR =3 =frail). Covariates included body mass index (BMI), interleukin-6 (IL-6), age, race, and several chronic diseases. Analyses included descriptive methods and multinomial logistic regression to adjust for key covariates. RESULTS: A hemoglobin A1c (HbA1c) level of 6.5% or greater in older women was significantly associated with higher likelihood of prefrail and frail status (normal HbA1c <6.0% was reference). The association between HbA1C levels of 6.0% to 6.5% and frailty status was not different from that of normal HbA1c, but HbA1c levels of 6.5% to 6.9% had nearly twice the likelihood of frailty (odds ratio (OR)=1.96, 95% confidence interval (CI)=1.47-2.59) as normal HbA1c. A HbA1c level of 9.0% or greater was also strongly associated (OR=2.57, 95% CI=1.99,3.32). Significant associations were also seen between baseline prefrail and frail status and low (18.5-20.0 kg/m2) and high (430.0 kg/m2) body mass index (BMI), interleukin-6, and all chronic diseases evaluated, but controlling for these covariates only minimally attenuated the independent association between HbA1c and frailty status. CONCLUSION: Hyperglycemia is associated with greater prevalence of prefrail and frail status; BMI, inflammation, and comorbidities do not explain the association. Longitudinal research and study of alternative pathways are needed.

OBJECTIVES: To operationalize and compare three models of frailty, each representing a distinct theoretical view of frailty: as deficiencies in function (Functional Domains model), as an index of health burden (Burden model), and as a biological syndrome (Biologic Syndrome model). DESIGN: Cross-sectional analysis. SETTING: 2004 wave of the Health and Retirement Study, a nationally representative, longitudinal health interview survey. PARTICIPANTS: Adults aged 65 and older (N=11,113) living in the community and in nursing homes in the United States. MEASUREMENTS: The outcome measure was the presence of frailty, as defined according to each frailty model. Covariates included chronic diseases and sociodemographic characteristics. RESULTS: Almost one-third (30.2%) of respondents were frail according to at least one model; 3.1% were frail according to all three models. The Functional Domains model showed the least overlap with the other models. In contrast, 76.1% of those classified as frail according to the Biologic Syndrome model and 72.1% of those according to the Burden model were also frail according to at least one other model. Older adults identified as frail according to the different models differed in sociodemographic and chronic disease characteristics. For example, the Biologic Syndrome model demonstrated substantial associations with older age (adjusted odds ratio (OR)=10.6, 95% confidence interval (CI)=6.1-18.5), female sex (OR=1.7, 95% CI=1.2-2.5), and African-American ethnicity (OR=2.1, % CI=1.0-4.4). CONCLUSION: Different models of frailty, based on different theoretical constructs, capture different groups of older adults. The different models may represent different frailty pathways or trajectories to adverse outcomes such as disability and death.

OBJECTIVES: To analyze the co-occurrence, in adults aged 65 and older, of five conditions that are highly prevalent, lead to substantial morbidity, and have evidence-based guidelines for management and well-developed measures of medical care quality. DESIGN: Secondary data analysis of the 2004 wave of the Health and Retirement Study (HRS). SETTING: Nationally representative health interview survey. PARTICIPANTS: Respondents in the 2004 wave of the HRS aged 65 and older. MEASUREMENTS: Self-reported presence of five index conditions (three chronic diseases (coronary artery disease, congestive heart failure, and diabetes mellitus) and two geriatric syndromes (urinary incontinence and injurious falls)) and demographic information (age, sex, race, living situation, net worth, and education). RESULTS: Eleven thousand one hundred thirteen adults, representing 37.1 million Americans aged 65 and older, were interviewed. Forty-five percent were aged 76 and older, 58% were female, 8% were African American, and 4% resided in a nursing home. Respondents with more conditions were older and more likely to be female, single, and residing in a nursing home (all P<.001). Fifty-six percent had at least one of the five index conditions, and 23% had two or more. Of respondents with one condition, 20% to 55% (depending on the index condition) had two or more additional conditions. CONCLUSION: Five common conditions (3 chronic diseases, 2 geriatric syndromes) often co-occur in older adults, suggesting that coordinated management of comorbid conditions, both diseases and geriatric syndromes, is important. Care guidelines and quality indicators, rather than considering one condition at a time, should be developed to address comprehensive and coordinated management of co-occurring diseases and geriatric syndromes.

OBJECTIVES: Although congestive heart failure (CHF) is a common condition, the extent of disability and caregiving needs for those with CHF are unclear. We sought to determine: (1) prevalence of physical disability and geriatric conditions, (2) whether CHF is independently associated with disability, (3) rates of nursing home admission, and (4) formal and informal in-home care received in the older CHF population. METHODS: We used cross-sectional data from the 2000 wave of the Health and Retirement Study. We compared outcomes among three categories of older adults: (1) no coronary heart disease (CHD), (2) CHD, without CHF, and (3) CHF. Compared to those without CHF, respondents reporting CHF were more likely to be disabled (P < 0.001) and to have geriatric conditions (P < 0.001). Respondents reporting CHF were more likely to have been admitted to a nursing home (P < 0.05). CHF respondents were more functionally impaired than respondents without CHF. RESULTS: The adjusted average weekly informal care hours for respondents reporting CHF was higher than for those reporting CHD but without CHF and those reporting no CHD (6.7 vs 4.1 vs 5.1, respectively; P < 0.05). Average weekly formal caregiving hours also differed among the three groups (1.3 CHF vs 0.9 CHD without CHF vs 0.7 no CHD; P > 0.05). CONCLUSIONS: CHF imposes a significant burden on patients, families, and the long-term care system. Older adults with CHF have higher rates of disability, geriatric conditions, and nursing home admission.