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1.  Physical Activity and Years of Healthy Life in Older Adults: Results From the Cardiovascular Health Study 
Little is known about how many years of life and disability-free years seniors can gain through exercise. Using data from the Cardiovascular Health Study, the authors estimated the extra years of life and self-reported healthy life (over 11 years) and years without impairment in activities of daily living (over 6 years) associated with quintiles of physical activity (PA) in older adults from different age groups. They estimated PA from the Minnesota Leisure Time Activities Questionnaire. Multivariable linear regression adjusted for health-related covariates. The relative gains in survival and years of healthy life (YHL) generally were proportionate to the amount of PA, greater among those 75+, and higher in men. Compared with being sedentary, the most active men 75+ had 1.49 more YHL (95% CI: 0.79, 2.19), and the most active women 75+ had 1.06 more YHL (95% CI: 0.44, 1.68). Seniors over age 74 experience the largest relative gains in survival and healthy life from physical activity.
PMCID: PMC3978479  PMID: 20651417
aging; exercise; mortality; health status; activities of daily living
2.  Skeletal Muscle Mitochondrial Energetics Are Associated With Maximal Aerobic Capacity and Walking Speed in Older Adults 
Background.
Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults.
Methods.
Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by 31P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3).
Results.
In vitro St3 respiration was significantly correlated with in vivo ATPmax (r 2 = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r 2 = .33, p = .006). ATPmax (r 2 = .158, p = .03) and VO2 peak (r 2 = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r 2 = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed.
Conclusions.
Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age.
doi:10.1093/gerona/gls196
PMCID: PMC3593613  PMID: 23051977
Muscle; Mitochondria; Aging; Walking speed.
3.  Reproducibility of peroneal motor nerve conduction measurement in older adults 
Objective
While neuropathy is common in the elderly, nerve conduction (NC) reproducibility in older adults is not well-established. We sought to evaluate intraobserver reproducibility of peroneal motor NC measures in a diverse sample of older adults.
Methods
We measured peroneal motor NC amplitude and velocity in a subset of participants (mean age=82.9 ± 2.7, n=62, 50% female, 51.6% black, 35.5% DM) in the Health, Aging, and Body Composition Study. Using coefficients of variation (CVs), intraclass correlation coefficients (ICCs), and Bland Altman Plots, we compared two sets of measurements taken by the same examiner hours apart on the same day.
Results
Low CVs (2.15–4.24%) and moderate to high ICCs (0.75–0.99) were observed. No systematic variation was found across measures. Despite small numbers in some subgroups, we found no differences in reproducibility by diabetes, race, or study site.
Conclusion
NC measures have moderate to high intraobsever reproducibility in older adults and are not affected by diabetes, race, or gender.
Significance
These data provide evidence to support use of these measures in aging research.
doi:10.1016/j.clinph.2012.07.027
PMCID: PMC3562564  PMID: 23022036
Motor nerve conduction; aging; peripheral nerve function; reproducibility; diabetes
4.  Hypertension and Low HDL-Cholesterol were Associated with Reduced Kidney Function Across the Age Spectrum: A Collaborative Study 
Annals of epidemiology  2013;23(3):106-111.
Purpose
To determine if the associations among established risk factors and reduced kidney function vary by age.
Methods
We pooled cross-sectional data from 14,788 non-diabetics aged 40–100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.
Results
Hypertension and low HDL-cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% CI 0.1, 4.4), 5.1 (4.1, 6.1), and 6.9 (3.0, 10.4) mL/min/1.73 m2 lower eGFR in participants 40–59, 60–79, and 80+ years, respectively (p-value for interaction <0.001). The association of low HDL-cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (3.5, 6.3), 7.1 (CI 6.0, 8.3), 8.9 (CI 5.4, 11.9) mL/min/1.73 m2 (p-value for interaction <0.001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.
Conclusions
Hypertension, obesity, smoking, and low HDL-cholesterol are modestly associated with reduced kidney function in non-diabetics. The associations of hypertension and HDL-cholesterol with reduced kidney function appear stronger in older adults.
doi:10.1016/j.annepidem.2012.12.004
PMCID: PMC3570601  PMID: 23313266
Chronic kidney insufficiency; aged; hypertension; cholesterol; obesity; smoking
5.  Risk Factors for Hospitalization Among Older Persons Newly Diagnosed with Heart Failure: The Cardiovascular Health Study 
Objective
To identify risk factors for the occurrence of all-cause hospitalizations among older persons following heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors when evaluated in the context of other relevant clinical data.
Background
Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk of hospitalization following heart failure diagnosis. With the aging of the heart failure population, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common.
Methods
The study population included participants with incident heart failure from the Cardiovascular Health Study, a longitudinal study of community-living, older persons. Data were collected through annual examinations and medical record review. Anderson-Gill regression modeling was used to determine predictors of hospitalization after heart failure diagnosis.
Results
Of the 758 participants newly diagnosed with heart failure, the mean rate of hospitalization was 7.9 per 10 person-years (95% CI 7.4–8.4). Independent risk factors for occurrence of hospitalizations included depressed ejection fraction (HR 1.25, 95% CI 1.04–1.51), NYHA classes 3 or 4 (HR 1.32, 95% CI 1.11–1.57), diabetes mellitus (HR 1.36, 95% CI 1.13–1.64), chronic kidney disease (HR 1.32 95% CI 1.14–1.53), weak grip strength (HR 1.19, 95% CI 1.00–1.42), slow gait speed (HR 1.28 95% CI 1.06–1.55), and depression (HR 1.23, 95% CI 1.05–1.45).
Conclusions
Geriatric conditions are important, and potentially modifiable, risk factors for hospitalization in heart failure that should be routinely assessed at the time of heart failure diagnosis.
doi:10.1016/j.jacc.2012.11.027
PMCID: PMC3576871  PMID: 23391194
Heart Failure; Hospitalizations; Geriatric conditions
6.  European ancestry and resting metabolic rate in older African Americans 
Background/Objectives
Resting metabolic rate (RMR) contributes 60–80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through SNP analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans.
Subjects/Methods
RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7 ± 3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex.
Results
Mean EA was 23.8 ± 16% (range: 0.1% to 70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (p = 0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association.
Conclusions
European ancestry in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.
doi:10.1038/ejcn.2011.22
PMCID: PMC3915864  PMID: 21468093
Admixture; energy metabolism; body composition; genetic mapping
7.  Pulse wave velocity and cognitive decline in elders: The Health, Aging and Body Composition study 
Background and Purpose
Arterial stiffness is a measure of subclinical cardiovascular disease (CVD) and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults.
Methods
2,488 subjects with baseline measure of arterial stiffness (mean age, 74.2 years; 52.3% women) were prospectively followed over 9 years in the Health, Aging and Body Composition study. Arterial stiffness was measured as pulse wave velocity (PWV) and analyzed in tertiles. Cognitive function was assessed using the Modified Mini-Mental State Exam (3MS) at baseline and repeated at years 3, 5, 8 and 10. Lower 3MS scores indicate worse function. We fit linear mixed models to examine longitudinal changes in cognitive function over the 9 years of follow-up and logistic regression models, restricted to 1,331 participants, to examine cognitive impairment defined as a decrease of ≥5 points after 9 years. We adjusted for socio-demographics, Apoe4 and CVD risk factors.
Results
The annual decrease in 3MS scores was 0.30 points at low PWV (95%CI=−0.37;-0.22), 0.46 points at middle PWV (95%CI=−0.54;-0.39) and 0.45 points at high PWV (95%CI=−0.53;-0.38), from fully-adjusted linear mixed models. In fully-adjusted models, the odds of cognitive impairment after 9 years of follow-up was 40% greater for subjects with middle PWV (OR=1.40; 95% CI=1.03; 1.92) and 59% greater for subjects with high PWV (OR=1.59; 95% CI=1.16; 2.18), compared to low PWV.
Conclusions
High arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline.
doi:10.1161/STROKEAHA.112.673533
PMCID: PMC3572783  PMID: 23321445
8.  Kidney Function and Mortality in Octogenarians: Cardiovascular Health Study All Stars 
OBJECTIVES:
To examine the association between kidney function and all-cause mortality in octogenarians.
DESIGN:
Retrospective analysis of prospectively collected data.
SETTING:
Community.
PARTICIPANTS:
Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.
MEASUREMENTS:
Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFRCR) and cystatin C one-variable (eGFRCYS) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.
RESULTS:
Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFRCR and all-cause mortality was U-shaped. In comparison with the reference quintile (64–75 mL/min per 1.73 m2), the highest (≥75 mL/min per 1.73 m2) and lowest (≤43 mL/min per 1.73 m2) quintiles of eGFRCR were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36–4.55; HR = 2.28, 95% CI = 1.26–4.10, respectively). The association between eGFRCYS and all-cause mortality was linear in those with eGFRCYS of less than 60 mL/min per 1.73 m2, and in the multivariate analyses, the lowest quintile of eGFRCYS (<52 mL/min per 1.73 m2) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12–3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m2).
CONCLUSION:
Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFRCR and all-cause mortality differed from that observed with eGFRCYS; the relationship was U-shaped for eGFRCR, whereas the risk was primarily present in the lowest quintile for eGFRCYS. J Am Geriatr Soc 2012.
doi:10.1111/j.1532-5415.2012.04046.x
PMCID: PMC3902776  PMID: 22724391
octogenarians; kidney function; mortality
9.  AORTIC PULSE WAVE VELOCITY PREDICTS FOCAL WHITE MATTER HYPERINTENSITIES IN A BIRACIAL COHORT OF OLDER ADULTS 
Hypertension  2012;61(1):160-165.
While the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, its less clear if these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics and associations are stronger within watershed areas.
Neuroimaging was obtained in 2006–08 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity measures in 1997–98. Multivariable regression models estimated the coefficients for pulse wave velocity (cm/sec) in relationship to presence, severity and spatial distribution of white matter hyperintensities, gray matter volume and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors and diseases from 1997–98 to 2006–08.
Higher pulse wave velocity in 1997–98 was associated with greater white matter hyperintensities volume in 2006–08 within the left superior longitudinal fasciculus (age and total brain white matter hyperintensities-adjusted p=0.023), but not with white matter hyperintensities in other tracts, or with fractional anisotropy or gray matter volume from total brain (p>0.2). Associations were stronger in blacks than in whites remaining significant in fully adjusted models.
Elderly with white matter hyperintensities in tracts related to processing speed and memory are more likely to have had higher pulse wave velocity values ten years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly.
doi:10.1161/HYPERTENSIONAHA.112.198069
PMCID: PMC3521843  PMID: 23172923
pulse wave velocity; small vessel disease; longitudinal; fractional anisotropy; community-dwelling elderly
10.  Plasma Beta Amyloid Level and Depression in Older Adults 
Background.
Older adults with depression have an increased risk of developing dementia. Low plasma beta-amyloid 42 (Aβ42) and Aβ42/Aβ40 have emerged as promising biomarkers of dementia. The association between depression and plasma Aβ is unclear.
Methods.
In this longitudinal study of 988 community-dwelling elders from the Health Aging and Body Composition study, depression was assessed with the Center for Epidemiologic Studies-Depression Scale 10-item version. We determined the association between Aβ42 and Aβ42/Aβ40 tertile and depression at baseline and over 9 years. We also stratified the models to determine if apolipoprotein E e4 allele status modified the associations.
Results.
Mean baseline age was 74.0 ± 3.0 years, 51 (5.2%) participants had depression, 545 (55.2%) were women, 531 (53.7%) were black, and 286 (30.7%) had one or more apolipoprotein E e4 allele. At baseline, there was no association between Aβ42/Aβ40 or Aβ42 and depression. Over 9 years, 220 (23.5%) participants developed depression. In adjusted Cox proportional hazards models, among those with one or more e4 allele, low Aβ42/Aβ40 was associated with an increased risk of developing depression over time (low 10.8% vs high 3.2%, hazard ratio = 2.38, 95% confidence interval: 1.15–4.92). Among those with no e4 allele, there was no association between Aβ42/Aβ40 and risk of depression over time (13.3% vs 17.5%, hazard ratio = 0.80, 95% confidence interval: 0.52–1.23; p value for interaction = .003).
Conclusions.
The association between low plasma Aβ42/Aβ40 and increased risk of incident depression among those with one or more apolipoprotein E e4 allele implies a synergistic relationship similar to that found with dementia. Future work should investigate the interrelationships among plasma Aβ42/Aβ40, depression, and dementia.
doi:10.1093/gerona/gls093
PMCID: PMC3598362  PMID: 22499763
Depression; Epidemiology; Plasma beta amyloid
11.  A variant of sparse partial least squares for variable selection and data exploration 
When data are sparse and/or predictors multicollinear, current implementation of sparse partial least squares (SPLS) does not give estimates for non-selected predictors nor provide a measure of inference. In response, an approach termed “all-possible” SPLS is proposed, which fits a SPLS model for all tuning parameter values across a set grid. Noted is the percentage of time a given predictor is chosen, as well as the average non-zero parameter estimate. Using a “large” number of multicollinear predictors, simulation confirmed variables not associated with the outcome were least likely to be chosen as sparsity increased across the grid of tuning parameters, while the opposite was true for those strongly associated. Lastly, variables with a weak association were chosen more often than those with no association, but less often than those with a strong relationship to the outcome. Similarly, predictors most strongly related to the outcome had the largest average parameter estimate magnitude, followed by those with a weak relationship, followed by those with no relationship. Across two independent studies regarding the relationship between volumetric MRI measures and a cognitive test score, this method confirmed a priori hypotheses about which brain regions would be selected most often and have the largest average parameter estimates. In conclusion, the percentage of time a predictor is chosen is a useful measure for ordering the strength of the relationship between the independent and dependent variables, serving as a form of inference. The average parameter estimates give further insight regarding the direction and strength of association. As a result, all-possible SPLS gives more information than the dichotomous output of traditional SPLS, making it useful when undertaking data exploration and hypothesis generation for a large number of potential predictors.
doi:10.3389/fninf.2014.00018
PMCID: PMC3939647  PMID: 24624079
high-dimensional; multicollinearity; over-fitting; SPLS; inference; tuning parameters; network; MRI
12.  Weight, mortality, years of healthy life and active life expectancy in older adults 
Journal of the American Geriatrics Society  2007;56(1):10.1111/j.1532-5415.2007.01500.x.
Objective
Two-thirds of older adults are currently classified as overweight or obese. Given that the importance of these weight categories was documented primarily in middle-aged persons, the survival and health status consequences for older adults are controversial. Here, we explore the issue of whether weight categories predict subsequent mortality and morbidity in older adults.
Design, Setting, and Participants
Data came from the Cardiovascular Health Study, a population-based cohort study of 5888 older adults.
Measurements
We estimated the age- and sex-specific probabilities of transition from one health state to another and from one weight category to another. From these probabilities we estimated future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65.
Results
Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese, and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than normal weight, while overweight and obesity were rarely worse than normal weight, and were sometimes associated with significantly better outcomes.
Conclusions
Similar to middle-aged populations, older adults are likely to be or to become overweight or obese. However, higher weight is not associated with worse health in this age group. Thus, the number of older adults at a “healthy” weight may be much higher than currently believed.
doi:10.1111/j.1532-5415.2007.01500.x
PMCID: PMC3865852  PMID: 18031486
self-rated health; equilibrium; activities of daily living; years of healthy life; active life expectancy; multi-state life tables; older adults
13.  Age-specific Prevalence and Years of Healthy Life in a System with 3 Health States 
Statistics in medicine  2008;27(9):10.1002/sim.3056.
Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an “equilibrium” value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate when a valid survival table was known from other sources, or when the available data were sufficient to estimate survival accurately. Performance was better with fewer waves of data. If validated in other situations, these equilibrium estimates of prevalence and years of healthy life (YHL) and their standard errors may be useful when the goal is to compare YHL for different populations.
doi:10.1002/sim.3056
PMCID: PMC3865856  PMID: 17847058
self-rated health; years of healthy life; prevalence; multi-state lifetable; variance for area under the curve; Sullivan method
14.  Hemoglobin Decline, Function and Mortality in the Elderly: The Cardiovascular Health Study 
American journal of hematology  2012;88(1):10.1002/ajh.23336.
Background
While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied.
Methods
We evaluated the determinants and consequences of hemoglobin decline in 3.758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ≥65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: 1) per each 1g/dL decrease in hemoglobin and 2) development of anemia by the WHO criteria.
Results
Among participants without baseline anemia, hemoglobin decreased by 0.4g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1g/dL decrease) predicted subsequent mortality in men and women.
Conclusions
Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life.
doi:10.1002/ajh.23336
PMCID: PMC3860593  PMID: 23044913
Anemia; Hemoglobin; Elderly; Mortality; Function; Epidemiology
15.  Antihypertensive Drug Class Use and Differential Risk of Urinary Incontinence in Community-Dwelling Older Women 
Background.
Medication use is a potentially reversible cause of urinary incontinence (UI). The objective of this longitudinal cohort study was to evaluate whether self-reported UI in community-dwelling older women is associated with the use of different classes of antihypertensive agents.
Methods.
The sample consisted of 959 black and white women aged 72–81 years without baseline (Year 1) UI from the Health, Aging, and Body Composition Study. Use of any antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta blockers, calcium channel blockers, diuretics [loop], diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was determined during Year 3 in-person interviews. The number of unique antihypertensive agents used and the standardized daily dosage were also examined. Self-reported UI, operationally defined as leaking urine at least weekly during the previous 12 months, was assessed at Year 4 visits.
Results.
A total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive use, number of agents used, and standardized daily dosage at Year 3 were not associated with UI at Year 4, use of one particular drug class—peripheral alpha blockers (ie, doxazosin, prazosin, and terazosin)—was associated with fourfold greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79–11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence interval = 1.78–43.53; p = .0076).
Conclusion.
In community-dwelling older women, peripheral alpha blocker use was associated with UI, and the odds nearly doubled when used with loop diuretics.
doi:10.1093/gerona/gls177
PMCID: PMC3636671  PMID: 22972942
16.  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.
doi:10.1093/gerona/gls123
PMCID: PMC3636673  PMID: 22546961
Aging; Index; Mortality; Disability; Longevity
17.  The Association of Menopausal Status with Physical Function: The Study of Women’s Health Across the Nation (SWAN) 
Menopause (New York, N.Y.)  2012;19(11):1186-1192.
Objective
To determine if post-menopausal status is associated with self-reported limitations in physical function.
Methods
SWAN is a multi-site, multi-ethnic, longitudinal study of midlife women. Women aged 45–57 years (N=2,566) completed the Medical Outcomes Study Short-Form Physical Function Scale at visit 4 (2000–2001); scores created a 3-category variable of physical function limitations: none (86–100), moderate (51–85) and substantial (0–50). Menopausal status in SWAN is a 5-category list variable based on menstrual bleeding patterns and gynecological surgery. Pre-and peri-menopausal women using hormones (n=284) or missing physical function scores (n=46) were excluded. Multinomial logistic regression was used to relate physical function and menopausal status adjusting for age, ethnicity, site, education, body mass index (BMI), self-reported diabetes, hypertension, arthritis, depressive symptoms, smoking and hormone use among postmenopausal women.
Results
Of 2,236 women, 8% were pre-, 51% early peri-, 12% late peri-, 24% natural post-, and 5% surgical post-menopausal status. In the full model, substantial limitations in physical function were higher in post-menopausal compared to pre-menopausal women whether it occurred naturally (OR 3.82; 95% CI: 1.46–10.0) or surgically (OR 3.54; 95% CI: 1.15–10.84). These associations were attenuated by higher BMI and depressive symptoms, but remained significant. Moderate limitations in physical function were not significantly related to menopausal status.
Conclusion
Women with surgical or naturally occurring post-menopause reported greater limitations in physical function than pre-menopausal women, independent of age, only partly explained by higher BMI and depressive symptoms. This suggests that physiologic changes of menopause could contribute directly to limitations in physical function.
doi:10.1097/gme.0b013e3182565740
PMCID: PMC3526111  PMID: 22760087
Physical functioning; Functional limitations; Menopause; Menopausal status; SF-36
18.  Racial Differences in Antilipemic Use and Lipid Control in High Risk Older Adults Post Medicare Part D 
American heart journal  2013;166(4):792-797.
Background
Older blacks are less likely to receive guideline-recommended antilipemic therapy and achieve lipid control than older whites due in part to out-of-pocket costs. We sought to determine whether racial differences in antilipemic use and lipid control narrowed after Medicare Part D’s implementation.
Methods
This before-after study included 1091 black and white adults age >70 with coronary heart disease and/or diabetes mellitus from the Health Aging and Body Composition Study. Primary outcomes were antilipemic use and LDL-C control. Key independent variables were race, time (pre- vs. post-Part D), and their interaction.
Results
Before Part D, fewer blacks than whites reported taking an antilipemic (32.70% vs 49.35%) and this difference was sustained after Part D (blacks 48.30% vs whites 64.57%). Multivariable generalized estimating equations confirmed no post Part D change in racial differences in antilipemic use (adjusted ratio of the odds ratios [AROR] 1.07, 95% CI 0.79–1.45). Compared to whites, more blacks had poor lipid control both before Part D (24.30% vs 12.36% respectively) and after Part D (24.46% vs 13.72% respectively), with no post Part D change in racial differences in lipid control (AROR 0.82, 95% CI 0.51–1.33).
Conclusion
While antilipemic use increased after Medicare Part D for both races, this policy change was associated neither with a change in lipid control for either racial group nor in the racial differences in antilipemic use or lipid control.
doi:10.1016/j.ahj.2013.07.001
PMCID: PMC3801224  PMID: 24093862
19.  Families Enriched for Exceptional Longevity also have Increased Health-Span: Findings from the Long Life Family Study 
Hypothesizing that members of families enriched for longevity delay morbidity compared to population controls and approximate the health-span of centenarians, we compared the health-spans of older generation subjects of the Long Life Family Study (LLFS) to controls without family history of longevity and to centenarians of the New England Centenarian Study (NECS) using Bayesian parametric survival analysis. We estimated hazard ratios, the ages at which specific percentiles of subjects had onsets of diseases, and the gain of years of disease-free survival in the different cohorts compared to referent controls. Compared to controls, LLFS subjects had lower hazards for cancer, cardiovascular disease, severe dementia, diabetes, hypertension, osteoporosis, and stroke. The age at which 20% of the LLFS siblings and probands had one or more age-related diseases was approximately 10 years later than NECS controls. While female NECS controls generally delayed the onset of age-related diseases compared with males controls, these gender differences became much less in the older generation of the LLFS and disappeared amongst the centenarians of the NECS. The analyses demonstrate extended health-span in the older subjects of the LLFS and suggest that this aging cohort provides an important resource to discover genetic and environmental factors that promote prolonged health-span in addition to longer life-span.
doi:10.3389/fpubh.2013.00038
PMCID: PMC3859985  PMID: 24350207
health-span; longevity; onset of disease; survival analysis; Weibull regression
20.  Genetic Analysis of Serum Osteocalcin and Bone Mineral in Multigenerational Afro-Caribbean Families 
Purpose
Osteocalcin (OC) is a protein constituent of bone matrix and a marker of bone formation. We characterized the heritability of serum OC measures and identified genomic regions potentially involved in the regulation of OC via high-density genome-wide linkage analysis in African ancestry individuals.
Methods
African ancestry individuals (n=459) were recruited, without regard to health status, from seven probands (mean family size = 66; 4,373 relative pairs). Residual heritability of serum OC measures was estimated and multipoint quantitative trait linkage analysis was performed using pedigree-based maximum likelihood methods.
Results
Residual heritabilities of total OC, uncarboxylated OC, carboxylated OC and percent uncarboxylated OC were: 0.74±0.10, 0.89±0.08, 0.46±0.10 and 0.41±0.09, respectively. All OC measures were genetically correlated with whole body bone mineral content (BMC). We obtained strong evidence of bivariate linkage for percent uncarboxylated OC and whole body BMC on chromosome 17 (LOD=3.15, 99cM).
Conclusions
All forms of OC were highly heritable and genetically correlated with total body BMC in these African ancestry families. The identified linkage region contains several candidate genes for bone and energy metabolism including COL1A1 and TNFRSF11A. Further studies of this genomic region may reveal novel insight into the genetic regulation of OC and bone mineralization.
doi:10.1007/s00198-011-1763-2
PMCID: PMC3768139  PMID: 21935688
osteocalcin; genome-wide linkage; African ancestry; bone mineral
21.  Physical Performance and Subsequent Disability and Survival in Older Adults with Malignancy: Results from the Health, Aging and Body Composition Study 
OBJECTIVES
To evaluate objective physical performance measures as predictors of survival and subsequent disability in older patients with cancer.
DESIGN
Longitudinal cohort study.
SETTING
Health, Aging and Body Composition (Health ABC) Study.
PARTICIPANTS
Four hundred twenty-nine individuals diagnosed with cancer during the first 6 years of follow-up of the Health ABC Study.
MEASUREMENTS
The associations between precancer measures of physical performance (20-m usual gait speed, 400-m long-distance corridor walk (LDCW), and grip strength) and overall survival and a short-term outcome of 2-year progression to disability or death were evaluated. Cox proportional hazards and logistic regression models, stratified for metastatic disease, respectively, were used for outcomes.
RESULTS
Mean age was 77.2, 36.1% were women, and 45.7% were black. Faster 20-m usual walking speed was associated with a lower risk of death in the metastatic group (hazard ratio = 0.89, 95% confidence interval (CI) = 0.79–0.99) and lower 2-year progression to disability or death in the nonmetastatic group (odds ratio (OR) = 0.77, 95% CI = 0.64–0.94). Ability to complete the 400-m LDCW was associated with lower 2-year progression to disability or death in the nonmetastatic group (OR = 0.24, 95% CI = 0.10–0.62). There were no associations between grip strength and disability or death.
CONCLUSION
Lower extremity physical performance tests (usual gait speed and 400-m LDCW) were associated with survival and 2-year progression to disability or death. Objective physical performance measures may help inform pretreatment evaluations in older adults with cancer.
doi:10.1111/j.1532-5415.2009.02620.x
PMCID: PMC3760384  PMID: 20122042
physical performance; elderly; cancer; disability; survival
22.  Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly 
Biochimica et Biophysica Acta  2012;1817(9):1691-1700.
The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondrial genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL. These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life.
doi:10.1016/j.bbabio.2012.05.012
PMCID: PMC3389152  PMID: 22659402
metabolic rate; energy expenditure; mitochondria; mtDNA; oxidative phosphorylation; DNA sequencing
23.  Shorter telomeres are associated with obesity and weight gain in the elderly 
Objective
Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.
Design
Levels of adiposity were assessed in 6 ways (obesity status, body mass index or BMI, the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2,721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline and 3 of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.
Results
At baseline, TL was negatively associated with % body fat (β = −0.35 ± 0.09, p = 0.001) and subcutaneous fat (β = −2.66 ± 1.07, p = 0.01), and positively associated with leptin after adjusting for % body fat (β = 0.32 ± 0.14, p = 0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (β = 0.48 ± 0.20, p = 0.01) and % body fat (β = 0.42 ± 0.23, p = 0.05).
Conclusion
Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and warrant more prospective studies.
doi:10.1038/ijo.2011.196
PMCID: PMC3408817  PMID: 22005719
Obesity; telomere length; adiposity; telomeres
24.  Long-term Assessment of Inflammation and Healthy Aging in Late Life: The Cardiovascular Health Study All Stars 
Background.
Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging.
Methods.
We examined associations of long-term change in C-reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality in 1,051 participants in the Cardiovascular Health Study All Stars Study. Biomarkers were measured in 1996–1997 and 2005–2006.
Results.
In 2005–2006, median age was 84.9 years, 63% were women and 17% non-white; 21% had at least a doubling in CRP over time and 23% had at least a doubling in IL-6. Adjusting for demographics, CVD risk factors, and 1996–1997 CRP level, each doubling in CRP change over 9 years was associated with higher risk of physical or cognitive impairment (odds ratio 1.29; 95% confidence interval 1.15, 1.45). Results were similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not CRP, was associated with incident CVD events; hazard ratio (95% confidence interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16, 1.65]). In models containing both change and 2005–2006 level, only level was associated with CVD events and mortality.
Conclusions.
Although increases in inflammation markers over 9 years were associated with higher concurrent risk of functional impairment and subsequent CVD events and mortality, final levels of each biomarker appeared to be more important in determining risk of subsequent events than change over time.
doi:10.1093/gerona/glr261
PMCID: PMC3436091  PMID: 22367431
Inflammation; Aging; Physical function; Cognitive function
25.  Patterns of Focal Gray Matter Atrophy Are Associated With Bradykinesia and Gait Disturbances in Older Adults 
Objectives.
Identify the neuroimaging correlates of parkinsonian signs in older adults living in the community.
Methods.
Magnetic resonance imaging was obtained in 307 adults (82.9 years, 55% women, 39% blacks) concurrently with the Unified Parkinson Disease Rating scale—motor part. Magnetic resonance imaging measures included volume of whole-brain white matter hyperintensities and of gray matter for primary sensorimotor, supplementary motor, medial temporal areas, cerebellum, prefronto-parietal cortex, and basal ganglia.
Results.
About 25% of the participants had bradykinesia, 26% had gait disturbances, and 12% had tremor. Compared with those without, adults with any one of these signs were older, walked more slowly, had worse scores on tests of cognition, mood and processing speed, and higher white matter hyperintensities volume (all p ≤ .002). Gray matter volume of primary sensorimotor area was associated with bradykinesia (standardized odds ratio [95% confidence interval]: 0.46 [0.31, 0.68], p < .0001), and gray matter volume of medial temporal area was associated with gait disturbances (0.56 [0.42, 0.83], p < .0001), independent of white matter hyperintensities volume and age. Further adjustment for measures of muscle strength, cardiovascular health factors, cognition, processing speed, and mood or for gait speed did not substantially change these results.
Conclusions.
Atrophy within primary sensorimotor and medial temporal areas might be important for development of bradykinesia and of gait disturbances in community-dwelling elderly adults. The pathways underlying these associations may not include changes in white matter hyperintensities volume, cognition, information processing speed, mood, or gait speed.
doi:10.1093/gerona/glr262
PMCID: PMC3436092  PMID: 22367436
Bradykinesia; Gait disturbances; Brain MRI

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