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Eleanor M Simonsick

Publications and source records attributed to Eleanor M Simonsick.

At least 19 recordsLinked to original sources
PubMed2026

Sex-specific biological aging clocks across organs and omics.

Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the importance of sex-stratified training for constructing sex-specific healthy normative references and then reveal marked divergence between female and male clocks. Key genetic parameters and Mendelian randomization results indicate that organ-specific aging liability and its relationships to cardiometabolic, endocrine and mental traits are configured differently in females and males. Proteomic analyses identify distinct, organ-resolved synaptic, immune, vascular and metabolic networks that differentially track female and male biological aging. In longitudinal survival analyses, sex-specific clocks predict whole-body systemic diseases and all-cause mortality in a sex-dependent and organ-dependent manner. Further analyses reveal sex-dependent associations between the brain aging clock and cognitive decline trajectory during a preclinical AD clinical trial. Sex-stratified clocks may offer distinct value by defining biological age against sex-appropriate normative references and revealing sex-dependent genetic, molecular and clinical signatures that pooled models may obscure. Meanwhile, sex-pooled and sex-interaction approaches remain valuable, as human aging and disease also share fundamental biological similarities between females and males. Together, these findings reveal sex-specific biological aging signatures in aging, AD and systemic health, highlighting the need for explicitly sex-stratified modeling approaches.

Journal Article↗
PubMed2007

Hypercortisolemic depression is associated with the metabolic syndrome in late-life.

INTRODUCTION: Depression has been hypothesized to be associated with metabolic abnormalities which increase the risk of cardiovascular disease (CVD) and diabetes. Such a link could be due to increased HPA-axis activity. This study investigates the cross-sectional relationship between depression, urinary cortisol and metabolic syndrome in an older population. METHODS: Data are from 867 participants of the InChianti Study, aged 65 years. Depressive symptoms were assessed using the CES-D scale; cortisol levels were determined in 24-h urine samples. Metabolic syndrome was defined as three or more of the following: abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. RESULTS: Clinically relevant depressed mood (CES-D20) was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After adjustment for sociodemographics and health indicators, depression score (per SD increase: OR=1.20, 95% CI=1.02-1.41) and urinary cortisol level (per SD increase: OR=1.23, 95% CI=1.01-1.51) were significantly associated with presence of metabolic syndrome. There was, however, a significant interaction (p=0.003) between depressed mood and urinary cortisol in the probability of having metabolic syndrome. The odds of metabolic syndrome in persons with both depressed mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02-3.34) compared to persons with neither condition. DISCUSSION: This study suggests a synergistic relationship between depression, cortisol and metabolic syndrome. Hypercortisolemic depression may constitute a specific risk group for the metabolic syndrome.

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PubMed2006

Cystatin C and measures of physical function in elderly adults: the Health, Aging, and Body Composition (HABC) Study.

Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function.

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PubMed2006

Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability.

CONTEXT: Aerobic fitness, an important predictor of cardiovascular disease and mortality, is difficult to assess by maximal exercise testing in older adults. Extended walking tests have been examined as outcome predictors in medically ill populations but not in community-dwelling older adults. OBJECTIVE: To determine whether an extended walking test predicts poor outcomes in older adults. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study enrolling 3075 community-dwelling adults aged 70 to 79 years living in Pittsburgh, Pa, or Memphis, Tenn. Of those participating in the Health, Aging, and Body Composition Study, 1584 (52%) were women and 1281 (42%) were black. Participants enrolled from March 1997 to April 1998. Ability to complete the long-distance corridor walk and total performance time was assessed at the baseline examination. MAIN OUTCOME MEASURES: Total mortality, incident cardiovascular disease, incident mobility limitation, and mobility disability were ascertained after a mean (SD) of 4.9 (0.9) years. RESULTS: Among patients eligible to exercise, 351 died, 308 had episodes of incident cardiovascular disease, 1116 had occurrences of mobility limitation, and 509 had occurrences of mobility disability. Inability to complete walking 400 m tended to be associated with a higher risk of mortality and incident cardiovascular disease and, after accounting for potential confounders, was associated with incident mobility limitation (212.6 vs 79.1 events/1000 person-years; adjusted hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.58-2.18; P<.001) and mobility disability (85.2 vs 28.8 events/1000 person-years; adjusted HR, 1.95; 95% CI, 1.56-2.44; P<.001). Of those who completed 400 m, each additional minute of performance time was associated with an adjusted HR of 1.29 (95% CI, 1.12-1.48) for mortality, 1.20 (95% CI, 1.01-1.42) for incident cardiovascular disease, 1.52 (95% CI, 1.41-1.63) for mobility limitation, and 1.52 (95% CI, 1.37-1.70) for disability after adjustment for demographics, health behaviors, clinical and subclinical disease, and cardiovascular disease risk factors. Findings were consistent in both men and women and blacks and whites. Among participants who completed the test and after adjusting for potential confounders, those in the poorest quartile of functional capacity (walk time >362 seconds) had a higher risk of death than those in the best quartile (walk time <290 seconds; adjusted HR, 3.23; 95% CI, 2.11-4.94; P<.001). CONCLUSIONS: Older adults in the community who reported no difficulty walking had a wide range of performance on this extended walking test. Ability to do the test and performance were important prognostic factors for total mortality, cardiovascular disease, mobility limitation, and mobility disability in persons in their eighth decade.

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PubMed2006

Myeloperoxidase polymorphism and cognitive decline in older adults in the Health, Aging, and Body Composition Study.

Myeloperoxidase, an antimicrobial enzyme, produces oxidative free radicals. Rarely found in normal brain tissue, myeloperoxidase has been detected in microglia associated with Alzheimer's disease plaques. The authors examined a G-463A polymorphism in the promoter region of the myeloperoxidase gene (MPO) to determine the relation of MPO variants to cognitive decline over 4 years in a cohort of adults, aged 70-79 years at baseline (1997-1998), recruited from Memphis, Tennessee, and Pittsburgh, Pennsylvania, into the Health, Aging, and Body Composition Study. In this sample, 8% of the participants had the AA, 36.9% the AG, and 55.2% the GG genotype of MPO. The frequency of AA and AG genotypes was higher in Blacks than Whites (11.2% vs. 5.9%, and 44.1% vs. 32.9%, respectively). Multivariate logistic regression analyses showed that, for participants with the MPO AA genotype, cognitive decline was 1.58 (95% confidence interval: 1.07, 2.35) times more likely than for participants with the AG genotype and 1.96 (95% confidence interval: 1.33, 2.88) times more likely than for those with the GG genotype. Interactions between MPO and race, sex, or the apolipoprotein gene were not significant. In this sample, MPO AA, associated with decreased production of myeloperoxidase, was found to be a risk factor for cognitive decline.

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PubMed2006

Transitions to mobility difficulty associated with lower extremity osteoarthritis in high functioning older women: longitudinal data from the Women's Health and Aging Study II.

OBJECTIVE: To assess the impact of lower extremity osteoarthritis (OA) on transitions to mobility difficulty, and to assess the influence of pain, excess weight, and quadriceps strength on these transitions. METHODS: We analyzed longitudinal data acquired from 199 participants in the Women's Health and Aging Study II (ages 70-79 years) who initially reported no lower extremity limitation (e.g., difficulty walking one-quarter mile) or difficulty in activities of daily living (ADL; e.g., transferring). Prevalent lower extremity OA was determined from validated algorithms encompassing multiple data sources. Markov transition models were created to analyze the first transition from no difficulty at baseline to lower extremity limitations, ADL difficulty, or both 18, 36, and 72 months later. RESULTS: Compared with women without OA (n = 140), a higher proportion of women with lower extremity OA (n = 59) initially reported pain on most days and more severe pain while walking (P < 0.05). Women with OA were also heavier, with a higher proportion being obese or overweight (P < 0.001). Lower extremity OA, higher body mass index, and lower knee extensor strength independently increased the risk of transition to combined lower extremity and ADL difficulty first over 72 months. CONCLUSION: Lower extremity OA increased the likelihood of developing difficulty in both lower extremity tasks and ADL over 72 months in a cohort of initially high functioning older women. Two modifiable factors, higher relative weight and lower knee extensor strength, substantially impacted these transitions, and therefore warrant increased attention in the management of lower extremity OA.

Activities of Daily Living↗
PubMed2006

Magnesium and muscle performance in older persons: the InCHIANTI study.

BACKGROUND: The role of magnesium in maintaining muscle integrity and function in older adults is largely unknown. OBJECTIVE: We aimed to investigate the relation between serum magnesium concentrations and muscle performance in older subjects. DESIGN: Data are from the baseline examination conducted between September 1998 and March 2000 of the InCHIANTI (aging in the Chianti area) study, a prospective epidemiologic survey of risk factors for late-life disability. From among 1453 randomly selected community residents completing a home interview, 1138 men (46%) and women (aged 66.7 +/- 15.2 y; x +/- SD) with complete data on muscle performance and serum magnesium who were not severely cognitively compromised and had no evidence of kidney disease or hypercalcemia were included in the analysis. Muscle performance was evaluated by grip strength, lower-leg muscle power, knee extension torque, and ankle extension isometric strength and was normalized for age and body mass index (BMI) within each sex. RESULTS: After adjustment for age, sex, BMI, laboratory variables, presence of chronic diseases, muscle area, muscle density, and physical activity level, serum magnesium concentrations were significantly associated with indexes of muscle performance, including grip strength (beta = 2.0 +/- 0.5, P = 0.0002), lower-leg muscle power (beta = 8.8 +/- 2.7, P = 0.001), knee extension torque (beta = 31.2 +/- 7.9, P < 0.0001), and ankle extension strength (beta = 3.8 +/- 0.5, P < 0.0001). CONCLUSIONS: The serum magnesium concentration is an independent correlate of muscle performance in older persons. Whether magnesium supplementation improves muscle function remains to be shown.

Activities of Daily Living↗
PubMed2006

Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort.

BACKGROUND: Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sarcopenia) and strength in association with mortality has not been examined. METHODS: Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70-79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-alpha considered as potential confounders. RESULTS: There were 286 deaths over an average of 4.9 (standard deviation = 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28-1.79) and 1.65 (95% confidence interval, 1.19-2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar. CONCLUSION: Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength.

Age Factors↗
PubMed2006

The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study.

BACKGROUND: The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. METHODS: Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. RESULTS: Both men and women lost strength, with men losing almost twice as much strength as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men, 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass ( approximately 1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was independently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (ss coefficients; men, -0.48 +/- 4.61, p =.92, women, -1.68 +/- 3.57, p =.64). CONCLUSIONS: Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength.

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PubMed2006

A little exercise.

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Activities of Daily Living↗
PubMed2006

Association of inflammatory markers with socioeconomic status.

BACKGROUND: This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. METHODS: Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-alpha were measured. RESULTS: Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-alpha compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. CONCLUSIONS: This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.

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PubMed2006

Correlates of use of antifracture therapy in older women with low bone mineral density.

BACKGROUND: Guidelines exist for treatment of low bone mineral density (BMD). Little is known about patient characteristics associated with use of treatment. OBJECTIVES: To determine patient-related correlates of medication use following screening dual x-ray absorptiometry (DXA) of older adults. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Pittsburgh, PA and Memphis, TN. PARTICIPANTS: Community-dwelling women between the ages 70 and 79 years enrolled in the Health, Aging, and Body Composition (Health ABC) Study. MEASUREMENTS: Risk factors for fracture and BMD of the hip were assessed at baseline. Patients and their community physicians were supplied the results of the DXA scan. Prescription and over-the-counter medication use was collected at annual exams for 2 years. RESULTS: Of 1,584 women enrolled in Health ABC, 378 had an indication for antifracture therapy and were not receiving such treatment at baseline. By the second annual follow-up examination, prescription antiresorptive medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or vitamin D supplementation. In adjusted models, the strongest predictor for use of any antifracture medicine was presence of osteoporosis [vs osteopenia, odds ratio (OR), 2.9 (1.7 to 4.7)], white race [OR, 2.6 (1.5 to 4.8)], and receipt of the flu shot [OR, 2.2 (1.3 to 3.8)]. Neither a history of falls nor prior fracture was associated with use of antifracture medications. CONCLUSION: Even when physicians of study participants were provided with DXA scan results, 70% of older high-functioning women with an indication for therapy did not start or remain on an antifracture therapy. Substantial room for improvement exists in fracture prevention following a diagnosis of low BMD-especially among women with a history of falls, prior fractures, and among black women.

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PubMed2006

Limited literacy and mortality in the elderly: the health, aging, and body composition study.

BACKGROUND: While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults. OBJECTIVE: To assess the association of limited literacy with mortality. DESIGN AND SETTING: Five-year prospective study from 1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA, who were from the Health, Aging, and Body Composition study. Subjects' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into limited (0 to 8th grade reading level) or adequate literacy (> or = 9th grade reading level). PARTICIPANTS: Two thousand five hundred and twelve black and white elders without baseline functional difficulties or dementia. MEASUREMENTS: Time to death. RESULTS: Participants' mean age was 75.6 years, 48% were male, 38% were black, and 24% had limited literacy; the median follow-up time was 4.2 years. Compared with those with adequate literacy, those with limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for demographics and socioeconomic status, co-morbid conditions, self-rated health status, health-related behaviors, health care access measures, and psychosocial status, limited literacy remained independently associated with mortality (HR 1.75; 95% CI, 1.27 to 2.41). CONCLUSIONS: Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly. Given the growth of the aging population and the prevalence of chronic diseases, the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation.

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PubMed2006

Estimating cardiorespiratory fitness in well-functioning older adults: treadmill validation of the long distance corridor walk.

OBJECTIVES: To determine criterion validity of the 400-m walk component of the Long Distance Corridor Walk (LDCW) and develop equations for estimating peak oxygen consumption (VO2) from 400-m time and factors intrinsic to test performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in older adults. DESIGN: Cross-sectional validation study. SETTING: Gerontology Research Center, National Institute on Aging, Baltimore, Maryland. PARTICIPANTS: Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the Baltimore Longitudinal Study of Aging between August 1999 and July 2000. MEASUREMENTS: The LDCW, consisting of a 2-minute walk followed immediately by a 400-m walk "done as quickly as possible" over a 20-m course was administered the day after maximal treadmill testing. HR and SBP were measured before testing and at the end of the 400-m walk. Weight, height, activity level, perceived effort, and stride length were also acquired. RESULTS: Peak VO2 ranged from 12.2 to 31.1 mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6 minutes 18 seconds. Correlation between 400-m time and peak VO2 was -0.79. The estimating equation from linear regression included 400-m time (partial coefficient of determination (R2)=0.625), long versus short stride (partial R2=0.090), ending SBP (partial R2=0.019), and a correction factor for fast 400-m time (<240 seconds; partial R2=0.020) and explained 75.5% of the variance in peak VO2 (correlation coefficient=0.87). CONCLUSION: A 400-m walk performed as part of the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low-cost, safe assessments of fitness in clinical and research settings can identify early evidence of physical decline and individuals who may benefit from therapeutic interventions.

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PubMed2006

Limited literacy in older people and disparities in health and healthcare access.

OBJECTIVES: To determine the relationship between health literacy, demographics, and access to health care. DESIGN: Cross-sectional study, Health, Aging and Body Composition data (1999/2000). SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred twelve black and white community-dwelling older people who were well functioning at baseline (without functional difficulties or dementia). MEASUREMENTS: Participants' health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into 0 to sixth-, seventh- to eighth-, and ninth-grade and higher reading levels (limited health literacy defined as <9th grade). Participants' demographics, socioeconomic status, comorbidities, and three indicators of healthcare access (whether they had a doctor/regular place of medical care, an influenza vaccination within the year, or insurance for medications) were also assessed. RESULTS: Participants' mean age was 75.6, 52% were female, 38% were black, and 24% had limited health literacy. After adjusting for sociodemographics, associations remained between limited health literacy and being male, being black, and having low income and education, diabetes mellitus, depressive symptoms, and fair/poor self-rated health (P<.02). After adjusting for sociodemographics, health status, and comorbidities, older people with a sixth-grade reading level or lower were twice as likely to have any of the three indicators of poor healthcare access (odds ratio=1.96, 95% confidence interval=1.34-2.88). CONCLUSION: Limited health literacy was prevalent and was associated with low socioeconomic status, comorbidities, and poor access to health care, suggesting that it may be an independent risk factor for health disparities in older people.

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PubMed2006

Dog ownership, walking behavior, and maintained mobility in late life.

OBJECTIVES: To examine dog walking among dog owners and the relationship between walking behavior of dog owners and non-dog owners and maintained gait speed over 3 years. DESIGN: Cross-sectional and longitudinal analyses of a prospective cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred thirty-three community-dwelling adults aged 71 to 82 at 36 months of the Health, Aging and Body Composition Study. MEASUREMENTS: Dog ownership, reported walking behavior, change in walking behavior, and usual and rapid gait speed over 3 years. RESULTS: Of 394 dog owners, only 36% walked their dogs at least three times per week. Cross-sectionally, dog walkers were more likely to achieve 150 minutes of walking per week and had faster usual and rapid walking speeds (1.20 vs 1.14 m/s and 1.62 vs 1.52 m/s, respectively; P < .01 for both) than non-dog owners who did not walk at least three times per week and similar speeds as non-dog owners who walked at least 150 minutes per week (P > .50). Three years later, subjects who had been dog walkers at baseline were approximately twice as likely as any other group to achieve recommended walking levels, independent of covariates. Dog walkers experienced similar declines in usual and rapid walking speed as non-dog owners who walked at least three times per week but maintained their initial mobility advantage. CONCLUSION: Although dog ownership appears to facilitate walking behavior, only a minority of older dog owners walk their dogs. The mobility advantage of dog ownership was seen only in dog walkers and was similar to that associated with any walking. Given suboptimal walking activity in older adults, examining the degree to which dog ownership promotes walking activity in persons who do little walking on their own appears worth pursuing.

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PubMed2006

Diabetes, inflammation, and functional decline in older adults: findings from the Health, Aging and Body Composition (ABC) study.

OBJECTIVE: Age, diabetes, and elevated inflammatory markers independently increase the risk of functional decline. We examined the effect of C-reactive protein (CRP) and interleukin-6 (IL-6) on the incident mobility limitation in older adults with and without diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from a cohort of 2,895 well-functioning adults aged 70-79 years, followed for development of persistent functional limitation over 3.5 years. Participants were assessed for the presence of diabetes according to fasting glucose and/or hypoglycemic medication use and were divided into three equal groups (tertiles) according to level of CRP or IL-6. Persistent functional limitation was defined as difficulty climbing 10 steps or walking one-quarter mile on two consecutive semiannual assessments. RESULTS: At baseline, 702 participants (24%) had diabetes. CRP values were (median +/- SD) 2.8 +/- 4.4 versus 3.7 +/- 5.4 for those with normal glucose and diabetes, respectively (P < 0.001). The unadjusted incidence of functional limitation associated with increased levels of CRP and IL-6 was greater among participants with diabetes. After adjusting for clinical and demographic covariates, persistent functional limitation for the highest tertile was greater compared with that for the lowest tertile of CRP or IL-6 for those with and without diabetes. CRP hazard ratios (HRs) were 1.7 (95% CI 1.2-2.3) versus 1.4 (1.1-1.6), respectively. IL-6 HRs were 1.8 (1.3-2.5) versus 1.6 (1.4-2.0), respectively. CONCLUSIONS: In initially high-functioning older adults, those with diabetes and higher inflammatory burden had an increased risk of functional decline. Interventions at early stages to reduce inflammation may preserve function in these individuals.

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