The influence of anxiety on the progression of disability

OBJECTIVES: To determine the influence of anxiety on the progression of disability and examine possible mediators of the relationship. DESIGN: Community-based observational study. SETTING: Women's Health and Aging Study I, a prospective observational study with assessments every 6 months for 3 years. PARTICIPANTS: One thousand two functionally limited women aged 65 and older. MEASUREMENTS: Anxiety symptoms were assessed using four questions from the Hopkins Symptom Checklist (nervous or shaky, avoidance of certain things, tense or keyed up, fearful). Participants who reported experiencing two or more of these symptoms at baseline were considered anxious. Anxiety as a predictor of the onset of four types of disability was examined using Cox proportional hazards models. Three models were tested: an unadjusted model, a model adjusted for confounding variables (age, race, vision, number of diseases, physical performance, depressive symptoms), and a mediational model (benzodiazepine and psychotropic medication use, physical activity, emotional support). RESULTS: Nineteen percent of women reported two or more symptoms of anxiety at baseline. Unadjusted models indicate that anxiety was associated with a greater risk of worsening disability: activity of daily living (ADL) disability (relative risk (RR)=1.40, 95% confidence interval (CI)=1.10-1.79), mobility disability (RR=1.41, 95% CI=1.06-1.86), lifting disability (RR=1.54, 95% CI=1.20-1.97), and light housework disability (RR=1.77, 95% CI=1.32-2.37). After adjusting for confounding variables, anxiety continued to predict the development of two types of disability: ADL disability (RR=1.41, 95% CI=1.08-1.84) and light housework disability (RR=1.56, 95% CI=1.14-2.14). Finally, benzodiazepine and psychotropic medication use, physical activity, and emotional support were not significant mediators of the effect of anxiety on the development of a disability. CONCLUSION: Anxiety is a significant risk factor for the progression of disability in older women. Studies are needed to determine whether treatment of anxiety delays or prevents disabilit

Inflammatory markers and incident mobility limitation in the elderly

OBJECTIVES: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons. DESIGN: Prospective cohort study: the Health, Aging and Body Composition Study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline. MEASUREMENTS: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFα), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months. RESULTS: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI) = 1.10-1.28) for IL-6, 1.20 (95% CI = 1.12-1.29) for TNFα and 1.40 (95% CI = 1.18-1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n = 499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR = 1.23 (95% CI = 1.04-1.46) and RR = 1.28 (95% CI = 1.04-1.57), respectively) were also associated with incident mobility limitation. CONCLUSION: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness

Inflammatory Markers and Onset of Cardiovascular Events: Results from the Health ABC Study

Background - Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons. Methods and Results - The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-\uce\ub1 (TNF-\uce\ub1) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-\uce\ub1 showed significant associations with CHD (per TNF-\uce\ub1 SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-\uce\ub1 SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile. Conclusions - Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons

Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults.

Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults. The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol. ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05). Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults

Association of a modified physiologic index with mortality and incident disability: the Health, Aging, and Body Composition study

Background.Indexes constructed from components may identify individuals who age well across systems. We studied the associations of a Modified Physiologic Index (systolic blood pressure, forced vital capacity, Digit Symbol Substitution Test score, serum cystatin-C, serum fasting glucose) with mortality and incident disability.Methods.Data are from the Health, Aging, and Body Composition study on 2,737 persons (51.2% women, 40.3% black) aged 70-79 years at baseline and followed on average 9.3 (2.9) years. Components were graded 0 (healthiest), 1 (middle), or 2 (unhealthiest) by tertile or clinical cutpoints and summed to calculate a continuous index score (range 0-10). We used multivariate Cox proportional hazards regression to calculate risk of death or disability and determined accuracy predicting death using the area under the curve.Results.Mortality was 19% greater per index unit (p <. 05). Those with highest index scores (scores 7-10) had 3.53-fold greater mortality than those with lowest scores (scores 0-2). The unadjusted index (c-statistic = 0.656, 95% CI 0.636-0.677, p <. 0001) predicted death better than age (c-statistic = 0.591, 95% CI 0.568-0.613, p <. 0001; for comparison, p <. 0001). The index attenuated the age association with mortality by 33%. A model including age and the index did not predict death better than the index alone (c-statistic = 0.671). Prediction was improved with the addition of other markers of health (c-statistic = 0.710, 95% CI 0.689-0.730). The index was associated with incident disability (adjusted hazard ratio per index unit = 1.04, 95% CI 1.01-1.07).Conclusions.A simple index of available physiologic measurements was associated with mortality and incident disability and may prove useful for identifying persons who age well across systems. © The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Depressive symptoms and change in abdominal obesity in older persons

CONTEXT: Depression has been hypothesized to result in abdominal obesity through the accumulation of visceral fat. No large study has tested this hypothesis longitudinally. OBJECTIVE: To examine whether depressive symptoms predict an increase in abdominal obesity in a large population-based sample of well-functioning older persons. DESIGN: The Health, Aging, and Body Composition Study, an ongoing prospective cohort study, with 5 years of follow-up. SETTING: Community-dwelling older persons residing in the areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: 2088 well-functioning white and black persons aged 70–79 years. MAIN OUTCOME MEASURES: Baseline depression was defined as a Center for Epidemiological Studies Depression (CES-D) score of ≥ 16. At baseline and after 5 years, overall obesity measures included body mass index and percent body fat (measured by dual energy x-ray absorptiometry). Abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat (measured by computed tomography). RESULTS: After adjustment for sociodemographics, lifestyle, diseases and overall obesity, baseline depression was associated with a 5-year increase in sagittal diameter (β=.054, p=.01) and visceral fat (β=.080, p=.001). CONCLUSIONS: This study shows that depressive symptoms result in an increase in abdominal obesity, independent of overall obesity, suggesting that there may be specific pathophysiological mechanisms which link depression with visceral fat accumulation. These results might also help explain why depression increases risk of diabetes and cardiovascular disease

Angiotensin converting enzyme insertion/deletion genotype, exercise and physical decline: evidence of a gene-environment interaction

Context: Physical performance in response to exercise appears to be influenced by the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genotype in young adults, but whether this relationship could help explain variation in older individuals' response to exercise has not been well studied. Objective: To determine whether the ACE genotype interacts with significant physical activity to affect the incidence of mobility limitation in well-functioning older adults. Design, Setting, and Participants: The Health Aging and Body Composition (Health ABC) Cohort Study, conducted in the metropolitan areas of Memphis, Tenn, and Pittsburgh, Pa. A total of 3075 well-functioning community-dwelling adults aged 70 through 79 years were enrolled from 1997 to 1998 and had a mean of 4.1 years of follow-up. Main Outcome Measure: Incident mobility limitation defined as the report of difficulty walking a quarter of a mile (0.4 km) or walking up 10 steps on 2 consecutive semiannual interviews (n=1204). Results: Physically active participants (those reporting expending ≥1000 kcal/wk in exercise, walking, and stair climbing) were less likely to develop mobility limitation regardless of genotype. However, activity level interacted significantly with the ACE genotype (P=.002). In the inactive group, the ACE genotype was not associated with limitation (P=.46). In the active group, those with the II genotype were more likely to develop mobility limitation after adjusting for potential confounders compared with those with ID/DD genotypes (adjusted rate ratio, 1.45, 95% confidence interval, 1.08-1.94). The gene association was especially strong among participants reporting weightlifting. Exploration of possible physiological correlates revealed that among active participants, those with the II genotype had higher percentage of body fat (P=.02) and more intermuscular thigh fat (P=.02) but had similar quadriceps strength as those with ID/DD. Conclusions: Among older individuals who exercised, those with the ACE DD or ID genotypes were less likely to develop mobility limitation than those with the II genotype. Regardless of genotype, individuals who exercised were less likely to develop mobility limitation than those who did not exercise. ©2005 American Medical Association. All rights reserved

Vascular Disease and Future Risk of Depressive Symptomatology in Older Adults: Findings from Health, Aging and Body Composition

Background: The vascular depression hypothesis suggests that age-related vascular diseases and risk factors contribute to late-life depression. Although neuroimaging studies provide evidence for an association between depression and severity of vascular lesions in the brain, studies of depression and indicators of vascular risk have been less consistent. Methods: We examined 1796 elders ages 70-79 from the Health, Aging and Body Composition study without depression at baseline and examined the association between prevalent vascular disease and related conditions at baseline and 2-year incidence of elevated depressive symptoms, defined as a score > 8 on the 10-item Center for Epidemiologic Studies Depression (CES-D) scale. Results: After adjustment for demographic data and physical and cognitive functioning, several vascular conditions remained associated with increased risk of depressive symptomatology including metabolic syndrome and its components (low high-density lipoprotein cholesterol and high fasting glucose), coronary heart disease, a positive Rose questionnaire for angina, and high hemoglobin a1c. Cumulative vascular risk based upon a composite of 10 vascular diseases and risk factors was independently associated with incident elevated depression at 2-year follow-up after controlling for demographic data, physical and cognitive functioning, and selected comorbid medical conditions. Conclusions: These results provide support for the vascular depression hypothesis in demonstrating an association between vascular conditions and risk factors and subsequent risk of depressive symptomatology. Older adults with vascular conditions and risk factors require close monitoring of depressive symptoms. © 2008 Society of Biological Psychiatry