Objectives

To test the hypothesis that anemia (hemoglobin <12 g/dL) is associated with a faster rate of 9-year cognitive decline in a community-dwelling sample of women aged 70-80 years at baseline.

Design

A population-based, prospective cohort study

Setting

East Baltimore, Maryland

Participants

436 women sampled to be representative of the 2/3 least disabled women in, aged 70-80 years at baseline (1994-1996).

Measurements

9-year trajectories of cognitive decline, analyzed with linear random effects models, in the domains of immediate verbal recall, delayed verbal recall, psychomotor speed, and executive function.

Results

At baseline and after adjustment for demographic and disease covariates, women with anemia were slower to complete a test of executive function than women without anemia by - 0.43 SD (95% CI: −0.74, −0.13) on the Trail Making Test, Part B (TMTB). During follow-up, anemia was associated with a faster rate of decline in memory. Between baseline and year 3, women with anemia declined at a rate of 0.18 more SD/year (95% CI: −0.29, −0.06) than women without anemia on the Hopkins Verbal Learning Test (HVLT) and by .0.15 more SD/year (95% CI: −0.26. −0.04) on the Hopkins Verbal Learning Test-Delayed (HVLT-Delayed).

Conclusion

Anemia was associated with poorer baseline performance on a test of executive function and with faster rates of decline on tests of immediate and delayed verbal recall. If this relationship is causal, it is possible that treatment of anemia could prevent or postpone cognitive decline.

Frailty is associated with a pro-inflammatory state, which has been characterized by elevated levels of systemic inflammatory biomarkers, but has not been related to the number of co-existing chronic diseases associated with inflammation. We sought to determine the extent to which a higher number of inflammatory-related diseases is associated with frailty and to identify the most common disease patterns associated with being frail in older adults. We performed binomial regression analyses to assess whether a higher count of inflammatory-related diseases increases the probability of frailty using data from the Women's Health and Aging Studies I and II, companion cohorts composed of 70–79-year-old community-dwelling older women in Baltimore, Maryland (n=620). An increase of one inflammatory-related disease was associated log-linearly with frailty (Prevalence Ratio (PR)=2.32, 95% Confidence Interval (CI)=1.85–2.92). After adjusting for age, race, education, and smoking status, the probability of frailty remained significant (PR=1.97, 95%CI=1.52–2.55). In the frail population, chronic kidney disease (CKD) and depressive symptoms (Prevalence=22.9%, 95%CI=14.2–34.8%); CVD and depressive symptoms (21.7%, 95%CI=13.2–33.5%); CKD and anemia (18.7%, 95%CI=11.1–29.7%); cardiovascular disease (CVD), CKD, and pulmonary disease (10.7%, 95%CI=5.2–21.0%); CKD, anemia, and depressive symptoms (8.7%, 95%CI=3.9–18.2%); and CVD, anemia, pulmonary disease, and depressive symptoms (5.0%, 95%CI=1.6–14.4%) were among the most frequent disease combinations. Their prevalence percentages were significantly higher in the frail versus non-frail women. A higher inflammatory-related disease count, perhaps reflecting a greater pro-inflammatory burden, increases the likelihood of frailty. Shared mechanisms among specific disease combinations may further contribute to this risk.

Experience Corps® places teams of trained volunteers in elementary school classrooms to promote academic achievement in children, and serve as a health promotion intervention for older adults. Prior to randomization, individuals reported participation in several activities of varying cognitive, physical, and social demands. Maintaining an active lifestyle, particularly in intellectually demanding activities, was associated with physical, mental, and cognitive health in adulthood. Establishing how individuals allocated their time before randomization to this program provides insight to prevalent health behaviors for at-risk older adults, and can provide the basis for examining intervention-related changes in lifestyle as a result of volunteer participation

In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65495–503-specific CD8+ T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65495–503-specific CD8+ T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65495–503 tetramer-positive CD8+ T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p < 0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8+ T cells specific for the CMV immunodominant epitope pp65495–503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.

This study examined whether participation in a variety of lifestyle activities was comparable to frequent participation in cognitively challenging activities in mitigating impairments in cognitive abilities susceptible to aging in healthy, community-dwelling older women. Frequencies of participation in various lifestyle activities on the Lifestyle Activities Questionnaire (LAQ) were divided according to high (e.g., reading), moderate (e.g., discussing politics), and low (e.g., watching television) cognitive demand. We also considered the utility of participation in a variety of lifestyle activities regardless of cognitive challenge. Immediate and delayed verbal recall, psychomotor speed, and executive function were each measured at baseline and at five successive exams, spanning a 9.5-year interval. Greater variety of participation in activities, regardless of cognitive challenge, was associated with an 8 to 11% reduction in the risk of impairment in verbal memory and global cognitive outcomes. Participation in a variety of lifestyle activities was more predictive than frequency or level of cognitive challenge for significant reductions in risk of incident impairment on measures sensitive to cognitive aging and risk for dementia. Our findings offer new perspectives in promoting a diverse repertoire of activities to mitigate age-related cognitive declines.

Objective

Although fibroblast growth factor 23 (FGF23) has been implicated in the pathogenesis of cardiovascular disease, the relationship between FGF23 and cardiovascular disease has not been well characterized in the general population. The aim of the study was to determine whether serum FGF23 is independently associated with cardiovascular disease in older community-dwelling women.

Design and methods

A cross-sectional design was used to examine the relationship between serum FGF23 and cardiovascular disease. The subjects consisted of a population-based sample of 659 women, aged 70–79 years, who participated in the Women’s Health and Aging Studies in Baltimore, Maryland. Prevalent cardiovascular disease (coronary heart disease, stroke, congestive heart failure, peripheral artery disease) was assessed through diagnostic algorithms and physician adjudication.

Results

Of the 659 women, 185 (28.1%) had cardiovascular disease. Median (25th, 75th percentile) intact serum FGF23 was 34.6 (25.2, 46.2) pg/mL. The prevalence of cardiovascular disease in the lowest, middle, and highest tertile of serum FGF23 was 22.6%, 24.9%, and 36.7%, respectively (P = 0.002). Serum log FGF23 was associated with cardiovascular disease (Odds Ratio per 1 SD increase = 1.23, 95% Confidence Interval 1.17, 1.30; P <0.0001) in a multivariable logistic regression model, adjusting for age, race, smoking, education, body mass index, cognition, diabetes, hypertension, physical activity, total cholesterol, HDL cholesterol, and renal function.

Conclusion

Elevated serum FGF23 concentrations are independently associated with prevalent cardiovascular disease in older community-dwelling women. Further studies are needed to elucidate the potential biological mechanisms by which FGF23 may be involved in the pathogenesis of cardiovascular disease.

Background.

In the general population, frailty, a late stage of the aging process, predicts mortality. We investigated whether manifesting a previously defined frailty-related phenotype (FRP) before initiating highly active antiretroviral therapy (HAART) affects the likelihood of developing clinical AIDS or mortality after HAART initiation.

Methods.

Among 596 HIV-infected men in the Multicenter AIDS Cohort Study whose date of HAART initiation was known within ±6 months and who had an assessable FRP status within 3 years before HAART, survival analyses were performed to assess the effect of FRP manifestation on clinical AIDS or death after HAART.

Results.

In men free of AIDS before HAART, AIDS or death after HAART occurred in 13/36 (36%) men who exhibited the FRP before HAART but only in 69/436 (16%) men who did not (hazard ratio = 2.6; 95% confidence interval = 1.4–4.6; p < .01). After adjusting for age, ethnicity, education, nadir CD4+ T-cell count, peak HIV viral load, and hemoglobin in the 3 years before HAART, having the FRP at >25% of visits in the 3 years before HAART significantly predicted AIDS or death (adjusted hazard ratio = 3.8; 95% confidence interval = 1.9–7.9; p < .01). Results were unchanged when the analysis was restricted to the 335 AIDS-free men who were HAART responders, to the 124 men who had AIDS at HAART initiation, or to the subsets of men for whom indices of liver and kidney function could be taken into account.

Conclusion.

Having a persistent frailty-like phenotype before HAART initiation predicted a worse prognosis after HAART, independent of known risk factors.

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. Our aim was to characterize the relationship between serum carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking disability (inability to walk or walking speed <0.4 m/sec) over 30 months of followup in 394 moderately to severely disabled women, ≥65 years, living in the community in Baltimore, Maryland (the Women's Health and Aging Study I). During followup, 154 (26.4%) women developed severe walking disability, and 23 women died. Women in the highest quartile of serum CML had increased risk of developing of severe walking disability in a multivariate Cox proportional hazards model, adjusting for age and other potential confounders. Women with elevated serum CML are at an increased risk of developing severe walking disability. AGEs are a potentially modifiable risk factor. Further work is needed to establish a causal relationship between AGEs and walking disability.

Although educational attainment has been consistently related to cognition in adulthood, the mechanisms are still unclear. Early education, and other social learning experiences, may provide the skills, knowledge, and interest to pursue intellectual challenges across the life course. Therefore, cognition in adulthood might reflect continued engagement with cognitively complex environments. Using baseline data from the Baltimore Experience Corps Trial, multiple mediation models were applied to examine the combined and unique contributions of intellectual, social, physical, creative, and passive lifestyle activities on the relationship between education and cognition. Separate models were tested for each cognitive outcome (i.e., reading ability, processing speed, memory). With the exception of memory tasks, findings suggest that education-cognition relations are partially explained by frequent participation in intellectual activities. The association between education and cognition was not completely eliminated, however, suggesting that other factors may drive these associations.

Low socioeconomic status (SES) is associated with increased risk for adverse health outcomes; those with low SES are thought to experience more environmental disadvantage and exposure to chronic stress over the life course. The effects of chronic stress on health have been measured by cortisol levels and variations in their diurnal pattern. However, the patterns of association between SES and cortisol have been equivocal in older adults. This paper examined in 98 older adults participating in the Brain Health Substudy of the Baltimore Experience Corps Trial baseline patterns of diurnal variation in salivary cortisol associated with lower versus higher SES using total income and perceived SES relative to others. For each measure, participants stratified into lower vs. higher SES showed a more blunted rate of decline in diurnal salivary cortisol over the day in adjusted models (P values ≤ 0.05). There were no SES-related differences in awakening cortisol, cortisol awakening response, or area under the curve. These findings confirm prior evidence of a biologic pathway through which socioeconomic disadvantage is linked to biologic vulnerability, and through which the impact of volunteer service in Experience Corps may be measured.

Background and Aims

Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semi-quantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women’s Health and Aging Study (WHAS).

Methods

Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by “relative influence” in predicting low physical activity. We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality.

Results

Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive.

Conclusions

We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

Background.

To examine the impact of educational attainment on the incidence of preclinical mobility disability (PCD).

Methods.

The Women's Health and Aging II Study is a prospective observational cohort study of 436 initially high-functioning community-dwelling women aged 70–79 years at baseline in Baltimore, Maryland. We measured the association of highest attained education level with preclinical mobility disability (PCD) over an 11-year period. PCD is defined as self-reported modification in any of four tasks without reporting difficulty in those tasks. The tasks were walking ½ mile, climbing up steps, doing heavy housework, and getting in/out of bed or chair.

Results.

Participants with less than 9 years of education were more likely to acquire incident PCD (hazard ratio: 3.1, 95% confidence interval = 1.2–7.7) than their counterparts with more education after adjusting for income, marital status, number of diseases, and high self-efficacy.

Conclusions.

Lower education level is an independent predictor of incident preclinical mobility disability. This association has important implications for primary and secondary prevention and can be easily assessed in clinical encounters.

Background

Chronic disease is a risk factor for frailty. Previous studies typically consider individual diagnosed diseases, but disease builds over time, possibly in several organs simultaneously.

Objective

We hypothesize that disease burden is associated with frailty independent of diagnosed chronic disease and that physiologic measurements provide greater understanding of the etiology of frailty.

Design

Cross-sectional study.

Setting

Community.

Participants

Cardiovascular Health Study, 1992–93 examination (N=2437, mean (SD) age 74.8 (4.8) years, 43.4% male, 95.8% white).

Measurements

Disease burden and frailty were tabulated using 10-point scales (0=healthy, 10=unhealthy). Disease burden was the sum of measurements characterizing the vasculature, brain, kidneys, lungs, and glucose metabolism. Frailty was assessed with the frailty index reported by Fried. Multivariate linear models were used to determine the association of disease burden (predictor) to frailty (outcome).

Results

Unadjusted, 1 point higher disease burden was associated with a 0.28 point higher frailty score (p<0.0001). White matter grade, forced vital capacity, and cystatin-C were particularly strongly and significantly associated with frailty. Disease burden attenuated the association of frailty with age by 29%, and disease burden and age had similar associations with frailty. Disease burden attenuated the association of frailty with fibrinogen, Factor VIII, and CRP by 32%, 56%, and 83%. Frailty was associated with diagnosed depression, stroke, cognitive impairment, arthritis, and pulmonary disease but not coronary heart disease, diabetes, or kidney disease in the presence of a summary of disease burden. In the adjusted model disease burden remained significantly associated with frailty (β=0.11, p<0.0001).

Conclusion

Disease burden was independently and significantly associated with frailty. These results emphasize that typically unrecognized physiologic changes may importantly contribute to frailty.

Objective

To describe the relationship between lower extremity physical performance, self-reported mobility difficulty and self-reported use of compensatory strategies for mobility inside the home.

Design

Cross sectional, exploratory study.

Setting

Community-dwelling elders.

Participants

Disabled, cognitively-intact women ≥65 years old (n=1002), from the Women’s Health and Aging Study I.

Interventions

N/A

Main Outcome Measures

Compensatory strategy (CS) scale: No CS, Behavioral Modifications (BM) only, Durable Medical Equipment (DME) with or without use of behavioral modifications, and any use of Human Help (HH); and 3 dichotomous CS measures: Any CS (vs none); DME±HH (vs BM only, among users of any CS); Any HH (vs DME only, among users of any DME/HH).

Results

Self reported mobility difficulty and physical performance were significantly correlated with one another (r=−0.57, p<0.0001) and with the CS Scale (r=0.51, p<0.001 and r=−0.54, p<0.0001 respectively). Sequential logistic regressions showed self reported difficulty and physical performance were significant independent predictors of each category of CS. For the Any CS and DME±HH models, the Odds Ratio (OR) for self reported difficulty decreased by ~50% when physical performance was included in the model, compared to difficulty alone (18.0 to 8.6 and 7.3 to 3.8 respectively), but both physical performance and difficulty remained significant predictors (p<0.0001). The effects of covariates differed for the various CS categories, with some covariates having independent relationships to compensatory strategy, and others appearing to have moderating or mediating effects on the relationship of self reported difficulty or physical performance to CS.

Conclusions

Physical performance, self reported difficulty, health conditions, and contextual factors have complex effects on the way elders carry out mobility inside the home.

Background & Aims

Red cell distribution width (RDW), a measure of heterogeneity in the size of circulating erythrocytes, is associated with some chronic diseases and predicts mortality. Although oxidative damage and inflammation have been theorized to affect RDW, the relationships of antioxidants and inflammation with RDW have not been well characterized. The aims were to determine whether total serum carotenoids, α-tocopherol, selenium, protein carbonyls, and interleukin-6 (IL-6) are associated with RDW and predict RDW over time.

Methods

RDW was measured at baseline, 12 months, and 24 months follow-up in 786 moderately to severely disabled community-dwelling women, aged ≥65 years, in the Women’s Health and Aging Study I in Baltimore, Maryland.

Results

Selenium was significantly associated with RDW at baseline and predicted RDW over two years’ follow-up in separate multivariate mixed effects models that adjusted for other covariates. As expected, the addition of IL-6 to the models attenuated the association of serum selenium with RDW, as low antioxidant levels are known to upregulate IL-6. Total carotenoids were associated with RDW at baseline and one year follow-up. Protein carbonyls and α-tocopherol were not significantly associated with RDW.

Conclusion

Serum selenium is an independent predictor of RDW and may potentially mediate effects on RDW through IL-6.

Background.

Older women experience disability more commonly than their male peers. This disparity may be due, in part, to sex-based differences in the prevalence or the disabling effects of common medical conditions. The objectives of this analysis were to (a) quantify the extent to which excess disability in women is explained by higher prevalence of selected medical conditions and (b) evaluate whether the same conditions have differing effects on disability in men and women.

Methods.

We analyzed cross-sectional data from 5,888 community-dwelling older men and women. Disability was defined as difficulty with greater than or equal to one activity of daily living. Thirteen medical conditions were assessed by self-report, testing, or record review.

Results.

Controlling for age, race, education, and marital status, women were more likely to experience disability (odds ratio = 1.70, 95% confidence interval = 1.36–2.11). Higher prevalence of arthritis and obesity in women explained 30.2% and 12.9%, respectively, of the sex-based difference in disability rates, whereas male prevalent diseases like vascular conditions and emphysema narrowed the disability gap. Women with arthritis, hearing problems, coronary artery disease, congestive heart failure, stroke, and claudication were more likely to exhibit disability compared with men with the same conditions (p < .001).

Conclusions.

Efforts to lessen sex-based inequality in disability should focus on reducing the prevalence of arthritis and obesity. Future generations may see greater functional disparity if rates of vascular disease and emphysema rise among women. Several conditions were more often associated with disability in women, suggesting additional sex-based differences in the disablement process.

Introduction

The relationship between self-reported function and objective measures of physiological function among disabled older women was analyzed to determine the validity of self-reported function, and to identify the hierarchy of self-reported task difficulty most associated with loss of independence as a basis to inform treatment progress goals.

Methods

A randomly selected population of older women with moderate to high disability was selected from community-dwelling women 65–101 years old from the Women’s Health and Aging Study I baseline evaluation (N=987). Cross-sectional analyses evaluated the association of self-reported function with objective physiological impairment measures.

Results

The results indicated that: (a) disabled older women self-reported a broad range of physical function levels; (b) self-reported function correlated closely with objective measures of physiological impairments; (c) “preclinical disability,” as measured by self-reported modification of task performance in the absence of perceived difficulty, has validity even in a disabled population, and identifies a group intermediate between those who are high functioning in a task and those with difficulty, and (d) there is an apparent gradation in physiological impairment measures with reported loss of functional independence.

Conclusion

These findings suggest the validity of self-report functional disability measures and the potential to use these measures to identify already-disabled older adults at risk for further functional degradation and potential targets for intervention.

OBJECTIVES

To assess the relationship between rate of change in muscle strength and all-cause mortality.

DESIGN

A prospective observational study of the causes and course of physical disability.

SETTING

Twelve contiguous ZIP code areas in Baltimore, Maryland.

PARTICIPANTS

Three hundred and seven community-dwelling women aged 70–79 years at study baseline.

MEASUREMENTS

The outcome is all-cause mortality (1994–2009); predictors include up to seven repeated measurements of handgrip, knee extension, and hip flexion strength, with a median follow-up time of 9 years. Demographic factors, body mass index, smoking status, number of chronic diseases, depressive symptoms, physical activity, Interlukin-6, and albumin were assessed at baseline and included as confounders. The associations between declining muscle strength and mortality were assessed using a joint longitudinal and survival model..

RESULTS

Grip and hip strength declined an average of 1.10 and 1.31 kg per year between age 70 and 75and 0.50 and 0.39 kg/year thereafter, respectively; knee strength declined at a constant rate of 0.57 kg/year. Faster rates of decline in grip and hip strength, but not knee strength, independently predicted of mortality after accounting for their baseline levels and potential confounders (Hazard Ratio (HR)=1.33 (95% confidence interval (CI)=1.06–1.67), 1.14 (CI=0.91–1.41), and 2.62 (CI=1.43–4.78) for every 0.5 standard deviation increase in rate of decline in grip, knee, and hip strength, respectively.

CONCLUSION

Monitoring the rate of decline in grip and hip flexion strength in addition to the absolute levels may greatly improve the identification of women most at risk of dying.

The Experience Corps®, a community-based intergenerational program, was developed to promote the health of older adults, while simultaneously addressing unmet social and academic needs in public elementary schools. The model was designed to draw on, and potentially activate, the wisdom of older adults. This paper explores the nature of wisdom-related knowledge and how older adults may apply such knowledge when tutoring and mentoring young children, as well as the potential for the intergenerational transmission of wisdom from the older adult volunteers to the school children being mentored by them. Developing an understanding of these issues may provide a basis for the creation of more extensive wisdom-generating opportunities for both older and younger generations.

In immunocompetent persons, cytomegalovirus (CMV) is thought to persist primarily in monocytes and myeloid progenitor cells, establishing a chronic infection. In older adults, chronic CMV infection is typically diagnosed by a positive IgG serology. While many studies have shown CMV-specific T-cell expansion in CMV seropositive older individuals, significant heterogeneity has also been observed in this elderly population. In a study of 71 community-dwelling older adults, we assessed CMV viral DNA in peripheral monocytes by nested PCR and compared the relationships of detectable CMV DNA and IgG serology with serum levels of neopterin, a marker for monocyte/macrophage-mediated immune activation. The results showed that 52 (73.2%) participants were CMV seropositive, of whom 30 (57.5%) had detectable CMV DNA. CMV seropositive and seronegative participants did not differ in their neopterin levels, but individuals with detectable CMV DNA had higher neopterin than those without (10.6±4.4 vs 8.0±1.9nM, respectively, p<.0001) adjusting for demographic and clinical covariates and interferon (IFN)-γ levels. In addition, there was no association between IgG titers and neopterin. These findings suggest that detection of CMV viral DNA in monocytes may be an informative tool to evaluate chronic CMV infection and its potential role in monocyte/macrophage-mediated immune activation in the elderly.

Annual immunization with a trivalent inactivated vaccine (TIV) is considered efficacious for prevention of seasonal influenza in older adults. However, significant controversy exists in the current literature regarding the clinical effectiveness of TIV immunization in this highly heterogeneous population. Frailty is an important geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability to stressors. Using a validated set of frailty criteria, we conducted a prospective observational study to evaluate TIV-induced strain-specific hemagglutination inhibition (HI) antibody titers and post-vaccination rates of influenza-like illness (ILI) and infection in frail and nonfrail older adults. The results indicate that frailty was associated with significant impairment in TIV-induced strain-specific HI titers and increased rates of ILI and laboratory-confirmed influenza infection. These findings suggest that assessing frailty status in the elderly may identify those who are less likely to respond to TIV immunization and be at higher risk for seasonal influenza and its complications.

Cytomegalovirus (CMV), a prevalent pathogen, causes severe disease in immunocompromised humans. However, present understanding is limited regarding the long-term clinical effect of persistent CMV infection in immunocompetent adults. The authors conducted a prospective observational cohort study (1992–2002) of 635 community-dwelling women in Baltimore, Maryland, aged 70–79 years in the Women's Health and Aging Studies to examine the effect of CMV infection on the risk of frailty, a common geriatric syndrome, and mortality in older women. The effect of baseline serum CMV antibody (immunoglobulin G) concentration on the risk of 3-year incident frailty, defined by using a 5-component measure, and 5-year mortality was examined with Cox proportional hazards models. Compared with those who were CMV seronegative, women in the highest quartile of CMV antibody concentration had a greater incidence of frailty (hazard ratio = 3.46, 95% confidence interval: 1.45, 8.27) and mortality (hazard ratio = 3.81, 95% confidence interval: 1.64, 8.83). After adjustment for potential confounders, CMV antibody concentration in the highest quartile independently increased the risk of 5-year mortality (hazard ratio = 2.79, 95% confidence interval: 1.22, 6.40). Better understanding of the long-term clinical consequences of CMV infection in immunocompetent humans is needed to guide public health efforts for this widely prevalent infection.

Background

Developing interventions to prevent frailty in older adults is a priority as it increases the risk for disability, institutionalization, and death. Single chronic inflammatory diseases are known to increase the risk of frailty. Identification of comorbid inflammatory diseases that synergistically might heighten this risk would provide further insight into therapeutic approaches to prevent frailty. The study aims were to characterize whether there are specific inflammatory disease pairs that are associated with frailty and to determine whether the risk of frailty is affected by synergistic interactions between these inflammatory diseases.

Methods

Data were from the Women's Health and Aging Studies I and II and complementary cohorts of community-dwelling women aged 70–79 years from Baltimore, Maryland (n = 620). Multivariable logistic regression analyses were performed to evaluate the relationships between these diseases and frailty.

Results

Among the frail (11.3%), 15.2% had both depressive symptoms and anemia and 14.5% had pulmonary disease and anemia. The risk of frailty was synergistically increased in those with depressive symptoms and anemia (adjusted risk ratios = 11.93, 95% confidence interval [CI] 4.10–34.76) and those with pulmonary disease and anemia (risk ratios = 5.57, 95% CI 2.14–14.48), compared with those without either disease in each pair. The attributable proportions of frail cases due to interaction between the diseases of each pair were 0.56 (95% CI 0.07–1.05) and 0.61 (95% CI 0.18–1.05), respectively.

Conclusions

Synergistic interactions between specific inflammatory diseases may heighten the risk of frailty. These findings suggest that a common etiologic pathway may exist among co-occurring inflammatory diseases and that their improved comanagement may be an approach to reducing frailty.

Background

A decline in exercise capacity (EC) is a characteristic of frailty. We hypothesized that decline is the effect of decrements in several physiological systems. We assessed whether the relationship of three main physiological systems—cardiac, pulmonary, and musculoskeletal—to EC is independent or interactive and whether their effect on EC varies with respect to frailty status.

Methods

Observational study of 547 disabled women aged 65 years and older (Women’s Health and Aging Study I) including 131 frail who participated in a test of EC. EC (seated step test), cardiac function (chronotropic index), pulmonary function (forced vital capacity, FVC), musculoskeletal function (quadriceps strength, QS), and frailty status were measured and interactive effects were modeled using linear regression and differentiation.

Results

Each physiological system had a direct relationship with EC, which was lower in frail compared with nonfrail. The relationship between FVC and EC was positive and increased with increasing QS in nonfrail subjects. The effect of QS on EC was positive and increased with increasing FVC regardless of frailty. In subjects with low QS, frailty status was associated with lower EC and this effect became stronger with increasing FVC.

Discussion

Findings suggest but do not show that frailty status modifies the effects of physiological function in several systems on EC. Approaches to understanding emergent properties such as vulnerability to illness and death and clinical efforts to prevent and treat frailty should evaluate and possibly intervene on several physiological systems to be maximally effective.

Background

Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear.

Methods

Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed.

Results

Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11–1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12–1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07–1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07–1.18). Furthermore, the RDW–mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21–1.44).

Conclusions

RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.