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.
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.
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).
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.
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.
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.
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).
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.
osteocalcin; genome-wide linkage; African ancestry; bone mineral
To evaluate objective physical performance measures as predictors of survival and subsequent disability in older patients with cancer.
Longitudinal cohort study.
Health, Aging and Body Composition (Health ABC) Study.
Four hundred twenty-nine individuals diagnosed with cancer during the first 6 years of follow-up of the Health ABC Study.
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.
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.
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.
physical performance; elderly; cancer; disability; survival
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.
metabolic rate; energy expenditure; mitochondria; mtDNA; oxidative phosphorylation; DNA sequencing
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.
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.
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).
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.
Obesity; telomere length; adiposity; telomeres
Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging.
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.
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.
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.
Inflammation; Aging; Physical function; Cognitive function
Identify the neuroimaging correlates of parkinsonian signs in older adults living in the community.
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.
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.
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.
Bradykinesia; Gait disturbances; Brain MRI
Although there is evidence linking smoking and heart failure (HF), the association between lifetime smoking exposure and HF in older adults and the strength of this association among current and past smokers is not well known.
We examined the association between smoking status, pack-years of exposure and incident HF risk in 2, 125 participants of the Health, Aging, and Body Composition Study (age 73. 6±2. 9 years; 69. 7% females; 54. 2% whites)using proportional hazard models.
At inception, 54. 8% of participants were non-smokers, 34. 8% were past smokers, and 10. 4% were current smokers. During follow-up (median, 9. 4 years), HF incidence was 11. 4 per 1000 person-years in non-smokers, 15. 2 in past smokers (hazard ratio [HR] vs. non-smokers 1. 33; 95% confidence interval [CI] 1. 01, 1. 76; p=0. 045), and 21. 9 in current smokers (HR 1. 93; 95% CI 1. 30, 2. 84; p=0. 001). After adjusting for HF risk factors, incident coronary events, and competing risk for death, a dose-effect association between pack-years of exposure and HF risk was observed (HR 1. 09; 95% CI 1. 05, 1. 14; p<0. 001 per 10 pack-years). HF risk was not modulated by pack-years of exposure in current smokers. In past smokers, HR for HF was 1. 05 (95% CI, 0. 64, 1. 72) for 1–11 pack-years; 1. 23 (95% CI, 0. 82, 1. 83) for 12–35 pack-years; and 1. 64 (95% CI, 1. 11, 2. 42) for >35 pack-years of exposure in fully adjusted models (p<0. 001 for trend) compared to non-smokers.
In older adults, both current and past cigarette smoking increase HF risk. In current smokers, this risk is high irrespective of pack-years of exposure, whereas in past smokers there was a dose-effect association.
Maintaining cognitive function protects older adults from developing functional decline. This study aims to identify the neuroimaging correlates of maintenance of higher global cognition as measured by the Modified Mini Mental State Test (3MS) score.
Repeated 3MS measures from 1997–98 through 2006–07 and magnetic resonance imaging with diffusion tensor in 2006–07 were obtained in a biracial cohort of 258 adults free from dementia (mean age 82.9 years, 56% women, 42% blacks). Participants were classified as having shown either maintenance (3MS slope>0) or decline (3MS slopeb1 SD below the mean) of cognition using linear mixed models. Measures of interest were white matter hyperintensity volume (WMHv) from total brain, volume of the gray matter (GMv) and microstructure (mean diffusivity, MD) for total brain and for brain areas known to be related to memory and executive control function: medial temporal area (hippocampus, parahippocampus and entorhinal cortex), cingulate cortex, dorsolateral prefrontal and posterior parietal cortex.
Differences between cognitive maintainers (n=153) and non-maintainers (n=107) were significant for GMv of the medial temporal area (35.8%, p=0.004) and lower MD of the cingulate cortex (37.9%, p=0.008), but not for other neuroimaging markers. In multivariable regression models adjusted for age, race, WMHv and GMV from the total brain and vascular conditions, each standard deviation of GMv of the medial temporal area and each standard deviation of MD of the cingulate cortex were associated with a nearly 4 times greater probability (odds ratio [standard deviation]: 3.80 [1.16, 12.44]) and a 34% lower probability (0.66, [0.46, 0.97]) of maintaining cognitive function, respectively. In these models neither WMHv nor GMv from total brain were significantly associated with probability of maintaining cognitive function.
Preserving the volume of the medial temporal area and the microstructure of the cingulate cortex may contribute to maintaining cognitive function late in life.
Background and Purpose
Mobility disability is a serious and frequent adverse health outcome associated with aging. Early identification of individuals at risk for mobility disability is important if interventions to prevent disability are to be instituted. The objectives of this prospective study were to: 1) determine the magnitude of stance time variability (STV) that discriminates individuals who currently have mobility disability (prevalent mobility disability) and 2) determine the magnitude of STV that predicts a new onset of mobility disability at one year (incident mobility disability).
552 community-dwelling older adults were evaluated as part of the Cardiovascular Health Study, a longitudinal cohort study. Stance time, in milliseconds (ms), was determined from 2 passes on a 4-meter computerized walkway at self-selected walking speed, and STV was defined as the standard deviation (SD) from approximately 12 individual steps. Mobility disability was defined as self-reported difficulty walking a half mile. Receiver operating characteristic (ROC) curves were plotted to determine an optimal cutoff value for stance time variability for prevalent and incident mobility disability, and the area under the ROC curve was computed.
The optimal cut-off score for STV (maximizing sensitivity and specificity) for prevalent mobility disability was 0.037 sec(sensitivity = 65%, specificity = 65%, AUC = 0.70) and for incident 1 year mobility disability was 0.034 sec(sensitivity = 61%, specificity = 60%, AUC = 0.65). The use of likelihood ratios demonstrated a gradient of risk across values of STV, with mobility risk increasing as values of STV increased.
Discussion and Conclusion
Values of STV may be useful in identifying older adults with mobility disability and at risk for future disability. We recommend the more conservative estimate for identifying risk, STV=0.034 s, which maximizes the sensitivity and minimizes false negatives. The relatively modest values on the validity indices could possibly be improved by increasing the reliability of the measurement of STV. Clinicians should interpret the cut-off values liberally and use STV in conjunction with other measures until further work is completed to validate STV as an indicator of mobility disability.
Gait variability; Disability; Sensitivity; Specificity; Older Adults
Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown if the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults.
Data was analyzed from the Health, Aging, and Body Composition Study, a prospective cohort of 3,075 community-dwelling US adults.
2,119 participants with measured TSH and data on metabolic syndrome components were included in the analysis.
TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria.
At baseline, 684 participants met criteria for metabolic syndrome. At 6yr follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR 1.03, 95% CI 1.01–1.06, p=0.02), and the association was stronger for TSH within the normal range (OR 1.16, 95% CI 1.03–1.30, p=0.02). Subclinical hypothyroidism with a TSH>10mIU/L was significantly associated with increased odds of prevalent metabolic syndrome (OR 2.3, 95% CI 1.0–5.0, p=0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6–7.5).
Higher TSH levels and subclinical hypothyroidism with a TSH>10 mIU/L are associated with increased odds of prevalent but not incident metabolic syndrome.
Thyroid Function; Metabolic Syndrome; Subclinical Hypothyroidism
Inflammation, oxidative damage, and platelet activation are hypothesized biological mechanisms driving the disablement process. The aim of the present study is to assess whether biomarkers representing these mechanisms predicted major adverse health-related events in older persons.
Data are from 2,234 community-dwelling nondisabled older persons enrolled in the Health Aging and Body Composition study. Biomarkers of lipid peroxidation (ie, urinary levels of 8-iso-prostaglandin F2α), platelet activation (ie, urinary levels of 11-dehydro-thromboxane B2), and inflammation (serum concentrations of interleukin-6) were considered as independent variables of interest and tested in Cox proportional hazard models as predictors of (severe) mobility disability and overall mortality.
The sample’s (women 48.0%, whites 64.3%) mean age was 74.6 (SD 2.9) years. During the follow-up (median 11.4 years), 792 (35.5%), 269 (12.0%), and 942 (42.2%) events of mobility disability, severe mobility disability, and mortality occurred, respectively. Only interleukin-6 showed significant independent associations with the onset of all the study outcomes. Higher levels of urinary 8-iso-prostaglandin F2α and 11-dehydro-thromboxane B2 independently predicted increased risk of death (hazard ratio 1.10, 95% confidence interval 1.03–1.19 and hazard ratio 1.14, 95% confidence interval 1.06–1.23, respectively). No significant interactions of gender, race, cardiovascular disease, diabetes, and antiplatelet drugs were detected on the studied relationships.
The inflammatory marker interleukin-6 is confirmed to be a robust predictor for the onset of negative health-related events. Participants with higher urinary levels of 8-iso-prostaglandin F2α and 11-dehydro-thromboxane B2 presented a higher mortality risk.
Oxidative damage; Platelet activation; Inflammation; Disability; Mortality
Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms.
Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (≥13 μmol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up.
At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5–19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms.
High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.
Vitamin B12; Homocysteine; Peripheral nerve function; Neurological signs
Not all cigarette smokers develop chronic obstructive pulmonary disease (COPD), and discovering susceptibility factors is an important research priority. The oxidative burden of smoking may overwhelm antioxidant defenses, and vulnerabilities may exist as a result of sequence variants in genes encoding antioxidant enzymes. This study explored the association between genetic variation in a network of antioxidant enzymes and lung phenotypes. Linear models evaluated single locus marker associations in 2,387 European and African American participants in the Health, Aging, and Body Composition (Health ABC) Study. After correcting for multiple comparisons, 15 statistically significant associations were identified, all of which were for SNP by smoking interactions. The most statistically significant findings were in genes encoding members of the isocitrate dehydrogenase gene family (IDH3A, IDH3B, IDH2). For rs6107100 (IDH3B) the variant genotype was associated with a difference of 6% in the FEV1/FVC ratio in African American current smokers, but the SNP had little or no association with FEV1/FVC in former and never smokers (nominal pinteraction=5 × 10−6). A variant in peroxiredoxin gene (rs9787810, PRDX5) was associated with lower %predicted FEV1 and a lower ratio in European American current smokers, with little or no association in other smoking groups (nominal pinteraction=0.0001 and 0.0003, respectively). The studied genes have not been reported in previous candidate gene association studies, and thus the findings suggest novel mechanisms and targets for future research, and provide evidence for a contribution of sequence variation in genes encoding antioxidant enzymes to susceptibility in smokers.
Antioxidant enzymes; Lung function
To determine the relative effect of five chronic conditions on four representative universal health outcomes.
Cardiovascular Health Study.
Five thousand two hundred and ninety-eight community-living participants aged 65 and older.
Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death.
Each condition adversely affected self-rated health (P<.001) and ADLs and IADLs (P<.001). For example, persons with HF performed 0.70 ± 0.08 fewer ADLs and IADLs than those without; persons with depression and persons with cognitive impairment performed 0.59 ± 0.04 and 0.58 ± 0.06 fewer activities, respectively, than those without these conditions. Depression, HF, COPD, and osteoarthritis were associated with 1.18 ± 0.04, 0.40 ± 0.08, 0.40 ± 0.05, and 0.57 ± 0.03 more symptoms, respectively, in individuals with these conditions than in those without. HF (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 1.97–4.10), COPD (2.62, 95% CI = 1.94–3.53), cognitive impairment (2.05, 95% CI = 1.47–2.85), and depression (1.47, 95% CI = 1.08–2.01) were each associated with death within 2 years. Several paired combinations of conditions had synergistic effects on ADLs and IADLs. For example, individuals with HF plus depression performed 2.0 fewer activities than persons with neither condition, versus the 1.3 fewer activities expected from adding the effects of the two conditions together.
Universal health outcomes may provide a common metric for measuring the effects of multiple conditions and their treatments. The varying effects of the conditions across universal outcomes could inform care priorities.
multiple chronic conditions; patient-reported outcomes; universal health outcomes
Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression).
LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima–media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black).
Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (β [SE] = −132  bp, p < .01), age (β [SE] = −107 , p = .02) or carotid thickness (β [SE] = −95  bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%.
LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age.
Leukocyte telomere length; Disease burden; Noninvasive measurements; Aging
Increased antioxidant defenses are hypothesized to decrease age- and smoking-related decline in lung function.
The relation of dietary antioxidants, smoking, and forced expiratory volume in the 1st second of effort (FEV1) was investigated in community-dwelling older adults in the Health, Aging, and Body Composition Study. 1,443 participants completed a food frequency questionnaire, self-reported smoking history, and had measurements of FEV1 at both baseline and after 4 years of follow-up. The association of dietary intake of nutrients and foods with antioxidant properties and rate of FEV1 decline was investigated using hierarchical linear regression models.
In continuing smokers (current smokers at both time points), higher vitamin C and higher intake of fruits and vegetables were associated with an 18 and 24 ml/year slower rate of FEV1 decline compared to lower intake (P<0.0001 and 0.003, respectively). In quitters (current smoker at study baseline, quit during follow-up), higher intake was associated with an attenuated rate of decline for each nutrient studied (p<0.003, all models). In non-smoking participants, there was little or no association of diet and rate of decline in FEV1.
The intake of nutrients with antioxidant properties may modulate lung function decline in older adults exposed to cigarette smoke.
Aging; Dietary Intake; Lung Function Measurements; Oxidants/Antioxidants; Smoking and Health
Type 2 diabetes is a risk factor for PAD, and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by 2 methods. PAD was first defined as the development of an abnormal ankle brachial index (ABI) (dichotomous outcome) after six years of follow-up. PAD was alternatively defined as the development of clinical PAD (time to event analysis). The study samples included adults over the age of 65 who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, BMI, smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n=2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (Odds Ratio=1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval 1.20-2.71). In the clinical PAD analysis (n=4208), we found a similar relation (Hazard ratio=2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.
Peripheral artery disease; Diabetes; Insulin Resistance; Epidemiology
Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age—62 years, moderate CP—43% and severe CP—17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10−6) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)—NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28–1.73, P = 3.5 × 10−7))]; moderate CP (n = 2293)—NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24–1.59, P = 7.5 × 10−8), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52–2.65, P = 8.2 × 10−7). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10−9) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.
Background: the rate of performance decline may influence the risk of disability or death.
Methods: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998–99, and the rate of performance change between 1992–93 and 1998–99, to the risk of death or disability in 2005–06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992–93 and 1998–99.
Results: participants’ age averaged 79.4 in 1998–99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95% CI: 1.16 –1.96) and a 1.27 RR of death (95% CI: 1.07 –1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35% (95% CI: 1.13 –1.61) and death by 31% (95% CI: 1.16 –1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF.
Conclusion: performance trajectories independently predict death and disability.
ageing; motor skills; activities of daily living; disabled persons; mortality; elderly
Studies demonstrate existence of inflammation in prevalent Parkinson’s disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study.
Blood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor–α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases.
Risk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR] = 1.5, 95% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95% CI: 0.2, 0.8).
Although inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset.
albumins; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson’s disease; tumor necrosis factor-α
Retinal microvascular signs are associated with systemic conditions and cognitive decline. We studied the associations of microvascular changes, measured by retinal signs, with disability in performing activities of daily living (ADL).
Prospective cohort study.
1487 participants in the Cardiovascular Health Study (mean age 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness (IMT) at the 1998–99 visit.
Main Outcome Measure
Incident ADL disability, defined as self-reported difficulty in performing any ADLs, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid IMT ≥ 80th percentile or ≥ 25% stenosis; and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood that are symptoms of frontal subcortical dysfunction.
During the median follow-up of 3.1 years (maximum 7.8 years), participants with ≥ 2 retinal signs had a higher rate of disability than those with < 2 retinal signs (10.1% versus 7.1%; adjusted hazards ratio, 1.45; 95% confidence interval, 1.24–1.69; P < 0.001). There was no evidence of interaction by advanced carotid atherosclerosis (P > 0.10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms, but not by cerebral microvascular disease on brain imaging.
These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best utilize retinal photography in the clinical risk prediction.
Longitudinal studies have contributed substantially to understanding of aging and geriatric syndromes. These efforts have provided a base of knowledge of the critical factors to consider in designing and implementing new longitudinal studies in older adults. This review highlights some of the major considerations in planning and implementing this type of study. Longitudinal studies can assess change over time and specific disease endpoints. Such projects require multidisciplinary teams with expertise in the many health and contextual factors that must be considered. Recent advances in study design include the use of imaging and biomarkers to assess mechanisms and approaches that raise the ceiling on measurement and integrate assessment of exposures over time. Study implementation requires careful planning and monitoring to maintain fidelity to the scientific goals. Analysis of longitudinal data requires approaches that account for inevitable missing data. New studies should take advantage of the experience obtained from longitudinal studies on aging already conducted.
longitudinal studies; observational studies; study design; data analysis
Background: slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests.
Hypothesis: we hypothesise that slower information processing explains this association, while tests of language or memory will not.
Methods: data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index).
Results: in linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association.
Conclusions: we conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.
prefrontal volume; gait speed; information processing; elderly
To examine the relationships between knee osteoarthritis (OA) and muscle parameters in a biracial cohort of older adults.
858 participants in the Health, Aging and Body Composition Study were included in this cross-sectional analysis. Computed tomography (CT) was used to measure muscle area and quadriceps strength was measured isokinetically. Muscle quality (specific torque) was defined as strength per unit of muscle area for both total thigh and quadriceps. Knee OA was assessed based on radiographic features and knee pain. We compared muscle parameters between those with and without radiographic knee OA (+RKOA, −RKOA) and among four groups defined by +/− RKOA with and without pain.
The mean age was 73.5 (2.9) years and mean BMI was 27.9 (4.8) kg/m2. 58% of participants were women and 44% were Black. Compared to − RKOA, +RKOA participants had a higher BMI (30.2 vs. 26.8 kg/m2), larger thigh muscles (117.9 vs. 108.9 cm2), and a greater amount of intermuscular fat (12.5 vs. 9.9 cm2) (all p<0.0001). In adjusted models, +RKOA subjects had significantly lower specific torque (p<0.001), indicating poorer muscle quality, than −RKOA subjects, but there was no difference between groups in quadriceps specific torque. +RKOA/−pain (p<0.05) and +RKOA/+pain (p<0.001) subjects had lower specific torque compared to −RKOA/−pain group. There were no significant differences in quadriceps specific torque among RKOA/pain groups.
Muscle quality was significantly poorer in participants with RKOA regardless of pain status. Future studies should address how lifestyle interventions might affect muscle quality and progression of knee OA.