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1.  The Demographic and Medical Correlates of Plasma Aβ40 and Aβ42 
Plasma amyloid beta-42 (Aβ42) and Aβ42/Aβ40 are increasingly recognized as biomarkers for dementia, with low levels indicating increased risk. Little is known about the demographic and medical correlates of plasma Aβ40 or Aβ42. In 997 community-dwelling, non-demented older adults from the Health, Aging and Body Composition Study, we determined the cross-sectional association between a wide range of demographic and medical variables with Aβ40 and Aβ42. In multivariate stepwise linear regression models, Aβ40 was significantly associated with race (β=−14.70, F=22.01, p<0.0001), age (β=1.34, F=6.39, p=0.01), creatinine (β=52.91, F=151.77, p<0.0001), and serum brain-derived neurotrophic factor (BDNF) (β=−0.0004, F=7.34, p=0.007); Aβ42 was significantly associated with race (β=−3.72, F=30.83, p<0.0001), sex (β=1.39, F=4.32, p=0.04), education (β=1.50, F=4.78, p=0.03), Apolipoprotein E (APOE) e4 allele status (β=−2.82, F=16.57, p<0.0001), and creatinine (β=9.32, F=120.09, p<0.0001). These correlates should be considered as potential confounders in future studies investigating plasma Aβ as a biomarker of dementia. Understanding fully how these correlates mediate or modify the association between plasma Aβ and dementia will be a fundamental step in determining the biological pathways through which plasma Aβ40 and Aβ42 are associated with dementia, and in determining their full potential as biomarkers.
PMCID: PMC3473156  PMID: 22732677
Plasma amyloid beta; dementia; cognitive decline; biomarker; epidemiology
2.  Modifiable Risk Factors for Pneumonia Requiring Hospitalization among Community-Dwelling Older Adults: The Health, Aging, and Body Composition Study 
Pneumonia requiring hospitalization remains a major public health problem among community-dwelling older adults. Impaired oral hygiene is a modifiable risk factor for healthcare-associated pneumonia, but its role in community-acquired pneumonia is unclear.
To identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization among community-dwelling older adults.
Prospective observational cohort study
Memphis, Tennessee and Pittsburgh, Pennsylvania
Of 3075 well-functioning community-dwelling adults aged 70–79 years enrolled in the Health, Aging, and Body Composition Study from 1997–1998, 1441 had complete data, dental exam within six months of baseline, and were eligible for this study.
The primary outcome was pneumonia requiring hospitalization through 2008.
Of 1441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male gender (HR 2.07, 95%CI 1.51–2.83), white race (HR 1.44, 95%CI 1.03–2.01), history of pneumonia (HR 3.09, 95%CI 1.86–5.14), pack-years of smoking (HR 1.006, 95%CI 1.001–1.011), and percent predicted FEV1 (moderate vs. mild/normal lung function [HR 1.78, 95%CI 1.28–2.48], severe vs. mild/normal lung function [HR 2.90, 95%CI 1.51–5.57]) were non-modifiable risk factors for pneumonia. Incident mobility limitation (HR 1.77, 95%CI 1.32–2.38) and higher mean oral plaque score (HR 1.29, 95%CI 1.02–1.64) were modifiable risk factors for pneumonia. Average Attributable Fractions revealed that 11.5% of pneumonias were attributed to incident mobility limitation and 10.3% to mean oral plaque score ≥1.
Incident mobility limitation and higher mean oral plaque score were two modifiable risk factors attributable for 22% of pneumonias requiring hospitalization. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults.
PMCID: PMC3714374  PMID: 23772872
pneumonia; community-dwelling; risk factors
3.  Association of total and computed tomographic measures of regional adiposity with incident cancer risk: a prospective population-based study of older adults 
Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer and obesity-related cancer (per NCI definition) in participants initially aged 70–79 without prevalent cancer (1,179 men, 1,340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry and computed tomography measures: visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), thigh intermuscular adipose tissue and thigh muscle attenuation (Hounsfield Unit, HU), low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression adjusted for demographics, lifestyle variables and medical conditions. During follow-up 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01–1.30 per SD increase, HR 1.15, 95% CI 1.02–1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03–1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06–1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08–1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women.
PMCID: PMC4071344  PMID: 24869972
Obesity; weight; adipose; body fat; cancer incidence; cancer risk; aging
4.  Patterns of Leisure-Time Physical Activity Participation in a British Birth Cohort at Early Old Age 
PLoS ONE  2014;9(6):e98901.
Using data from a nationally representative British birth cohort we characterized the type and diversity of leisure-time physical activity that 2,188 participants (age 60–64 years) engaged in throughout the year by gender and obesity. Participants most commonly reported walking (71%), swimming (33%), floor exercises (24%) and cycling (15%). Sixty-two percent of participants reported ≥2 activities in the past year and 40% reported diversity on a regular basis. Regular engagement in different types of activity (cardio-respiratory, balance/flexibility and strength) was reported by 67%, 19% and 11% of participants, respectively. We found gender differences, as well as differences by obesity status, in the activities reported, the levels of activity diversity and activity type. Non-obese participants had greater activity diversity, and more often reported activities beneficial for cardio-respiratory health and balance/flexibility than obese participants. These findings may be used to inform the development of trials of physical activity interventions targeting older adults, and those older adults with high body mass index.
PMCID: PMC4049596  PMID: 24911018
5.  Association Between Hypoglycemia and Dementia in a Biracial Cohort of Older Adults With Diabetes Mellitus 
JAMA internal medicine  2013;173(14):1300-1306.
Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia.
To prospectively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM.
Prospective population-based study.
We studied 783 older adults with DM (mean age, 74.0 years; 47.0% of black race/ethnicity; and 47.6% female) who were participating in the prospective population-based Health, Aging, and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher.
Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications. Hypoglycemic events were determined during the follow-up period by hospital records.
During the 12-year follow-up period, 61 participants (7.8%) had a reported hypoglycemic event, and 148 (18.9%) developed dementia. Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4% vs 17.6%, P < .001; multivariate-adjusted hazard ratio, 2.1; 95% CI, 1.0–4.4). Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia (14.2% vs 6.3%, P < .001; multivariate-adjusted hazard ratio, 3.1; 95% CI, 1.5–6.6). Further adjustment for stroke, hypertension, myocardial infarction, and cognitive change scores produced similar results.
Among older adults with DM, there seems to be a bidirectional association between hypoglycemia and dementia.
PMCID: PMC4041621  PMID: 23753199
6.  Candidate Gene Association Study of BMI-Related Loci, Weight, and Adiposity in Old Age 
Most genome-wide association studies are confined to middle-aged populations. It is unclear whether associations between single nucleotide polymorphisms (SNPs) and obesity persist in old age. We aimed to relate 10 body mass index (BMI)–associated SNPs to weight, BMI, % fat, visceral and subcutaneous adipose tissue in Health ABC and AGES-Reykjavik comprising 4,846 individuals of European Ancestry, and 1,139 African Americans over age 65. SNPs were scaled using effect estimates from candidate SNPs. In Health ABC, a SNP near GNPDA2 was modestly associated with weight and SAT area (p = .008, p = .001). Risk score (sum of scaled SNPs) was associated with weight, BMI, and SAT area (p < .0001 for all), but neither GNPDA2 nor risk score was associated with weight, BMI, visceral adippose tissue, subcutaneous adipose tissue, or % fat in AGES-Reykjavik. In African Americans, a SNP near SEC16B was weakly associated with weight (p = .04). In this sample of older adults, no BMI-associated SNPs were associated with weight or adiposity.
PMCID: PMC3660116  PMID: 23160366
Obesity; Aging; Genetics; SNPs.
7.  Partially ordered mixed hidden Markov model for the disablement process of older adults 
At both the individual and societal levels, the health and economic burden of disability in older adults is enormous in developed countries, including the U.S. Recent studies have revealed that the disablement process in older adults often comprises episodic periods of impaired functioning and periods that are relatively free of disability, amid a secular and natural trend of decline in functioning. Rather than an irreversible, progressive event that is analogous to a chronic disease, disability is better conceptualized and mathematically modeled as states that do not necessarily follow a strict linear order of good-to-bad. Statistical tools, including Markov models, which allow bidirectional transition between states, and random effects models, which allow individual-specific rate of secular decline, are pertinent. In this paper, we propose a mixed effects, multivariate, hidden Markov model to handle partially ordered disability states. The model generalizes the continuation ratio model for ordinal data in the generalized linear model literature and provides a formal framework for testing the effects of risk factors and/or an intervention on the transitions between different disability states. Under a generalization of the proportional odds ratio assumption, the proposed model circumvents the problem of a potentially large number of parameters when the number of states and the number of covariates are substantial. We describe a maximum likelihood method for estimating the partially ordered, mixed effects model and show how the model can be applied to a longitudinal data set that consists of N = 2,903 older adults followed for 10 years in the Health Aging and Body Composition Study. We further statistically test the effects of various risk factors upon the probabilities of transition into various severe disability states. The result can be used to inform geriatric and public health science researchers who study the disablement process.
PMCID: PMC3777389  PMID: 24058222
Latent Markov model; continuation ratio model; EM algorithm; generalized linear model; Health ABC study
8.  Mitochondrial DNA sequence associations with dementia and amyloid-β in elderly African Americans 
Neurobiology of aging  2013;35(2):442.e1-442.e8.
Mitochondrial dysfunction occurs early in the course of several neurodegenerative diseases, and is potentially related to increased oxidative damage and amyloid-β (Aβ) formation in Alzheimer’s disease. The goals of this study were to assess mtDNA sequence associations with dementia risk, 10-year cognitive change, and markers of oxidative stress and Aβ among 1089 African-Americans in the population-based Health, Aging, and Body Composition Study. Participants were free of dementia at baseline, and incidence was determined in 187 (18%) cases over 10 to 12 follow-up years. Haplogroup L1 participants were at increased risk for developing dementia (odds ratio = 1.88, 95% confidence interval = 1.23–2.88, p = 0.004), lower plasma Aβ42 levels (p = 0.03), and greater 10-year decline on the Digit Symbol Substitution Test (p = 0.04) when compared with common haplogroup L3. The p.V193I, ND2 substitution was associated with significantly higher Aβ42 levels (p = 0.0012), and this association was present in haplogroup L3 (p = 0.018) but not L1 (p = 0.90) participants. All associations were independent of potential confounders, including APOEε4 status and nuclear genetic ancestry. Identification of mtDNA sequence variation associated with dementia risk and cognitive decline may contribute to the development of new treatment targets and diagnostic tests that identify responders to interventions targeting mitochondria.
PMCID: PMC4019378  PMID: 24140124
Dementia; Mitochondria; mtDNA; Amyloid-β; Oxidative stress
9.  The Role of Metabolic Syndrome, Adiposity, and Inflammation in Physical Performance in the Health ABC Study 
Metabolic syndrome (MetS) and functional limitation have been linked, but whether and how specific components of MetS and associated factors, such as inflammation, drive this relationship is unknown.
Data are from 2,822 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition (Health ABC) study and followed for 5 years. Presence of MetS at baseline was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Interleukin-6, C-reactive protein, and body fat mass were measured at baseline. Measures of physical performance, including 400-m walk time, 20-m walking speed, and the Health ABC physical performance battery (PPB) were obtained at baseline and examination years 2, 4, and 6.
A total of 1,036 (37%) individuals met criteria for MetS. MetS was associated with poorer physical performance at baseline. Effect estimates between MetS and gait speed, and components of the Health ABC PPB (standing balance and repeated sit-to-stand performance) were modestly attenuated after adjustment for inflammation. All associations were attenuated to nonsignificance after adding total body fat mass to the model. Longitudinal analyses yielded similar results. Individual MetS component analysis revealed that abdominal obesity explained the largest fraction of the variation in physical performance.
Although inflammatory biomarkers partially accounted for the relationship between MetS and aspects of physical performance, overall findings implicate adiposity as the primary factor explaining poorer physical performance in older adults with MetS.
PMCID: PMC3623483  PMID: 23109678
Metabolic syndrome; Physical function; Inflammation; Obesity.
10.  Mitochondrial DNA variation in human metabolic rate and energy expenditure 
Mitochondrion  2011;11(6):855-861.
The role of climate in driving selection of mtDNA as Homo sapiens migrated out of Africa into Eurasia remains controversial. We evaluated the role of mtDNA variation in resting metabolic rate (RMR) and total energy expenditure (TEE) among 294 older, community-dwelling African and European American adults from the Health, Aging and Body Composition Study. Common African haplogroups L0, L2 and L3 had significantly lower RMRs than European haplogroups H, JT and UK with haplogroup L1 RMR being intermediate to these groups. This study links mitochondrial haplogroups with ancestry-associated differences in metabolic rate and energy expenditure.
PMCID: PMC3998521  PMID: 21586348
Metabolic rate; Energetics; Mitochondria; Mitochondrial haplogroups; mtDNA; Oxidative phosphorylation
11.  Genetic Variation at NCAN Locus is Associated with Inflammation and Fibrosis in Non-alcoholic Fatty Liver Disease in Morbid Obesity 
Human heredity  2013;75(1):10.1159/000346195.
Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity.
In 1,092 bariatric patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed.
We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. Rs2228603[T] was associated with lower serum LDL, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD.
NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.
PMCID: PMC3864002  PMID: 23594525
Obesity; dyslipidemia; steatohepatitis; cirrhosis; steatosis
12.  Trajectories of Gait Speed Predict Mortality in Well-Functioning Older Adults: The Health, Aging and Body Composition Study 
Although gait speed slows with age, the rate of slowing varies greatly. To date, little is known about the trajectories of gait speed, their correlates, and their risk for mortality in older adults.
Gait speed during a 20-m walk was measured for a period of 8 years in initially well-functioning men and women aged 70–79 years participating in the Health, Aging and Body Composition study. We described the trajectories of gait speed and examined their correlates using a group-based mixture model. Also risk associated with different gait speed trajectories on all-cause mortality was estimated using a Cox-proportional hazard model.
Of 2,364 participants (mean age, 73.5±2.9 years; 52% women), we identified three gait speed trajectories: slow (n = 637), moderate (n = 1,209), and fast decline (n = 518). Those with fast decline slowed 0.030 m/s per year or 2.4% per year from baseline to the last follow-up visit. Women, blacks, and participants who were obese, had limited knee extensor strength, and had low physical activity were more likely to have fast decline than their counterparts. Participants with fast decline in gait speed had a 90% greater risk of mortality than those with slow decline.
Despite being well-functioning at baseline, a quarter of older adults experienced fast decline in gait speed, which was associated with an increased risk of mortality.
PMCID: PMC3593620  PMID: 23051974
Gait speed; Older adults; Mortality.
13.  An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia 
Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia.
The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed.
The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%).
The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment.
PMCID: PMC3991139  PMID: 24737561
Muscle; Sarcopenia; Lean mass.
14.  Criteria for Clinically Relevant Weakness and Low Lean Mass and Their Longitudinal Association With Incident Mobility Impairment and Mortality: The Foundation for the National Institutes of Health (FNIH) Sarcopenia Project 
This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed ≤ 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation.
Among 4,411 men and 1,869 women pooled from 6 cohort studies, 3-year likelihood for incident mobility impairment and mortality over 10 years were determined for individuals with weakness, low lean mass, and for those having both. Weakness was defined as low grip strength (<26kg men and <16kg women) and low grip strength-to-body mass index (BMI; kg/m2) ratio (<1.00 men and <0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was categorized as low appendicular lean mass (ALM; <19.75kg men and <15.02kg women) and low ALM-to-BMI ratio (<0.789 men and <0.512 women).
Low grip strength (men: odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.34–3.99; women: OR = 1.99, 95% CI 1.23–3.21), low grip strength-to-BMI ratio (men: OR = 3.28, 95% CI 1.92–5.59; women: OR = 2.54, 95% CI 1.10–5.83) and low ALM-to-BMI ratio (men: OR = 1.58, 95% CI 1.12–2.25; women: OR = 1.81, 95% CI 1.14–2.87), but not low ALM, were associated with increased likelihood for incident mobility impairment. Weakness increased likelihood of mobility impairment regardless of low lean mass. Mortality risk patterns were inconsistent.
These findings support our cut-points for low grip strength and low ALM-to-BMI ratio as candidate criteria for clinically relevant weakness and low lean mass. Further validation in other populations and for alternate relevant outcomes is needed.
PMCID: PMC3991140  PMID: 24737560
Muscle; Sarcopenia; Mobility; Impairment.
15.  Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness 
Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women).
In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness.
In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]).
ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness.
PMCID: PMC3991141  PMID: 24737559
Muscle; Sarcopenia; Cutpoints.
16.  The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates 
Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts.
The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups.
The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women.
These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.
PMCID: PMC3991146  PMID: 24737557
Aging; Sarcopenia; Muscle; Outcomes; Weakness.
17.  Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness 
Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s.
In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment.
In men, a grip strength of 26–32 kg was classified as “intermediate” and less than 26 kg as “weak”; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01–4.38) and 7.62 (95% CI 6.13–9.49), respectively. In women, a grip strength of 16–20 kg was classified as “intermediate” and less than 16 kg as “weak”; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20–2.71) and 4.42 (95% CI 3.94–4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure.
Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function.
PMCID: PMC3991145  PMID: 24737558
Muscle; Sarcopenia; Grip strength; Physical function; Gait speed.
18.  Reproducibility of peroneal motor nerve conduction measurement in older adults 
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.
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.
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.
NC measures have moderate to high intraobsever reproducibility in older adults and are not affected by diabetes, race, or gender.
These data provide evidence to support use of these measures in aging research.
PMCID: PMC3562564  PMID: 23022036
Motor nerve conduction; aging; peripheral nerve function; reproducibility; diabetes
19.  Objective measurements of daily physical activity patterns and sedentary behaviour in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study 
Age and Ageing  2012;42(2):222-229.
Background: objectively measured population physical activity (PA) data from older persons is lacking. The aim of this study was to describe free-living PA patterns and sedentary behaviours in Icelandic older men and women using accelerometer.
Methods: from April 2009 to June 2010, 579 AGESII-study participants aged 73–98 years wore an accelerometer (Actigraph GT3X) at the right hip for one complete week in the free-living settings.
Results: in all subjects, sedentary time was the largest component of the total wear time, 75%, followed by low-light PA, 21%. Moderate-vigorous PA (MVPA) was <1%. Men had slightly higher average total PA (counts × day−1) than women. The women spent more time in low-light PA but less time in sedentary PA and MVPA compared with men (P < 0.001). In persons <75 years of age, 60% of men and 34% of women had at least one bout ≥10 min of MVPA, which decreased with age, with only 25% of men and 9% of women 85 years and older reaching this.
Conclusion: sedentary time is high in this Icelandic cohort, which has high life-expectancy and is living north of 60° northern latitude.
PMCID: PMC3575120  PMID: 23117467
physical activity; accelerometry; sedentary behaviour; older adults; BMI; AGES-Reykjavik; older people
Archives of internal medicine  2011;171(14):1251-1257.
Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on subjective self-reports of physical activity, which only moderately correlate to objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment.
We calculated AEE as 90% of total energy expenditure (assessed over two weeks using doubly-labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998–2000). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination (3MS). Cognitive impairment was defined as a decline of >1.0 SD (9 points) between baseline and follow-up.
After adjustment for baseline 3MS, demographics, fat free mass, sleep duration, self-reported health, and diabetes, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (OR, 95% CI 0.09, 0.01–0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (p-for-trend over tertiles=0.05).
These findings indicate that greater activity energy expenditure may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined.
PMCID: PMC3923462  PMID: 21771893
21.  Low 25-Hydroxyvitamin D Predicts the Onset of Mobility Limitation and Disability in Community-Dwelling Older Adults: The Health ABC Study 
Although low 25-hydroxyvitamin D (25(OH)D) is prevalent among older adults and is associated with poor physical function, longitudinal studies examining vitamin D status and physical function are lacking. We examined the association between 25(OH)D, parathyroid hormone (PTH), and the onset of mobility limitation and disability over 6 years of follow-up in community-dwelling, initially well-functioning older adults participating in the Health, Aging and Body Composition study (n = 2,099).
Serum 25(OH)D and PTH were measured at the 12-month follow-up visit (1998–1999). Mobility limitation and disability (any/severe difficulty walking 1/4 mile or climbing 10 steps) was assessed semiannually over 6 years of follow-up. The association between 25(OH)D, PTH, and mobility limitation and disability was examined using Cox proportional hazard regression models adjusted for demographics, season, behavioral characteristics, and chronic conditions.
At baseline, 28.9% of the participants had 25(OH)D <50 nmol/L and 36.1% had 25(OH)D of 50 to <75 nmol/L. Participants with 25(OH)D <50 and 50 to <75 nmol/L were at greater risk of developing mobility limitation (HR (95% CI): 1.29 (1.04–1.61) and 1.27 (1.05–1.53), respectively) and mobility disability (HR (95% CI): 1.93 (1.32–2.81) and 1.30 (0.92–1.83), respectively) over 6 years of follow-up compared with participants with 25(OH)D ≥75 nmol/L. Elevated PTH, however, was not significantly associated with developing mobility limitation or disability.
Low 25(OH)D was associated with an increased risk of mobility limitation and disability in community-dwelling, initially well-functioning black and white older adults. Prevention or treatment of low 25(OH)D may provide a pathway for reducing the burden of mobility disability in older adults.
PMCID: PMC3598356  PMID: 22573914
25-hydroxyvitamin D; Mobility limitation; Vitamin D; Parathyroid hormone
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.
PMCID: PMC3521843  PMID: 23172923
pulse wave velocity; small vessel disease; longitudinal; fractional anisotropy; community-dwelling elderly
23.  Educational Attainment and Late Life Telomere Length in the Health, Aging and Body Composition Study 
Brain, behavior, and immunity  2012;27(1):15-21.
Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2,599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B=125, SE= 47.6, p = .009). A significant interaction of race and education (B = 207.8, SE = 98.7, p = .035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = .012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks.
PMCID: PMC3543785  PMID: 22981835
Socioeconomic status; education; telomere length; race; health disparities
24.  Pulmonary Function Impairment May be An Early Risk Factor for Late-Life Cognitive Impairment 
Low pulmonary function (PF) is associated with poor cognitive function and dementia. There are few studies of change in PF in mid-life and late-life cognitive status.
Design and Participants
We studied this is 3,665 subjects from AGES-Reykjavik Study who had at least one measure of forced expiratory volume/ 1 sec (FEV1) and were cognitively tested on average 23 years later. A subset of 1,281 subjects had two or three measures of FEV1 acquired over a 7.8 year period. PF was estimated as FEV1/Height2. Rate of PF decline was estimated as the slope of decline over time. Cognitive status was measured with continuous scores of memory, speed of processing, and executive function, and as the dichotomous outcomes of mild cognitive impairment (MCI) and dementia.
Lower PF measured in mid-life predicted lower memory, speed of processing, executive function, and higher likelihood of MCI and dementia 23 years later. Decrease of PF over a 7.8-year period in mid-life was not associated with lower cognitive function or dementia.
Reduced PF measured in mid-life may be an early marker of later cognitive problems. Additional studies characterizing early and late PF changes are needed.
PMCID: PMC3545414  PMID: 23311554
Cognition; Dementia; Forced Expiratory Volume; Longitudinal Cohort Studies
25.  Hyperleptinemia, Adiposity, and Risk of Metabolic Syndrome in Older Adults 
Background. Abdominal adiposity and serum leptin increase with age as does risk of metabolic syndrome. This study investigates the prospective association between leptin and metabolic syndrome risk in relation to adiposity and cytokines. Methods. The Health, Aging, and Body Composition study is a prospective cohort of older adults aged 70 to 79 years. Baseline measurements included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous fat. Multivariate logistic regression was used to determine the association between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after 6 years of follow-up among 1,120 men and women. Results. Leptin predicted metabolic syndrome in men (P for trend = 0.0002) and women (P for trend = 0.0001). In women, risk of metabolic syndrome increased with higher levels of leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile 3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential confounders. Leptin remained independently associated with metabolic syndrome risk after additional adjustment for adiposity, cytokines, and CRP. Among men, this association was no longer significant after controlling for adiposity. Conclusion. Among older women, elevated concentrations of leptin may increase the risk of metabolic syndrome independent of adiposity and cytokines.
PMCID: PMC3888758  PMID: 24455217

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