Scant data exist on normal bolus dwell time assessed during Flexible Endoscopic Evaluation of Swallowing (FEES). The purpose of this study was to examine bolus dwell time in healthy older adults. Since it has been previously reported that some healthy older adults aspirate, we also sought to determine if bolus dwell time varied as function of aspiration status.
Seventy-six healthy volunteers from the 7th, 8th, and 9th decades of life participated. Dwell times were analyzed via FEES as a function of pharyngeal location, liquid type, delivery method, purée type, viscosity, age, and gender.
Longer dwell times were evidenced with the eldest participants, straw delivery, and the smallest volume. Adults in the 9th decade were 4.8 (p = 0.01) and 3.8 (p = 0.02) times more likely to have longer dwell times at the vallecula and 7.1 (p = 0.002) and 3.8 (p = 0.02) at the pyriform sinus than those in the 7th and 8th decades, respectively. Longer dwell times at the vallecula and pyriform sinuses were 2 and 2.38 times (p < 0.0001) more likely for straw than cup delivery, respectively. Five ml boluses were 1.5 times (p < 0.05) more likely to result in longer dwell times than larger volumes. Bolus dwell times did not significantly differ as a function of aspiration status.
Advanced age, straw delivery, and small volumes yielded longer dwell times. These variables should be considered before diagnosing an abnormal bolus dwell time in elder patients.
pharyngeal response; bolus dwell times; swallow; older adults; endoscopic; FEES
Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.
Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.
Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.
Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.
Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.
We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2–9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).
Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52–0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61–3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78–4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20–2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67–3.67]) (p = .55), as compared with smaller changes for both.
Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin–outcome associations reported previously.
Adiponectin; C-reactive protein; Interleukin 6; Aging; Mortality
This study examines the relationship between race and mobility over 5 years in initially well-functioning older adults and evaluates how a broad set of socioeconomic status indicators affect this relationship.
Data were from 2,969 black and white participants aged 70–79 from the Health, Aging, and Body Composition study. Mobility parameters included self-reported capacity to walk a quarter mile and climb 10 steps and usual gait speed. Incident mobility limitation was defined as reported difficulty walking a quarter mile or climbing 10 steps at two consecutive semiannual assessments. Gait speed decline was defined as a 4% reduction in speed per year.
At baseline, even though all participants were free of mobility limitation, blacks had slower walking speed than their white counterparts, which was not explained by poverty, education, reading level, or income adequacy. After 5 years, accounting for age, site, and baseline mobility, blacks were more likely to develop mobility limitation than whites. Adjusting for prevalent conditions at baseline eliminated this difference in women; controlling for education eliminated this difference in men. No differences in gait speed decline were identified.
Higher rates of mobility loss observed in older blacks relative to older whites appear to be a function of both poorer initial mobility status and existing health conditions particularly for women. Education may also play a role especially for men.
Race disparities—Functional limitations—SES—Disability
To examine the association between 25-hydroxyvitamin D (25[OH]D) and physical function in adults of advanced age.
Cross-sectional and longitudinal analysis of physical function over 3 years of follow-up in the Cardiovascular Health Study All Stars.
Forsyth County, NC; Sacramento County, CA; Washington County, MD; and Allegheny County, PA.
Community-dwelling adults aged 77–100 years (n=988).
Serum 25(OH)D, short physical performance battery (SPPB) and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADL) disability were assessed at baseline and every 6 months over 3 years of follow-up.
30.8% of participants had deficient 25(OH)D (<20 ng/mL). SPPB scores were lower among those with deficient 25(OH)D compared to those with sufficient 25(OH)D (≥30 ng/mL) after adjusting for sociodemographic characteristics, season, health behaviors and chronic conditions (mean±SE: 6.53±0.24 vs. 7.15±0.25, p <0.01). Grip strength adjusted for body size was also lower among those with deficient versus sufficient 25(OH)D (mean±SE: 24.7±0.6 vs. 26.0±0.6 kg, p <0.05). Participants with deficient 25(OH)D were more likely to have prevalent mobility and ADL disability at baseline (OR (95% CI): 1.44 (0.96–2.14) and 1.51 (1.01–2.25), respectively) compared to those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at increased risk of incident mobility disability over 3 years of follow-up (HR (95% CI): 1.56 (1.06–2.30)).
Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability among community-dwelling adults of advanced age. Moreover, vitamin D deficiency predicted incident mobility disability.
vitamin D; physical performance; muscle strength; mobility disability; ADL disability
One of the major problems in dietary assessment is inaccuracy in reporting diet.
To examine the association between self-reported energy intake by food frequency questionnaire (FFQ) and energy expenditure (EE), measured by doubly labeled water (DLW) among the elderly.
EE was assessed in 298 high-functioning, community-dwelling older adults over 2 weeks using DLW. Dietary intake was assessed using a Block Food Frequency Questionnaire (FFQ). The ratio between reported energy intake (EI) and total energy expenditure (TEE) was calculated. Misreporting was defined as: participants with an EI/TEE ratio of <0.77 were categorized as low energy reporters (LER) while participants with an EI/TEE ratio >1.28 were categorized as high energy reporters (HER). Participants with an EI/TEE ratio of 0.77–1.28 were categorized as “true” energy reporters (TER). One year percent weight change prior to EE visit was used as another validation indicator. Participants who were low energy reporters but lost >2% of their body weight were categorized as undereaters.
296 participants had both FFQ and DLW measurements. 43% of participants were low energy reporters among them, almost 30% lost weight and, therefore, were categorized as undereaters. The undereaters consumed significantly less calories. No difference in the frequency of low energy reporting was detected between gender or race groups. Underreporters had significantly higher body weight than “true” or high reporters. Undereaters tended to have higher BMI than the underreporters.
Undereating is prevalent in the elderly and may be falsely perceived as underreporting. It should be further addressed and characterized in future studies.
Doubly labeled water; missreporting; dietary inatke; true energy reporters; undereating
Previous cross-sectional studies demonstrate positive associations of fat-free mass and negative associations of centrally distributed fat deposits with respiratory function in older adults. Few studies have evaluated whether greater losses of muscle and increases in fat are associated with more rapid decline in respiratory function in aging.
Nine hundred and fifty-seven men and 1,024 women aged, respectively, 73.6 ± 2.8 years and 73.2 ± 2.8 years at baseline were followed for 5 years. Body weight, waist circumference, bone mineral density, fat-free mass, fat mass and fat mass percentage as measured by DXA, abdominal subcutaneous and visceral adipose tissue, thigh muscle area, thigh intermuscular fat by CT and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were evaluated at baseline and after 5-years follow-up.
Cross-sectional analyses showed that height and thigh muscle area were positively and visceral adipose tissue negatively related to FEV1 and FVC. Increase in fat mass over five years was associated with concurrent FEV1 and FVC decline. In analyses stratified by weight-change categories, men and women who gained weight (vs stable/lost weight) had more rapid declines in FEV1 and FVC.
In this well-functioning cohort, less muscle and greater abdominal fat were each associated with poorer lung spirometry cross-sectionally, whereas increase in fat mass over 5 years was associated with concurrent FEV1 and FVC decline. Weight gain and accompanying fat deposition may accelerate age-related declines in respiratory function.
Aging; Lung function; Body composition
Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.
We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA.
African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.
The impact of abnormal spirometric findings on risk for incident heart failure among older adults without clinically apparent lung disease is not well elucidated.
We evaluated the association of baseline lung function with incident heart failure, defined as first hospitalization for heart failure, in 2125 participants of the community-based Health, Aging, and Body Composition Study (age, 73.6±2.9 years; 50.5% men; 62.3% white; 37.7% black) without prevalent lung disease or heart failure. Abnormal lung function was defined either as forced vital capacity (FVC) or forced expiratory volume in 1st second (FEV1) to FVC ratio below lower limit of normal. Percent predicted FVC and FEV1 were also assessed as continuous variables.
During follow-up (median, 9.4years), heart failure developed in 68 of 350 (19.4%) participants with abnormal baseline lung function, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74-3.07; P<.001). This increased risk persisted after adjusting for previously identified heart failure risk factors in the Health ABC Study, body mass index, incident coronary heart disease, and inflammatory markers (HR, 1.83; 95% CI, 1.33-2.50; P<.001). Percent predicted (%) FVC and FEV1 had a linear association with heart failure risk (HR, 1.21; 95%CI, 1.11-1.32 and 1.18; 95%CI, 1.10-1.26, per 10% lower %FVC and %FEV1, respectively; both P<.001 in fully adjusted models). Findings were consistent in sex and race subgroups, and for heart failure with preserved or reduced ejection fraction.
Abnormal spirometric findings in older adults without clinical lung disease are associated with increased heart failure risk.
Elderly; Epidemiology; Heart Failure; Pulmonary Function Test
Recently, subclinical aspiration has been identified in approximately 30% of community-dwelling older adults. Given that the tongue is a key component of the safe swallow, we hypothesized healthy older adults who aspirate will generate less tongue strength than adults who do not aspirate. Furthermore, as muscle weakness may reflect a global effect of aging, we further investigated whether tongue strength is correlated with handgrip strength.
We assessed 78 healthy community-dwelling older adults (M = 77.3 years, SD = 7.26) for aspiration status (37% aspirators) via flexible endoscopic evaluation of swallowing. Maximal isometric anterior and posterior tongue strength, anterior and posterior swallowing tongue strength, and maximum handgrip strength were measured.
Isometric tongue strength was significantly lower in aspirators versus nonaspirators (p = .03) at both the anterior (463 vs 548 mmHg, respectively) and posterior lingual locations (285 vs 370 mmHg, respectively). Likewise, swallowing tongue strength was significantly lower in aspirators versus nonaspirators at both the anterior (270 vs 317 mmHg, respectively) and posterior lingual locations (220 vs 267 mmHg, respectively). There was no difference between aspirators and nonaspirators’ handgrip strength (p > .05), although handgrip strength was correlated with posterior tongue strength (r = .34, p = .005).
Lower anterior and posterior isometric and swallowing tongue strength were dependent on aspiration status. Lower lingual strength in healthy adults may predispose them to aspiration. The correlation between tongue and handgrip strength is consistent with the hypothesis that impaired oropharyngeal strength reflects global age-related declines in muscle strength.
Swallowing; Tongue; Handgrip; Aspiration; Healthy
Vitamin D deficiency is common among older adults and is associated with poor physical performance; however, studies examining longitudinal changes in 25-hydroxyvitamin D (25[OH]D) and physical performance are lacking. We examined the association between 25(OH)D and physical performance over 12 months in older adults participating in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multicenter physical activity intervention trial.
Plasma 25(OH)D and physical performance, assessed by the short physical performance battery (SPPB) and 400-m walk test, were measured at baseline, 6-month, and 12-month follow-up in community-dwelling adults aged 70–89 years at risk for disability (n = 368). Mixed models were used to examine the association between 25(OH)D and physical performance adjusting for demographics, intervention group, season, body mass index, and physical activity.
One half of the participants were vitamin D deficient (25[OH]D < 20 ng/mL) at baseline. In cross-sectional analyses, vitamin D deficiency was associated with lower SPPB scores and slower 400-m walk speeds (mean difference [SE]: 0.35 [0.16], p = .03 and 0.04 [0.02] m/s, p = .01, respectively). Although baseline 25(OH)D status was not significantly associated with change in physical performance over 12 months, individuals who were vitamin D deficient at baseline but no longer deficient at follow-up had significant improvements in SPPB scores (mean difference [SE]: 0.55 [0.22], p = .01) compared with those whose 25(OH)D status remained the same.
Increases in 25(OH)D to greater than or equal to 20 ng/mL were associated with clinically significant improvements in physical performance among older adults.
Vitamin D; Physical performance; Aging
The recently developed and internally validated Health ABC HF model uses nine routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.
Methods and Results
Observed 5-year incidence of heart failure, defined as first hospitalization for new onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5%) participants developed heart failure over 5 years vs. 364 (6.8%) predicted by the Health ABC HF model (predicted to observed ratio, 0.90). Observed vs. predicted 5-year heart failure probabilities were 3.2% vs. 2.8%, 9.0% vs. 7.0%, 15.9% vs. 13.7%, and 24.6% vs. 30.8% for the <5%, 5–10%, 10–20%, and >20% 5-year risk categories, respectively. The Hosmer-Lemeshow χ2 was 14.72 (d.f.=10; P=0.14) and the C index was 0.74 (95% CI, 0.72–0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however risk was underestimated in white men, especially in the 5–10% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.
The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to target heart failure prevention efforts.
Heart failure; epidemiology; elderly
Depression has been hypothesized to result in abdominal obesity through the accumulation of visceral fat. No large study has tested this hypothesis longitudinally.
To examine whether depressive symptoms predict an increase in abdominal obesity in a large population-based sample of well-functioning older persons.
The Health, Aging, and Body Composition Study, an ongoing prospective cohort study, with 5 years of follow-up.
Community-dwelling older persons residing in the areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee.
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).
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).
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.
Background and aims
Cross-sectional studies suggest that Obstructive Lung Disease (OLD) and smoking affect lean mass and mobility. We aimed to investigate whether OLD and smoking accelerate aging-related decline in lean mass and physical functioning.
260 persons with OLD (FEV1 63±18 %predicted), 157 smoking controls (FEV1 95±16 %predicted), 866 formerly smoking controls (FEV1 100±16 %predicted) and 891 never-smoking controls (FEV1 104±17 %predicted) participating in the Health, Aging and Body Composition (ABC) Study were studied. At baseline, the mean age was 74±3 y and participants reported no functional limitations. Baseline and seven-year longitudinal data were investigated of body composition (by Dual-energy X-ray absorptiometry), muscle strength (by hand and leg dynamometry) and Short Physical Performance Battery (SPPB).
Compared to never-smoking controls, OLD persons and smoking controls had a significantly lower weight, fat mass, lean mass and bone mineral content (BMC) at baseline (p<0.05). While the loss of weight, fat mass, lean mass and strength was comparable between OLD persons and never-smoking controls, the SPPB declined 0.12 points/yr faster in OLD men (p=0.01) and BMC 4 g/yr faster in OLD women (p=0.02). In smoking controls, only lean mass declined 0.1 kg/yr faster in women (p=0.03) and BMC 8 g/yr faster in men (p=0.02) compared to never-smoking controls.
Initially well-functioning older adults with mild-to-moderate OLD and smokers without OLD have a comparable compromised baseline profile of body composition and physical functioning, while seven-year longitudinal trajectories are to a large extent comparable to those observed in never-smokers without OLD. This suggests a common insult earlier in life related to smoking. 3
Obstructive Lung Disease; Body Composition; Aging
Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids.
We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a non-invasive measure of coronary artery disease burden.
Participants in the Multi-Ethnic Study of Atherosclerosis underwent CT assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men and 43% black), ages 47–86 years, from Forsyth County, NC during 2002–2005, using cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index using the standard scores of non-subcutaneous fat depots.
A total of 219 participants (55%) were found to have calcified coronary plaque. After adjusting for demographics, lifestyle factors and height, calcified coronary plaque was associated with a one standard deviation increment in the non-subcutaneous fat index (OR = 1.41; 95% CI: 1.08, 1.84), pericardial fat (OR = 1.38; 95% CI: 1.04, 1.84), abdominal visceral fat (OR = 1.35; 95% CI: 1.03, 1.76), but not with fat content in the liver, intermuscular fat, or abdominal subcutaneous fat. The relation between non-subcutaneous fat index and calcified coronary plaque remained after further adjustment for abdominal subcutaneous fat (OR = 1.40; 95% CI: 1.00, 1.94). The relation did not differ by gender and ethnicity.
The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis.
Although several cross-sectional studies have linked obesity and depression, less is known about their longitudinal association and about the relative influence of obesity subtypes. We prospectively examined whether (abdominal) obesity increased the risk of onset of depression in a population-based sample of older persons.
Participants were 2540 non-depressed well-functioning white and black persons, aged 70–79 years, enrolled in the Health ABC Study, an ongoing prospective community-based cohort study. Overall obesity was assessed by body mass index and percent body fat (measured by dual energy x-ray absorptiometry), whereas abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat (measured by computer tomography). Onset of significant depressive symptoms was defined as a Center for Epidemiological Studies Depression 10-item score ≥ 10 at any annual follow-up over 5 years and/or new antidepressant medication use. Persistent depression was defined as depression at two consecutive follow-up visits.
Over 5 years, significant depressive symptoms emerged in 23.7% of initially non-depressed persons. In men, both overall (BMI: HR per SD increase=1.20, 95%CI=1.03–1.40) and abdominal obesity (visceral fat: HR per SD increase=1.19, 95%CI=1.07–1.33) predicted onset of depressive symptoms after adjustment for sociodemographics. When BMI and visceral fat were adjusted for each other, only visceral fat was significantly associated with depression onset (HR=1.18, 95%CI=1.04–1.34). Stronger associations were found for persistent depressive symptoms. No associations were found in women.
This study shows that obesity, in particular visceral fat, increases the risk of onset of significant depressive symptoms in men. These results suggest that specific mechanisms might relate visceral fat to the onset of depression.
(abdominal) obesity; visceral fat; depression; older persons; longitudinal
Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m2) and women (n = 40, BMI = 33.3 ± 4.9 kg/m2) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (−1,160 vs. −647 cm3, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (−104 vs. −298 cm3, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: −43 vs. −88 cm3, P = 0.005; women: −34 vs. −59 cm3, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
A growing body of evidence has consistently shown a correlation between obesity and chronic sub-clinical inflammation. Several studies have suggested that measures of body fat distribution, rather than overall adiposity, may be more closely associated with inflammation level.
To investigate the relationship between levels of inflammatory markers and specific measures of abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat of older white and black adults.
Data of 2,651 black and white men and women aged 70-79 participating in the Health, Aging and Body Composition (Health ABC) study were used. Levels of the inflammatory markers, IL-6, CRP, and TNF-α were obtained from blood samples. The areas of abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on CT images. Linear regression analysis was used to evaluate the cross-sectional relationship between each body composition measure and serum levels of inflammatory markers in the four race/gender groups.
Abdominal visceral adiposity was most consistently associated with significantly higher IL-6 and CRP levels in all race/gender groups (p<0.05). Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammation level with increasing thigh subcutaneous fat in white and black women.
Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker level across all four subgroups examined.
To evaluate the association between inflammation and heart failure (HF) risk in older adults.
Inflammation is associated with HF risk factors and also directly affects myocardial function.
The association of baseline serum concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2610 older persons without prevalent HF enrolled in the Health ABC Study (age, 73.6±2.9 years; 48.3% men; 59.6% white).
During follow-up (median, 9.4 years), 311 participants (11.9%) developed HF. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, TNF-α, and CRP concentrations was associated with 29% (95% CI, 13 to 47%; P<.001), 46% (95% CI, 17 to 84%; P=.001), and 9% (95% CI, -1 to 24%; P=.087) increase in HF risk, respectively. In models including all three markers, IL-6 and TNF- α, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; P=.001) and fit (decreased Bayes information criterion by 17.8; P<.001).
Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.
Heart Failure; Elderly; Inflammation
To determine the effects of a 12-month physical activity intervention on inflammatory biomarkers in elderly men and women.
424 elderly (aged 70–89 years), nondisabled, community-dwelling men and women at risk for physical disability were enrolled in a multicenter, single-blind, randomized controlled-trial. Participants were randomized to participate in either a 12-month moderate-intensity physical activity (PA) intervention or a successful aging (SA) health education intervention. Biomarkers of inflammation (IL-6sR, IL-1sRII, sTNFRI, sTNFRII, IL-8, IL-15, adiponectin, IL-1ra, IL-2sRα, and TNF-α) were measured at baseline, 6 and 12 months.
A baseline blood sample was successfully collected from 368 participants. After adjustment for gender, clinic site, diabetes status, and baseline outcome measure, IL-8 was the only inflammatory biomarker affected by the PA intervention (p=0.03). The adjusted mean IL-8 at month 12 was 9.9% (0.87 pg/mL) lower in the PA compared to the SA group. Secondary interaction analyses between baseline biomarker status and treatment showed one significant interaction (p=0.02) such that the PA intervention reduced IL-15 concentrations in participants with a baseline IL-15 above the median value of 1.67 pg/mL. However, these associations were no longer significant after consideration for multiple comparisons.
Overall, this study does not provide definitive evidence for an effect of regular exercise for altering systemic concentrations of the measured inflammatory biomarkers in older adults.
exercise; aging; inflammation; cytokines; soluble receptors
Cross-sectional studies show that adiponectin is higher in older than in younger adults but long-term change in adiponectin, its determinants, and its relationship to functional decline or survival in the elderly population have not been evaluated.
We investigated predictors of longitudinal change in adiponectin, and the association of this adipokine or its antecedent change with physical deterioration and all-cause mortality in 988 participants in a population-based study who completed examinations in 1996–1997 and 2005–2006, had serial adiponectin measurements and underwent follow-up through June 2009.
Adiponectin level rose significantly during follow-up, but the increase was smaller in blacks, was associated with declining weight or fasting glucose and, in men, lower albumin, and was affected by medications. Adiponectin was independently associated with greater physical decline, but the relationship for adiponectin change was driven by concomitant weight decrease. Both adiponectin and its change independently predicted mortality, even after adjustment for weight change. The association for adiponectin and mortality was observed in whites but not in blacks and only for levels in the upper range (hazard ratio = 1.85, 95% confidence interval = 1.36–2.52 per SD ≥ 20 mg/L), whereas that for adiponectin change was linear throughout in both racial groups (hazard ratio = 1.30, 95% confidence interval = 1.10–1.52 per SD).
Adiponectin levels increase over time in long-lived adults and are associated with greater physical disability and mortality. Such increases may occur in response to age-related homeostatic dysregulation. Additional investigation is required to define the underlying mechanisms and whether this represents a marker or causal factor for mortality in this age group.
Adiponectin; Aging; Mortality; Physical Function
We examined whether a systemic marker of oxidative stress, F2-isoprostanes (F2-IP), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition study, F2-IP and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole body DXA and regional adiposity by abdominal and thigh CT scans at baseline and 5-year follow-up. ANOVA models were estimated to examine associations between F2-IP tertiles and baseline adiposity and changes in body composition. Median F2-IP was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, p<0.001). F2-IP was associated with higher levels of adiponectin, leptin, and TNF-α. Men in the highest F2-IP tertile had significantly higher total percent body fat than those in the lowest tertile. Positive associations were found between F2-IP and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow up, women in the highest versus lowest F2-IP tertile exhibited significant loss of weight (lowest tertile: −1.1 kg, highest tertile: −2.7 kg, p<0.05). In conclusion, F2-isoprostanes were associated with measures of total and regional adiposity in women and with total body fat in men; associations for women were partially explained by adipocytokines. F2-isoprostanes predicted loss of total adiposity over time among women.
Abdominal obesity; Adipokines; Adipose Tissue; Oxidative Stress; Weight Change
Strength, physical performance, adiposity and lean mass may be independent risk factors for disability in older adults. The aim of this study was to empirically identify groupings of these interrelated measures and test how such groupings may relate to disability risk.
Prospective Health, Aging and Body Composition Study (Health ABC)
Two US clinical centers
1,263 women and 1,221 men
Weight, strength (knee extension, grip); walking speed; chair stands; dual x-ray absorptiometry (fat and lean mass for total body, arm, and leg; percent fat); and thigh computed tomography scans (muscle area, muscle density). Analyses were stratified by sex. Factor analysis reduced these variables into a smaller number of components, and proportional hazards models assessed risk of major disability for the components identified.
In both sexes, factor analysis reduced the 14 individual variables into three components that explained 76–77% of the data variance: Factor 1, an adiposity component, with strong loading by fat mass, weight and muscle density; Factor 2, a strength/lean body size component with strong loading by lean mass, weight and strength; Factor 3, a physical performance component with positive loading by walking speed and chair stands performance. Factor 1 (adiposity) and Factor 3 (performance), but not Factor 2 (strength/lean body size), were associated with disability over 6.1 (± 2.6 SD) years.
Adiposity and physical performance constructs, but not the strength/lean body size construct, were associated with disability risk, suggesting that adiposity and performance should be considered as risk factors for disability.
lean mass; muscle; strength; disability; sarcopenia
An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible they will provide more definite evidence of causality. However, even when clinical trials are feasible, we can learn a great deal about the disease process, assessment techniques, subject selection criteria, and the impact of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of both unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons.
longitudinal studies; observational studies; clinical trials
As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap.
The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years.
LIFE's primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness.
Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.
Disability; Physical activity; Exercise; Geriatrics; Physical function