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Background: the 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes.Methods: white men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength Results: mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2: 0.0%]; SDOC [2.75 (2.28, 3.31), I2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2: 58.3%].Conclusions: there was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.

Supplemental material, sj-docx-1-hpp-10.1177_15248399231162377 for Program Factors Affecting Weight Loss and Mobility in Older Adults: Evidence From the Mobility and Vitality Lifestyle Program (MOVE UP) by Xinran Liu, Lori A. Kieffer, Jennifer King, Brandi Boak, Janice C. Zgibor, Kenneth J. Smith, Lora E. Burke, John M. Jakicic, Linda N. Semler, Michelle E. Danielson, Anne B. Newman, Elizabeth M. Venditti and Steven M. Albert in Health Promotion Practice

Additional file 1: Supplementary Table S1. Drug list of fall risk increasing drugs. Supplementary Table S2. Adjusted hazard ratios of persistent polypharmacy and FRID on fall injury in the sensitivity analyses. Supplementary Table S3. Adjusted hazard ratios for persistent polypharmacy with varied cut points for medication counts and fall injury risk.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL≥100mg/dl (compared with&nbsp

BackgroundLean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.ObjectivesTo determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.MethodsWe performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n=38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).ResultsSeven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.ConclusionsIn conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Background:Animal studies suggest that acidosis protects against arterial calcification, which contributes to arterial stiffness. The goal of this study was to investigate the associations of serum bicarbonate and pH with arterial stiffness in community-living older adults. Methods:We performed cross-sectional analyses among 1698 well-functioning participants 70-79 years of age. Bicarbonate and pH were measured by arterialized venous blood gas at the point of care. Bicarbonate was categorized into low (7.40-7.42 and >7.42. Arterial stiffness was evaluated by pulse wave velocity (PWV) and high ankle-brachial index (ABI; >1.3/incompressible). We used linear and logistic regression to evaluate the association of bicarbonate and AVpH with PWV and high ABI, respectively. Results:The mean age was 76 years and 15% had an estimated glomerular filtration rate (eGFR)

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

BackgroundThe relationship between sleep disruption, independent of obstructive sleep apnea (OSA), and atrial fibrillation (AF) is unknown.ObjectiveThe purpose of this study was to determine whether poor sleep itself is a risk factor for AF.MethodsWe first performed an analysis of participants in the Health eHeart Study and validated those findings in the longitudinal Cardiovascular Health Study, including a subset of patients undergoing polysomnography. To determine whether the observed relationships readily translated to medical practice, we examined 2005-2009 data from the California Healthcare Cost and Utilization Project.ResultsAmong 4553 Health eHeart participants, the 526 with AF exhibited more frequent nighttime awakening (odd ratio [OR] 1.47; 95% confidence interval [CI] 1.14-1.89; P = .003). In 5703 Cardiovascular Health Study participants followed for a median 11.6 years, frequent nighttime awakening predicted a 33% greater risk of AF (hazard ratio [HR] 1.33; 95% CI 1.17-1.51; P

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30minutes spent performing activities ≥500counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24months), both the number of steps per day (per 500steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500counts per minute (per 30minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

BackgroundMusculoskeletal pain is highly prevalent and limits mobility in older adults. A potential mechanism by which pain affects mobility could be through its negative impact on the brain. We examined whether structural integrity of cerebral gray and white matter (WM) mediated the relationship between pain and mobility in community-dwelling older adults.MethodsMusculoskeletal pain, gait speed, and neuroimaging data were obtained concurrently from the Health ABC study (mean age = 83/56% female, n = 212). Microstructural gray matter integrity was measured by mean diffusivity (MD), WM microstructure and macrostructure were measured by fractional anisotropy (FA) and WM hyperintensities (WMH), respectively. Regression models were adjusted for gray matter atrophy, age, gender, medication use, and obesity. Bootstrapped mediation methods were used (1,000 bootstrapped samples, 95% confidence intervals).ResultsThe associations of musculoskeletal pain with WMH (β = .19, p < .05) and FA (β = -.18, p < .05) were robust to adjustment for gender, medication use, age, body mass index (BMI), and brain atrophy. Participants who experienced both knee and back pain had a significantly slower gait speed (~0.11 m/s) than those without knee or back pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA significantly mediated the pain-gait speed relationship. Associations between pain and MD were not significant, and MD did not modify the association between pain and gait speed.ConclusionsCerebral WM integrity may contribute to the detrimental effects of musculoskeletal pain on mobility, although pre-existing WM integrity may also simultaneously amplify pain and decrease mobility. Future studies are needed to further understand whether successful pain management may significantly improve both brain health and mobility.

BackgroundMobility limitation is highly prevalent among older adults and is central to the loss of functional independence. Dynamic isokinetic muscle fatigue testing may reveal increased vulnerability to disability and mortality beyond strength testing.MethodsWe studied community-dwelling older adults enrolled in the Health Aging and Body Composition study (age range: 71-82) free of mobility disability and who underwent isokinetic muscle fatigue testing in 1999-2000 (n = 1,963). Isokinetic quadriceps work and fatigue index was determined over 30 repetitions and compared with isometric quadriceps maximum torque. Work was normalized to leg lean mass accounting for gender-specific differences (specific work). The primary outcome was incident persistent severe lower extremity limitation (PSLL), defined as two consecutive reports of either having a lot of difficulty or being unable to walk 1/4 mile or climb 10 steps without resting. The secondary outcome was all-cause mortality.ResultsThere were 608 (31%) occurrences of incident PSLL and 488 (25%) deaths during median follow-up of 9.3 years. After adjustment, lower isokinetic work was associated with significantly greater risks of PSLL and mortality across the full measured range. Hazard ratios per standard deviation lower specific isokinetic work were 1.22 (95% CI 1.12, 1.33) for PSLL and 1.21 (95% CI 1.13, 1.30) for mortality, respectively. Lower isometric strength was associated with PSLL, but not mortality. Fatigue index was not associated with PSLL or mortality.ConclusionsMuscle endurance, estimated by isokinetic work, is an indicator of muscle health associated with mobility limitation and mortality providing important insight beyond strength testing.

BackgroundPrior studies have only considered one measurement of physical performance in its relationship to fractures and mortality. A single measurement is susceptible to large within-person changes over time, and thus, may not capture the true association between physical performance and the outcomes of interest.MethodsUsing data from the Study of Osteoporotic Fractures, we followed 7,015 women enrolled prior to age 80 years who had outcome information beyond this age. Trajectories of walking speed (m/s) and chair stand speed (stands/s) were estimated up to the last visit prior to age 80 years using mixed-effects linear regression. Physical performance at age 80 (PF_age80) was assessed at the last visit prior to age 80 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression and multivariate models adjusted for all other covariates.ResultsGreatest walking speed decline and chair stand speed decline were both associated with higher risk of hip fracture (HR: 1.28; 95% CI: 1.03, 1.58 and HR: 1.26; 95% CI: 1.03, 1.54, respectively), but not nonspine fractures. Greatest walking speed decline and chair stand speed decline were both associated with a significant 29% (95% CI: 17-42%) and 27% (95% CI: 15-39%) increased risk of mortality, respectively.ConclusionsGreatest declines in walking speed and chair stand speed were both associated with an increased risk of hip fracture and mortality independent of PF_age80 and other important confounders. Both physical performance change and the single physical performance measurement should be considered in the etiology of hip fracture and mortality.

BackgroundFew cohort studies have examined longitudinal associations between age-related changes in cognition and physical performance. Further, whether these associations differ for men versus women or can be attributed to differences in physical activity (PA) is unknown.MethodsParticipants were 2,876 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 52% female; 39% black) studied over a 9-year period. Usual gait speed, self-reported PA, and two cognitive measures-Digit Symbol Substitution Test (DSST) and Mini-Modified Mental State examination (3MS)-were assessed years 0 (ie, baseline), 4, and 9.ResultsEarly decline between years 0 and 4 in gait speed predicted later decline between years 4 and 9 in performance on the 3MS (β = 0.10, p = .004) and on the DSST (β = 0.16, p < .001). In contrast, the associations between early decline in cognition and later decline in gait speed were weaker and were non-significant after correcting for multiple comparisons (β = 0.08, p = .019 for 3MS and β = .06, p = .051 for DSST). All associations were similar for women and men and were unaltered when accounting for PA levels.ConclusionsThe results indicate declining gait speed as a precursor to declining cognitive functioning, and suggest a weaker reciprocal process among older women and men.

BackgroundThe present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.MethodsParticipants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ≥1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.ResultsOver a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.ConclusionsIn this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes.

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7years of follow-up. Men answered questionnaires about fractures every 4months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment.

ObjectivesTo determine whether lifestyle factors, measured late in life, could compress the disabled period toward the end of life.DesignCommunity-based cohort study of older adults followed from 1989 to 2015.SettingFour U.S. communities.ParticipantsCommunity-living men and women aged 65 and older (N = 5,248, mean age 72.7 ± 5.5, 57% female, 15.2% minority) who were not wheelchair dependent and were able to give informed consent at baseline.MeasurementsMultiple lifestyle factors, including smoking, alcohol consumption, physical activity, diet, body mass index (BMI), social networks, and social support, were measured at baseline. Activities of daily living (ADLs) were assessed at baseline and throughout follow-up. Years of life (YoL) was defined as years until death. Years of able life (YAL) was defined as years without any ADL difficulty. YAL/YoL%, the proportion of life lived able, was used to indicate the relative compression or expansion of the disabled period.ResultsThe average duration of disabled years was 4.5 (out of 15.4 mean YoL) for women and 2.9 (out of 12.4 mean YoL) for men. In a multivariable model, obesity was associated with 7.3 percentage points (95% confidence interval (CI) = 5.4-9.2) lower YAL/YoL% than normal weight. Scores in the lowest quintile of the Alternate Healthy Eating Index were associated with a 3.7% (95% CI = 1.6-5.9) lower YAL/YoL% than scores in the highest quintile. Every 25 blocks walked in a week was associated with 0.5 percentage points (95% CI = 0.3-0.8) higher YAL/YoL%.ConclusionThe effects of healthy lifestyle factors on the proportion of future life lived free of disability indicate that the disabled period can be compressed, given the right combination of these factors.

BackgroundWhite matter hyperintensities (WMH), a common marker of cerebral small vessel disease, and lower microstructural integrity of normal-appearing white matter are associated with slower gait. How these cerebral measures interact in relation to slower gait is unknown. We assessed whether microstructural integrity of normal-appearing white matter, measured by fractional anisotropy (FA), moderates the association of higher WMH with slower gait.MethodsWMH, FA, and gait speed were acquired for 265 community-dwelling older adults (average age = 82.9 years).ResultsThe inverse association between WMH and gait was robust to adjustment for age, gender, muscle strength, obesity, stroke, and hypertension (fully adjusted model: βs = -0.19, p = .001). The interaction between WMH and FA was significant; analyses stratified by FA showed that the inverse association between WMH and gait speed was significant only for those with low FA (FA < median, fully adjusted model: βs = -0.28, p = .001). Voxel-based results were similar for participants with FA less than median, there was an inverse association between gait speed and WMH which extended throughout the white matter (genu and body of corpus callosum, anterior limb of internal capsule, corona radiata, and superior longitudinal and fronto-occipital fasciculus). In contrast, for participants with FA ≥ median, the association was limited to the genu of corpus callosum, the cingulum, and the inferior longitudinal fasciculus.ConclusionsMicrostructural integrity is a moderating factor in the association between WMH and gait. Future studies should examine whether higher microstructural integrity represents a source of compensation in those with greater WMH burden to maintain function in late life.

ObjectivesTo ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity).DesignProspective, community-based cohort study in four U.S. cities.SettingCardiovascular Health Study.ParticipantsIndividuals aged 65 and older.MeasurementsParticipants were categorized into three groups according to extent of disease (assessed noninvasively), vigor, and frailty (expected agers (n=3,528, extent of disease similar to vigor and frailty-reference group), adapters (n=882, higher disease but vigorous), and prematurely frail (n=855, lower disease but frail)) and compared according to years of able life (YAL), years of self-reported healthy life (YHL), and mortality using multivariable regression and survival analysis.ResultsAfter adjustment, adapters had 0.97 (95% confidence interval (CI)=0.60-1.33) more YAL and 0.54 (95% CI=0.19-0.90) more YHL than expected agers, and those who were prematurely frail had -0.99 (95% CI=-1.36 to -0.62) fewer YAL and -0.53 (95% CI=-0.89 to -0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers (P&nbsp

ObjectiveAlthough prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).Approach and resultsAmong Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI 0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50).ConclusionsHigher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

BackgroundDepression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality.MethodsResponses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates.ResultsThree trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk.ConclusionsTrajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care.

BackgroundDespite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time.MethodsHealth, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (≥2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long- versus short-term (≥2 vs

BackgroundMitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease.MethodsWe examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study.ResultsElevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007).ConclusionsThese results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments.

BackgroundMitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study.MethodsWe investigated the role of common mitochondrial DNA variation (n = 1,580) and complete mitochondrial DNA sequences (n = 138) on peroneal motor nerve conduction velocity and amplitude, average vibration detection threshold, and monofilament sensitivity.ResultsNominal associations among common mitochondrial DNA variants and haplogroups were identified but were not statistically significant after adjustment for multiple comparisons. Sequence-based approaches were used to identify aggregate variant associations across the 16S rRNA (weighted-sum, p = 2E-05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of these rare 16S variants occurred at or near sites with earlier disease associations and are also in close proximity to the peptidyl transferase center, which is the catalytic center of the 16S rRNA CONCLUSIONS: These results suggest that sequence variation related to mitochondrial protein synthesis/assembly is associated with peripheral nerve function and may provide insight into targets for intervention or new clinical strategies to preserve nerve function in late life.

IntroductionWe examined whether statins are associated with better cerebral white (WM) and gray matter (GM) indices in community-dwelling elders.MethodsIn 295 older adults, we compared white matter hyperintensities (WMH) on brain magnetic resonance imaging and, total WM fractional anisotropy (FA) and GM mean diffusivity (MD) on diffusion tensor imaging, of Alzheimer's disease (AD) relevant regions in statin-exposed and statin-unexposed participants stratified by Modified Mini-Mental Status Examination (3MS) score.ResultsThere was no overall effect of statin exposure on cerebral structural indices. The interaction between statin exposure and 3MS was significant for total-WMH and WM FA (both P < .05) but not GM MD. In the lowest 3MS tertile (mean: 86), statin-exposed individuals had lower total-WMH and higher WM FA (P = .005 and P = .044) and FA of tracts linked to clinical AD (P-value range= .005-.04) despite statistical adjustments. These differences were not significant in the two higher 3MS tertiles.DiscussionStatins may benefit WM in older adults vulnerable to dementia.

UnlabelledObesity is a well-recognized risk factor for atrial fibrillation (AF), yet adiposity measures other than body mass index (BMI) have had limited assessment in relation to AF risk. We examined the associations of adiposity measures with AF in a biracial cohort of older adults. Given established racial differences in obesity and AF, we assessed for differences by black and white race in relating adiposity and AF.MethodsWe analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates.ResultsIn multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF.ConclusionBody mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.

ObjectivesTo examine body mass index (BMI) trajectories with change in lean mass and physical function in old age.DesignProspective cohort study.SettingHealth, Aging and Body Composition Study.ParticipantsBlack and white men (n = 482) and women (n = 516) aged 73.1 ± 2.7 and initially free of disability.MeasurementsA group-based trajectory model was used to determine BMI trajectories, the path a person's BMI followed over 9 years. Lean mass, gait speed, grip strength, and knee extension strength were assessed at baseline and after 9 years, and relative changes were calculated. Multivariable linear regression was used to determine associations between trajectories and relative change in lean mass and physical function.ResultsFour BMI trajectories were identified for men and four for women. Although all demonstrated a decline in BMI, the rate of decline differed according to trajectory for women only. Men in Trajectory 4 (mean BMI at baseline 33.9 ± 2.3 kg/m(2) ) declined more than those in Trajectory 1 (mean BMI at baseline 22.9 ± 1.6 kg/m(2) ) in gait speed (-9.91%, 95% confidence interval (CI) = -15.15% to -4.67%) and leg strength (-8.63%, 95% CI = -15.62% to -1.64%). Women in Trajectory 4 (mean BMI at baseline 34.9 ± 3.0 kg/m(2) ) had greater losses than those in Trajectory 1 (mean BMI at baseline 20.5 ± 1.6 kg/m(2) ) in lean mass in the arms (-3.19%, 95% CI = -6.16% to -0.23%). No other associations were observed.ConclusionObese men had the highest risk of decline in physical function despite similar weight loss between trajectories, whereas overweight and obese women who lost the most weight had the greatest risk of lean mass loss. The weight at which a person enters old age is informative for predicting loss in lean mass and physical function, illustrating the importance of monitoring weight.

ObjectivesTo determine the association between hearing impairment (HI) and risk and duration of hospitalization in community-dwelling older adults in the United States.DesignProspective observational study.SettingHealth, Aging and Body Composition Study.ParticipantsWell-functioning community-dwelling white and black Medicare beneficiaries aged 70 to 79 at study enrollment in 1997-98 were followed for a median of 12 years.MeasurementsIncidence, annual rate, and duration of hospitalization were the primary outcomes. Hearing was defined as the pure-tone average (PTA) of hearing thresholds in decibels re: hearing level (dB HL) at octave frequencies from 0.5 to 4.0 kHz. Mild HI was defined as a PTA from 25 to 40 dB HL, and moderate or greater HI was defined as a PTA greater than 40 dB HL.ResultsOf the 2,148 participants included in the analysis, 1,801 (83.5%) experienced one or more hospitalizations, with 7,007 adjudicated hospitalization events occurring during the study period. Eight hundred eighty-two (41.1%) participants had normal hearing, 818 (38.1%) had mild HI, and 448 (20.9%) had moderate or greater HI. After adjusting for demographic characteristics and cardiovascular comorbidities, persons with mild HI experienced a 16% (hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.04-1.29) greater risk of incident hospitalization and a 17% (incidence rate ratio (IRR) = 1.17, 95% CI = 1.04-1.32) greater annual rate of hospitalization, and those with moderate or greater HI experienced a 21% (HR = 1.21, 95% CI = 1.06-1.38) greater risk of incident hospitalization and a 19% (IRR = 1.19, 95% CI = 1.04-1.38) greater annual rate of hospitalization than persons with normal hearing. There was no significant association between HI and mean duration of hospitalization.ConclusionHearing-impaired older adults experience a greater incidence and annual rate of hospitalization than those with normal hearing. Investigating whether rehabilitative therapies could affect the risk of hospitalization in older adults requires further study.

The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age = 87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean ± SD/day: 1766 ± 1345 steps, 202 ± 311 kcal, 211 ± 39 min, 1.8 ± 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.

BackgroundPhysical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults.MethodsThe Health, Aging, and Body Composition study is a prospective cohort of 3075 well-functioning older adults. PA and television watching was measured by self-report, and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR 3 ml/min/1.73 m(2). Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function.ResultsIndividuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI, 1.09-1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI, 1.05-1.52) compared with individuals who watched television

BackgroundSlowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals.MethodsData from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models.ResultsThose with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, -0.006).ConclusionsGreater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.

ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults.DesignLongitudinal cohort study.SettingHealth, Aging and Body Composition (Health ABC) Study.ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03.MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1 m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care.ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1 m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1 m/s or more (adjusted odds ratio (AOR) = 0.90, 95% confidence interval (CI) = 0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR = 0.78, 95% CI = 0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up.ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults.

A positive association between cardiorespiratory fitness (CRF) and white matter integrity has been consistently reported in older adults. However, it is unknown whether this association exists in adults over 80 with a range of chronic disease conditions and low physical activity participation, which can influence both CRF and brain health. This study examined whether higher CRF was associated with greater microstructural integrity of gray and white matter in areas related to memory and information processing in adults over 80 and examined moderating effects of chronic diseases and physical activity. CRF was measured as time to walk 400 m as quickly as possible with concurrent 3T diffusion tensor imaging in 164 participants (57.1% female, 40.3% black). Fractional anisotropy (FA) was computed for cingulum, uncinate and superior longitudinal fasciculi. Mean diffusivity (MD) was computed for dorsolateral prefrontal cortex, hippocampus, parahippocampus, and entorhinal cortex. Moderating effects were tested using hierarchical regression models. Higher CRF was associated with higher FA in cingulum and lower MD in hippocampus and entorhinal cortex (β, sex-adjusted p: -0.182, 0.019; 0.165, 0.035; and 0.220, 0.006, respectively). Hypertension attenuated the association with MD in entorhinal cortex. Moderating effects of chronic diseases and physical activity in walking and climbing stairs on these associations were not significant. The association of higher CRF with greater microstructural integrity in selected subcortical areas appears robust, even among very old adults with a range of chronic diseases. Intervention studies should investigate whether increasing CRF can preserve memory and information processing by improving microstructure and potential effects of hypertension management.

In older adults, depressive symptoms are associated with lower quality of life, high morbidity and mortality. This study aims to identify brain magnetic resonance imaging (MRI) features associated with late-life depressive symptoms in the population. Older community-dwelling adults (n=314) from the Health ABC study underwent brain MRI. Logistic regression was used to characterize the relationships between depressive symptoms (Center for Epidemiologic Studies of Depression scale, CES-D) and the following whole-brain variables: white matter hyperintensity (WMH) burden, fractional anisotropy (FA), and gray matter volume (GMV). Analyses examining possible regional differences between the CES-D groups controlled for Modified Mini-Mental State Examination score and diabetes status. The relative importance of localization of the markers was examined by comparing the distribution of significant peaks across the brain. Each whole-brain variable showed loss of integrity associated with high CES-D. For GMV, the odds ratio (OR)=0.84 (95% confidence interval (CI) 0.74, 0.96); for FA, OR=0.714 (95% CI 0.57, 0.88); for WMH, OR=1.89 (95%CI 1.33, 2.69). Voxel-wise analyses and patterns of peak significance showed non-specific patterns for white matter measures. Loss of GMV was most significant in the bilateral insula and anterior cingulate cortex. This study supports a cerebrovascular pattern for depressive symptoms in older adults. The localization of gray matter changes to the insula, a watershed area and a hub of affective circuits, suggests an etiological pathway from ischemia to increased depressive burden.

BackgroundAlthough the beneficial effects of physical activity (PA) on memory and executive function are well established in older adults, little is known about the relationship between PA and brain microstructure and the contributions of physical functional limitations and chronic diseases. This study examined whether higher PA would be longitudinally associated with greater microstructural integrity in memory- and executive function-related networks and whether these associations would be independent of physical function and chronic diseases.MethodsDiffusion tensor imaging was obtained in 2006-2008 in 276 participants (mean age = 83.0 years, 58.7% female, 41.3% black) with PA (sedentary, lifestyle active, and exercise active) measured in 1997-1998. Gait speed, cognition, depressive symptoms, cardiovascular and pulmonary diseases, hypertension, stroke, and diabetes were measured at both time points. Mean diffusivity and fractional anisotropy were computed from normal-appearing gray and white matter in frontoparietal and subcortical networks. Moderating effects of physical function and chronic diseases were tested using hierarchical regression models.ResultsCompared with the sedentary, the exercise active group had lower mean diffusivity in the medial temporal lobe and the cingulate cortex (β, p values: -.405, .023 and -.497, .006, respectively), independent of age, sex, and race. Associations remained independent of other variables, although they were attenuated after adjustment for diabetes. Associations between PA and other neuroimaging markers were not significant.ConclusionsBeing exercise active predicts greater memory-related microstructural integrity in older adults. Future studies in older adults with diabetes are warranted to examine the neuroprotective effect of PA in these networks.

BackgroundIn populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown.Study designLongitudinal observational cohort study.Setting & participantsWell-functioning community-living elders aged 70-79 years at inception.PredictorSerum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer.OutcomesChange in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year.MeasurementsLinear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2).ResultsAt baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations.LimitationsOnly 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population.ConclusionsLower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development.

ObjectivesTo examine whether older adults taking nonsteroidal anti-inflammatory drugs (NSAIDs) decreased the underuse of gastroprotective agents over time.DesignBefore-and-after study.SettingHealth, Aging and Body Composition Study.ParticipantsDaily users of a NSAID (prescription and over the counter (OTC)) at visits in 2002-03 (preperiod; n = 404) and 2006-07 (postperiod; n = 172). The sample had a mean ± standard deviation age of 78.2 ± 2.7 at the preperiod visit and 81.9 ± 2.7 at the postperiod visit. The majority were white and female and had 12 or more years of education.MeasurementsUnderusers were defined as persons taking nonselective NSAIDs who were at risk of peptic ulcer disease (PUD; because of current warfarin or glucocorticoid use or history of PUD) and not using a proton pump inhibitor (PPI) or persons taking cyclooxygenase 2 (COX-2) selective NSAIDs and aspirin who were at risk of PUD (having at least one risk factor) and not using a PPI.ResultsDaily NSAID use decreased from 17.6% to 11.3% (P < .001), and gastroprotective agent underuse decreased from 23.5% to 15.1% (P = .008). Controlling for important covariates, having prescription insurance was somewhat protective against underuse in the preperiod (adjusted odds ratio (AOR) = 0.78, 95% confidence interval (CI) = 0.46-1.34; P = .37), but more so and significantly in the postperiod (AOR = 0.41, 95% CI = 0.18-0.93; P = .03). Having prescription insurance was more protective in the post- than in the preperiod (less gastroprotective agent underuse; adjusted ratio of OR = 0.53, 95% CI = 0.22-1.29; P = .16), but this increased protection was not statistically significant.ConclusionIn older daily NSAID users at high risk of PUD, having prescription insurance and adequate gastroprotective use was more common in the post- than in the preperiod.

BackgroundThe cerebellum plays an important role in mobility and cognition. However, it is unclear which regions of the cerebellum are associated with gait speed and information-processing ability in older adults without overt brain damage.MethodsCross-sectional associations between cerebellar gray matter volumes (GMV), gait speed, and information-processing ability were explored in 231 community-dwelling adults (mean age: 83 years, 48% black, 58% female). We measured gait speed on an automated walkway and information-processing ability on the Digit Symbol Substitution test (DSST). Total and regional cerebellar GMV was measured on 3T-magnetic resonance imaging. Lobar GMV of the cerebellum, obtained by an automated parcellation process, were aggregated based on the cognitive (lobules VI, VII, VIII and crus I, II), sensorimotor (lobules II, IV, V), and vestibular (lobules IX and X) functions ascribed to the cerebellar regions.ResultsLarger cerebellar GMV correlated with faster gait speed and superior DSST scores (both p < .001) independent of age, gender, atrophy, and small vessel disease. After adjusting for age, gender, and atrophy, larger cognitive cerebellar GMV correlated with both faster gait speed (p = .04) and higher DSST scores (p < .001), larger sensorimotor cerebellar GMV correlated significantly with DSST alone (p = .02), and the vestibular cerebellar GMV with neither. The association between cognitive cerebellar GMV and gait speed was no longer significant after adjusting for DSST score in the linear regression models.ConclusionsThe relationship between gait speed and cerebellar GMV is influenced by information-processing ability, and this relationship is stronger in subregions ascribed to cognitive than vestibular or sensorimotor functions.

BackgroundKidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure.Study designRetrospective cohort study.Setting & participants2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort.PredictorsRatios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively).OutcomesIncident heart failure over a median follow-up of 12 years.ResultsMedian values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51).LimitationsGeneralizability to other populations is uncertain.ConclusionsHigher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.

AimsThe contribution of heart failure (HF) unrelated to vascular disease to the overall HF burden in older adults is not well characterized. This was investigated in this study.Methods and resultsWe assessed HF incidence and outcomes in 2895 participants of the Health ABC Study (age 74 ± 3 years, 48.4% men, 41.4% black) in relation to vascular disease (coronary, peripheral, or cerebrovascular disease) either present at baseline or developed prior to HF. During 11.4 years follow-up, 493 participants developed HF; 134 (27.2%) in participants without any prior vascular disease and 177 (36.8%) without coronary disease. Both baseline [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.9-2.8] and incident vascular disease (HR 4.3, 95% CI 3.6-5.2) were associated with HF. During a median follow-up of 2.1 years after HF onset, 67.5% participants died. Annual mortality after HF development was 21.3% in those with compared with 24.6% in those without vascular disease (HR 1.11, 95% CI 0.87-1.43; P = 0.399). There were 658 all-cause (436.3/1000 person-years) and 523 HF-related (346.4/1000 person-years) hospitalizations after HF development. There was no significant difference in hospitalizations between those with and without vascular disease [rate ratio (RR) 1.04, 95% CI 0.86-1.24 for all-cause, and RR 0.84 95% CI 0.69-1.02 for HF hospitalization]. HF with preserved EF was more common in participants without vascular disease (67.0% vs. 55.0%, P = 0.040).ConclusionA significant proportion of HF in older adults develops without prior vascular disease. Outcomes for these patients are poor compared with those with preceding vascular disease. These data suggest the need for more targeted HF prediction and prevention efforts.

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI

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.

Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower gray matter integrity measured by mean diffusivity (standardized beta=0.16; p=0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both β=0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease.

BackgroundInformation about the prevalence and correlates of self-reported medication nonadherence using multiple measures in older adults with chronic cardiovascular conditions is needed.ObjectiveTo examine the prevalence and correlates of self-reported medication nonadherence among community-dwelling elders with chronic cardiovascular conditions.MethodsParticipants (n = 897) included members from the Health, Aging and Body Composition Study with coronary heart disease, diabetes mellitus, and/or hypertension at Year 10. Self-reported nonadherence was measured by the 4-item Morisky Medication Adherence Scale (MMAS-4) and 2-item cost-related nonadherence (CRN-2) scale at Year 11. Factors (demographic, health status, and access to care) were examined for association with the MMAS-4 and then for association with the CRN-2 scale.ResultsNonadherence per the MMAS-4 and CRN-2 scale was reported by 40.7% and 7.7% of participants, respectively, with little overlap (3.7%). Multivariable logistic regression analyses found that black race was significantly associated with nonadherence per the MMAS-4 (P = 0.002) and the CRN-2 scale (P = 0.005). Other correlates of nonadherence per the MMAS-4 (with independent associations) included having cancer (P = 0.04), a history of falls (P = 0.02), sleep disturbances (P = 0.04) and having a hospitalization in the previous 6 months (P = 0.005). Conversely, being unmarried (P = 0.049), having worse self-reported health (P = 0.04) and needs being poorly met by income (P = 0.02) showed significant independent associations with nonadherence per the CRN-2 scale.ConclusionsSelf-reported medication nonadherence was common in older adults with chronic cardiovascular conditions and only one factor - race - was associated with both types. The research implication of this finding is that it highlights the need to measure both types of self-reported nonadherence in older adults. Moreover, the administration of these quick measures in the clinical setting should help identify specific actions such as patient education or greater use of generic medications or pill boxes that may address barriers to medication nonadherence.

Antioxidant enzymes play an important role in the defense against oxidative stress in the lung and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sequence variation in genes encoding antioxidant enzymes may alter susceptibility to COPD by affecting longitudinal change in lung function in adults. We genotyped 384 sequence variants in 56 candidate genes in 1281 African American and 1794 European American elderly adults in the Health, Aging, and Body Composition study. Single-marker associations and gene-by-smoking interactions with rate of change in FEV₁ and FEV₁/FVC were evaluated using linear mixed-effects models, stratified by race/ethnicity. In European Americans, rs17883901 in GCLC was statistically significantly associated with rate of change in FEV₁/FVC; the recessive genotype (TT) was associated with a 0.9% per year steeper decline (P = 4.50 × 10(-5)). Statistically significant gene-by-smoking interactions were observed for variants in two genes in European Americans: the minor allele of rs2297765 in mGST3 attenuated the accelerated decline in FEV₁/FVC in smokers by 0.45% per year (P = 1.13 × 10(-4)); for participants with greater baseline smoking pack-years, the minor allele of rs2073192 in IDH3B was associated with an accelerated decline in FEV₁/FVC (P = 2.10 × 10(-4)). For both genes, nominally significant interactions (P < 0.01) were observed at the gene level in African Americans (P = 0.007 and 4.60 × 10(-4), respectively). Nominally significant evidence of association was observed for variants in SOD3 and GLRX2 in multiple analyses. This study identifies two novel genes associated with longitudinal lung function phenotypes in both African and European Americans and confirms a prior finding for GCLC. These findings suggest novel mechanisms and molecular targets for future research and advance the understanding of genetic determinants of lung function and COPD risk.

BackgroundOlder blacks are less likely to receive guideline-recommended antilipemic therapy and achieve lipid control than older whites because, in part, of out-of-pocket costs. We sought to determine whether racial differences in antilipemic use and lipid control narrowed after Medicare Part D's implementation.MethodsThis before-after study included 1,091 black and white adults 70 years or older with coronary heart disease and/or diabetes mellitus from the Health Aging and Body Composition Study. Primary outcomes were antilipemic use and low-density lipoprotein cholesterol control. Key independent variables were race, time (pre-Part D vs post-Part D), and their interaction.ResultsBefore 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 ratio 1.07, 95% CI 0.79-1.45). Compared with 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 (adjusted ratio of the odds ratio 0.82, 95% CI 0.51-1.33).ConclusionAlthough antilipemic use increased after Medicare Part D for both races, this policy change was associated with a change neither in lipid control for either racial group nor in the racial differences in antilipemic use or lipid control.

BackgroundPreventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals.MethodsThis was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization.ResultsThe crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15%). The 30-day and 1-year mortality were 16.5% and 31.5%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38% of pneumonia cases occurred in adults < 65 years of age. The 30-day and 1-year mortality were 12.5% and 25.7% in those < 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance.ConclusionsPneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model.

ObjectivesTo identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization of community-dwelling older adults.DesignProspective observational cohort study.SettingMemphis, Tennessee, and Pittsburgh, Pennsylvania.ParticipantsOf 3,075 well-functioning community-dwelling adults aged 70 to 79 enrolled in the Health, Aging, and Body Composition Study from 1997 to 1998, 1,441 had complete data in the data set of all variables used, a dental examination within 6 months of baseline, and were eligible for this study.MeasurementsThe primary outcome was pneumonia requiring hospitalization through 2008.ResultsOf 1,441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male sex (hazard ratio (HR) = 2.07, 95% confidence interval (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 percentage of predicted forced expiratory volume in 1 minute (moderate vs mild lung disease or normal lung function, HR = 1.78, 95% CI = 1.28-2.48; severe lung disease vs mild lung disease or normal lung function, HR = 2.90, 95% CI = 1.51-5.57) were nonmodifiable 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 cases of pneumonia were attributed to incident mobility limitation and 10.3% to a mean oral plaque score of 1 or greater.ConclusionIncident mobility limitation and higher mean oral plaque score were two modifiable risk factors that 22% of pneumonia requiring hospitalization could be attributed to. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults.

ObjectivesThe goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors.BackgroundSeveral studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups.MethodsWe undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects.ResultsOf 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p < 0.001) for coronary heart disease, 1.54 (95% CI: 1.34 to 1.78; p < 0.001) for stroke, and 1.45 (95% CI: 1.30 to 1.61; p < 0.001) for CVD. Associations stratified according to sex, diabetes, and hypertension were similar but decreased with age (1.89, 1.77, 1.36, and 1.23 for age ≤50, 51 to 60, 61 to 70, and >70 years, respectively; pinteraction

Early menopause affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of early menopause is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies in 3493 early menopause cases and 13598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait were also associated with early menopause and POI (Primary Ovarian Insufficiency). Thus early menopause has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the SNP arrays was estimated to account for approximately 30% of the variance in EM. The association between the combined 17 variants and the risk of early menopause was greater than the best validated non-genetic risk factor, smoking.

Background and purposeArterial stiffness is a measure of subclinical cardiovascular disease and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults.MethodsA total of 2488 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 examination at baseline and repeated at years 3, 5, 8, and 10. Lower Modified Mini-Mental State examination 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 1331 participants, to examine cognitive impairment defined as a decrease of ≥5 points after 9 years. We adjusted for sociodemographics, Apoe4, and cardiovascular disease risk factors.ResultsThe annual decrease in Modified Mini-Mental State examination scores was 0.30 points at low PWV (95% confidence interval [CI], -0.37 to -0.22), 0.46 points at middle PWV (95% CI, -0.54 to -0.39), and 0.45 points at high PWV (95% CI, -0.53 to -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 (odds ratio [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 with low PWV.ConclusionsHigh arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline.