Chronic kidney disease as a risk factor for peripheral nerve impairment in older adults: A longitudinal analysis of Health, Aging and Body Composition (Health ABC) study.

INTRODUCTION: Sensory and motor nerve deficits are prevalent in older adults and are associated with loss of functional independence. We hypothesize that chronic kidney disease predisposes to worsening sensorimotor nerve function over time. MATERIALS AND METHODS: Participants were from the Health, Aging and Body Composition Study (N = 1121) with longitudinal data between 2000-01 (initial visit) and 2007-08 (follow-up visit). Only participants with non-impaired nerve function at the initial visit were included. The predictor was presence of CKD (estimated GFR ≤ 60 ml/min/1.73m2) from the 1999-2000 visit. Peripheral nerve function outcomes at 7-year follow-up were 1) Motor: "new" impairments in motor parameters (nerve conduction velocity NCV < 40 m/s or peroneal compound motor action potential < 1 mv) at follow-up, and 2) Sensory: "new" impairment defined as insensitivity to standard 10-g monofilament or light 1.4-g monofilament at the great toe and "worsening" as a change from light to standard touch insensitivity over time. The association between CKD and "new" or "worsening" peripheral nerve impairment was studied using logistic regression. RESULTS: The study population was 45.9% male, 34.3% Black and median age 75 y. CKD participants (15.6%) were older, more hypertensive, higher in BMI and had 2.37 (95% CI 1.30-4.34) fold higher adjusted odds of developing new motor nerve impairments in NCV. CKD was associated with a 2.02 (95% CI 1.01-4.03) fold higher odds of worsening monofilament insensitivity. CKD was not associated with development of new monofilament insensitivity. CONCLUSIONS: Pre-existing CKD leads to new and worsening sensorimotor nerve impairments over a 7-year time period in community-dwelling older adults.

Trunk Muscle Composition 2 Months After Hip Fracture: Findings From the Baltimore Hip Studies.

OBJECTIVE: To determine if hip fracture patients would have smaller cross-sectional area (CSA) and lower radiological attenuation (suggesting greater fat infiltration) in all trunk muscles as compared to older adults without hip fractures. DESIGN: Cross-sectional analysis of computed tomography (CT) scans. SETTING: Clinical imaging facility. PARTICIPANTS: Forty-one white participants (19 men, 22 women) from the Baltimore Hip Studies seventh cohort at 2 months postfracture were compared to 693 white participants (424 men, 269 women) from the Health, Aging and Body Composition (Health ABC) study at the year 6 visit (N=734). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Trunk muscle CSA and attenuation values were obtained from a single 10-mm, axial CT scan completed at the L4-L5 disc space in each participant. RESULTS: The hip fracture cohort had significantly smaller CSA for all trunk muscles (range: 12.1%-38% smaller) compared to the Health ABC cohort (P<.01), with the exception of the rectus abdominus muscle in men (P=.12). But, hip fracture patients, particularly female patients, had higher attenuation levels (lower intramuscular fat) in all trunk muscles (P<.0001). CONCLUSIONS: Findings are consistent with atrophy of the trunk muscles in the hip fracture population without a high level of intramuscular fat. Future work should evaluate the role of trunk muscle composition in the functional recovery of older adults after hip fracture.

Metabolites Associated With Risk of Developing Mobility Disability in the Health, Aging and Body Composition Study.

Background: Metabolic pathways that give rise to functional decline and mobility disability in older adults are incompletely understood. Methods: To identify metabolic perturbations that may affect functional decline, nontargeted metabolomics was used to measure 350 metabolites in baseline plasma from 313 black men in the Health ABC Study (median age 74 years). Usual gait speed was measured over 20 m. Cross-sectional relationships between gait speed and metabolites were explored with partial correlations adjusted for age, study site, and smoking status. Risk of incident mobility disability (two consecutive reports of severe difficulty walking quarter mile or climb 10 stairs) over 13 years of follow-up was explored with Cox regression models among 307 men who were initially free of mobility disability. Significance was determined at p ≤ .01 and q (false discovery rate) ≤ 0.30. Results: Two metabolites were correlated with gait speed: salicylurate (r = -.19) and 2-hydroxyglutarate (r = -.18). Metabolites of amino acids and amino acid degradation (indoxy sulfate; hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.09-2.03, symmetric dimethylarginine; HR = 3.58, 95% CI = 1.57-8.15, N-carbamoyl beta-alanine; HR = 1.91, 95% CI = 1.16-3.14, quinolinate; HR = 2.56, 95% CI = 1.65-3.96) and metabolites related to kidney function (aforementioned symmetric dimethylarginine and indoxy sulfate as well as creatinine; HR = 5.91, 95% CI = 2.06-16.9, inositol; HR = 2.70, 95% CI = 1.47-4.97) were among the 23 metabolites associated with incident mobility disability. Conclusions: This study highlights the potential role of amino acid derivatives and products and kidney function early in the development of mobility disability and suggests metabolic profiles could help identify individuals at risk of functional decline.

Chronic kidney disease and peripheral nerve function in the Health, Aging and Body Composition Study.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor mobility. Peripheral nerve function alterations play a significant role in low mobility. We tested the hypothesis that early CKD is associated with altered sensory, motor and autonomic nerve function. METHODS: Participants in the Health, Aging and Body Composition cohort who had kidney function measures in Year 3 (1999-2000) and nerve function measurements at Year 4 (2000-01) were analyzed (n = 2290). Sensory (vibration threshold, monofilament insensitivity to light and standard touch), motor [compound motor action potentials (CMAPs), nerve conduction velocities (NCVs)] and autonomic (heart rate response and recovery after a 400-m walk test) nerve function as well as participant characteristics were compared across cystatin C- and creatinine-based estimated glomerular filtration rate categorized as ≤60 (CKD) or >60 mL/min/1.73 m2 (non-CKD). The association between CKD and nerve function was examined with logistic regression adjusted for covariates. RESULTS: Participants with CKD (n = 476) were older (77 ± 3 versus 75 ± 3 years; P < 0.05) and had a higher prevalence of diabetes (20.6% versus 13.1%; P < 0.001). CKD was associated with higher odds for vibration detection threshold {odds ratio [OR] 1.7 [95% confidence interval (CI) 1.1-2.7]} and light touch insensitivity [OR 1.4 (95% CI 1.1-1.7)]. CMAPs and NCVs were not significantly different between CKD and non-CKD patients. In adjusted analyses, participants with CKD had higher odds of an abnormal heart rate response [OR 1.6 (95% CI 1.1-2.2)] and poor heart rate recovery [OR 1.5 (95% CI 1.1-2.0)]. CONCLUSIONS: CKD is associated with changes in sensory and autonomic nerve function, even after adjustment for demographics and comorbidities, including diabetes. Longitudinal studies in CKD are needed to determine the contribution of nerve impairments to clinically important outcomes.

Low blood pressure levels for fall injuries in older adults: the Health, Aging and Body Composition Study.

Fall injuries cause morbidity and mortality in older adults. We assessed if low blood pressure (BP) is associated with fall injuries, including sensitivity analyses stratified by antihypertensive medications, in community-dwelling adults from the Health, Aging and Body Composition Study (N = 1819; age 76.6 ± 2.9 years; 53% women; 37% black). Incident fall injuries (N = 570 in 3.8 ± 2.4 years) were the first Medicare claims event from clinic visit (7/00-6/01) to 12/31/08 with an ICD-9 fall code and non-fracture injury code, or fracture code with/without a fall code. Participants without fall injuries (N = 1249) were censored over 6.9 ± 2.1 years. Cox regression models for fall injuries with clinically relevant systolic BP (SBP; ≤ 120, ≤ 130, ≤ 140, > 150 mmHg) and diastolic BP (DBP; ≤ 60, ≤ 70, ≤ 80, > 90 mmHg) were adjusted for demographics, body mass index, lifestyle factors, comorbidity, and number and type of medications. Participants with versus without fall injuries had lower DBP (70.5 ± 11.2 vs. 71.8 ± 10.7 mmHg) and used more medications (3.8 ± 2.9 vs. 3.3 ± 2.7); all P < 0.01. In adjusted Cox regression, fall injury risk was increased for DBP ≤ 60 mmHg (HR = 1.25; 95% CI 1.02-1.53) and borderline for DBP ≤ 70 mmHg (HR = 1.16; 95% CI 0.98-1.37), but was attenuated by adjustment for number of medications (HR = 1.22; 95% CI 0.99-1.49 and HR = 1.12; 95% CI 0.95-1.32, respectively). Stratifying by antihypertensive medication, DBP ≤ 60 mmHg increased fall injury risk only among those without use (HR = 1.39; 95% CI 1.02-1.90). SBP was not associated with fall injury risk. Number of medications or underlying poor health may account for associations of low DBP and fall injuries.

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). RESULTS: Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS: The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).

Development of a standardized definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

BACKGROUND: Bleeding is the major risk of aspirin treatment, especially in the elderly. A consensus definition for clinically significant bleeding (CSB) in aspirin primary prevention trials is lacking in the literature. METHODS: This paper details the development, modification, application, and quality control of a definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a primary prevention trial of aspirin in 19,114 community-dwelling elderly men and women. In ASPREE a confirmed bleeding event needed to meet criteria both for substantiated bleeding and clinical significance. Substantiated bleeding was defined as: 1) observed bleeding, 2) a reasonable report of symptoms of bleeding, 3) medical, nursing or paramedical report, or 4) imaging evidence. Bleeding was defined as clinically significant if it: 1) required transfusion of red blood cells, 2) required admission to the hospital for >24 h, or prolonged a hospitalization, with bleeding as the principal reason, 3) required surgery to stop the bleeding, or 4) resulted in death. Bleeding sites were subclassified as upper gastrointestinal, lower gastrointestinal, intracranial (hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, extradural hematoma, or other), or other sites. Potential events were retrieved from medical records, self-report or notification from treating doctors. Two reviewers adjudicated each event using electronic adjudication software, and discordant cases were reviewed by a third reviewer. Adjudication rules evolved to become more strictly defined as the trial progressed and decision rules were added to assist with frequent scenarios such as post-operative bleeding. CONCLUSIONS: This paper provides a detailed methodologic description of the development of a standardized definition for clinically significant bleeding and provides a benchmark for development of a consensus definition for future aspirin primary prevention trials. TRIAL REGISTRATION: ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and on clinicaltrials.gov (NCT01038583).

Mobility Trajectories at the End of Life: Comparing Clinical Condition and Latent Class Approaches.

OBJECTIVES: To assess mobility disability trajectories before death in a large sample of very old adults using two analytical approaches to determine how well they corresponded. DESIGN: Decedent sample from the Health, Aging and Body Composition (Health ABC) Study. Data were collected between 1997 and 2015. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Individuals randomly selected from well-functioning white Medicare beneficiaries and all black community residents meeting age criteria (70-79) (N = 3,075). MEASUREMENTS: Participants were interviewed in person or by phone at least every six months throughout the study. Of the 1,991 participants who died by the end of the study, 1,410 had been interviewed for 3 years before death, including an interview 6 months before dying. We analyzed self-reported mobility collected prospectively at 6-month intervals during the last 3 years of life. We derived trajectories in two ways: by averaging decline within decedent groups prespecified according to clinical conditions and by estimating trajectory models using maximum-likelihood semiparametric modeling. RESULTS: Ninety-eight percent of decedents were classified according to 4 prespecified clinical conditions (sudden death, terminal, organ failure, frailty), which produced groups with different characteristics. Five disability trajectories were identified: late decline, progressive disability, moderate disability, early decline, and persistent disability. Disability trajectory and clinical condition grouping confirmed previous research but were only marginally related. CONCLUSION: Derived disability trajectories and grouping according to clinical condition provide useful information about different facets of the end-of-life experience. The lack of fit between them suggests a need for greater attention to heterogeneity in disability in the period before death.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

Background: Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. Methods: We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Results: Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Conclusions: Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

Longitudinal Associations Between Walking Speed and Amount of Self-reported Time Spent Walking Over a 9-Year Period in Older Women and Men.

Background: Age-related limitations in mobility and decreased physical activity appear to be linked cross-sectionally; however, large-scale, longitudinal analyses of the associations between age-related changes in mobility and engagement in physical activity are lacking. In this longitudinal study, we hypothesized that early mobility limitations would contribute to later decreases in physical activity to a larger degree than the reciprocal association of early decreases in physical activity to later mobility limitations. Methods: Participants were 2,876 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 52% women; 39% black) studied over a 9-year period. Usual walking speed and self-reported physical activity (based on minutes per week of walking) were assessed at Years 0 (ie, baseline), 4, and 9. A cross-lagged, longitudinal model assessed the bidirectional associations between walking speed and physical activity over time. Results: Early change in walking speed between Years 0 and 4 predicted late change in physical activity between Years 4 and 9 (ß = .13 p < .001). However, early change in physical activity did not predict late change in walking speed (ß = -.01, p = .79). The difference between these two predictive associations was highly significant (p < .001). Associations were independent of baseline demographic and physical health variables, as well as longitudinal changes in grip and quadriceps strength. Conclusions: The results suggest declining walking speed as a precursor to declining engagement in physical activity, but the converse association was not evident. Improving walking speed may be a method to increase physical activity among elderly individuals.

Three Year Functional Trajectories Among Old Age Survivors and Decedents: Dying Eliminates a Racial Disparity.

BACKGROUND: Long-term trajectories of disability comparing decedents and survivors and differences by race have not been assessed. OBJECTIVE: To examine self-reported difficulty in walking a quarter mile and the need for assistance with activities of daily living (ADL) beginning 3 years before death among decedents and age- and gender-matched survivors. DESIGN: A case-control sample drawn from the Health, Aging and Body Composition Study (Health ABC). Data were collected between 1997 and 2015. PARTICIPANTS: Of the 1991 participants who died by the end of the study, 1410 were interviewed for 3 years prior to death, including an interview 6 months before dying. Of these, 1379 decedents were successfully matched by age and gender with 1379 survivors and tracked over the same 3-year period. MAIN MEASURES: Self-reported difficulty walking a quarter mile and the ability to perform activities of daily living without assistance (bathing, dressing, transferring). KEY RESULTS: Decedents (mean age at death, 84) increased in mobility disability from 44.1% 3 years before death to 69.4% 6 months before death and in ADL disability from 32.9% to 58.4%. Among survivors, mobility disability increased from 31.4% to 40.7% and ADL disability from 17.4% to 31.4%. The proportion of decedents and survivors with mobility disability differed significantly in adjusted models at all assessment points (p < 0.0001). African-American survivors were significantly more disabled than White survivors at all points (p < 0.0001), but trajectories of disability among decedents did not differ by race in the last 18 months of life (p = 0.35). CONCLUSIONS: Trajectories of self-reported disability differ between survivors and decedents. Older adults who died were more disabled 3 years before death and also had a greater risk of increasing disability over each subsequent 6-month assessment. The gap in disability between African Americans and Whites was erased in the final 1 to 1.5 years before death.

Estimation of Skeletal Muscle Mass Relative to Adiposity Improves Prediction of Physical Performance and Incident Disability.

Purpose: We assessed the discrimination of lean mass estimates that have been adjusted for adiposity for physical functioning deficits and prediction of incident disability. Methods: Included were 2,846 participants from the Health, Aging and Body Composition Study with available whole-body dual energy absorptiometry measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2). Age-, sex-, and race-specific Z-Scores and T-Scores were determined by comparison to published reference ranges. ALMI values were adjusted for FMI (ALMIFMI) using a novel published method. Sex-stratified analyses assessed associations between lean mass estimates and the physical performance score, ability to complete a 400-meter walk, grip strength, and incident disability. Dichotomized definitions of low lean for age and sarcopenia were examined and their performance compared to the ALM-to-BMI ratio. Results: Compared to ALMI T-Scores and Z-Scores, the ALMIFMI scores demonstrated stronger associations with physical functioning, and were similarly associated with grip strength. Greater FMI Z-Scores and T-Scores were associated with poor physical functioning and incident disability. Definitions of low lean for age and sarcopenia using ALMIFMI (compared to ALMI) better discriminated those with poor physical functioning and a greater risk of incident disability. The ALM-to-BMI ratio was modestly associated with grip strength and physical performance, but was not associated with completion of the 400-meter walk or incident disability, independent of adiposity and height. Conclusion: Estimation of skeletal muscle mass relative to adiposity improves correlations with physical performance and prediction of incident disability suggesting it is an informative outcome for clinical studies.

Olfaction and incident Parkinson disease in US white and black older adults.

OBJECTIVE: To investigate olfaction in relation to incident Parkinson disease (PD) in US white and black older adults. METHODS: The study included 1,510 white (mean age 75.6 years) and 952 black (75.4 years) participants of the Health, Aging, and Body Composition study. We evaluated the olfaction of study participants with the Brief Smell Identification Test (BSIT) in 1999-2000. We retrospectively adjudicated PD cases identified through August 31, 2012, using multiple data sources. We used multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average of 9.8 years of follow-up, we identified a total of 42 incident PD cases, including 30 white and 12 black participants. Overall, poor sense of smell, as indicated by a lower BSIT score, was associated with higher risk of PD. Compared with the highest tertile of BSIT (t3), the HR was 1.3 (95% CI 0.5-3.6) for the second tertile (t2) and 4.8 (95% CI 2.0-11.2) for the lowest tertile (t1) (ptrend < 0.00001). Further analyses revealed significant associations for incident PD in both the first 5 years of follow-up (HRt1/[t2+t3] 4.2, 95% CI 1.7-10.8) and thereafter (HRt1/[t2+t3] 4.1, 95% CI 1.7-9.8). This association appeared to be stronger in white (HRt1/[t2+t3] 4.9, 95% CI 2.3-10.5) than in black participants (HRt1/[t2+t3] 2.5, 95% CI 0.8-8.1), and in men (HRt1/[t2+t3] 5.4, 95% CI 2.3-12.9) than in women (HRt1/[t2+t3] 2.9, 95% CI 1.1-7.8). CONCLUSIONS: Poor olfaction predicts PD in short and intermediate terms; the possibility of stronger associations among men and white participants warrants further investigation.

Impact of Incident Heart Failure on Body Composition Over Time in the Health, Aging, and Body Composition Study Population.

BACKGROUND: Prevalence of heart failure (HF) increases significantly with age, coinciding with age-related changes in body composition that are common and consequential. Still, body composition is rarely factored in routine HF care. METHODS AND RESULTS: The Health, Aging, and Body Composition study is a prospective cohort study of nondisabled adults. Using yearly dual-energy x-ray absorptiometry, body composition was assessed in the Health, Aging, and Body Composition study over 6 years, comparing those who developed incident HF versus those who did not. Among 2815 Health, Aging, and Body Composition participants (48.5% men; 59.6% whites; mean age, 73.6±2.9 years), 111 developed incident HF over the 6-year study period. At entry into the Health, Aging, and Body Composition study, men and women who later developed HF had higher total body mass when compared with those versus those who did not develop HF (men, 80.9±10 versus 78.6±12.9 kg, P=0.05; women, 72.7±15.0 versus 68.2±14.2 kg, P=0.01, respectively). However, after developing HF, loss of total lean body mass was disproportionate; men with HF lost 654.6 versus 391.4 g/y in non-HF participants, P=0.02. Loss of appendicular lean mass was also greater with HF (-419.9 versus -318.2 g/y; P=0.02), even after accounting for total weight change. Among women with HF, loss of total and appendicular lean mass were also greater than in non-HF participants but not to the extent seen among men. CONCLUSIONS: Incident HF in older adults was associated with disproportionate loss of lean mass, particularly among men. Prognostic implications are significant, with key sex-specific inferences on physical function, frailty, disability, and pharmacodynamics that all merit further investigation.

Slowing gait and risk for cognitive impairment: The hippocampus as a shared neural substrate.

OBJECTIVE: To identify the shared neuroimaging signature of gait slowing and cognitive impairment. METHODS: We assessed a cohort of older adults (n = 175, mean age 73 years, 57% female, 65% white) with repeated measures of gait speed over 14 years, MRI for gray matter volume (GMV) at year 10 or 11, and adjudicated cognitive status at year 14. Gait slowing was calculated by bayesian slopes corrected for intercepts, with higher values indicating faster decline. GMV was normalized to intracranial volume, with lower values indicating greater atrophy for 10 regions of interest (hippocampus, anterior and posterior cingulate, primary and supplementary motor cortices, posterior parietal lobe, middle frontal lobe, caudate, putamen, pallidum). Nonparametric correlations adjusted for demographics, comorbidities, muscle strength, and knee pain assessed associations of time to walk with GMV. Logistic regression models calculated odds ratios (ORs) of gait slowing with dementia or mild cognitive impairment with and without adjustment for GMV. RESULTS: Gait slowing was associated with cognitive impairment at year 14 (OR per 0.1 s/y slowing 1.47; 95% confidence interval 1.04-2.07). The right hippocampus was the only region that was related to both gait slowing (ρ = -0.16, p = 0.03) and cognitive impairment (OR 0.17, p = 0.009). Adjustment for right hippocampal volume attenuated the association of gait slowing with cognitive impairment by 23%. CONCLUSIONS: The association between gait slowing and cognitive impairment is supported by a shared neural substrate that includes a smaller right hippocampus. This finding underscores the value of long-term gait slowing as an early indicator of dementia risk.

Long-term changes in time spent walking and subsequent cognitive and structural brain changes in older adults.

Previous studies have shown that more active older adults have better cognition and brain health based on a variety of structural neuroimaging measures. Nevertheless, the effects of maintaining physical activity (PA) over an extended period of time on future changes in older adults' cognition and brain structure are unknown. Participants were 141 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 60% female; 42% black) studied over a 13-year period. PA (self-reported time spent walking) was assessed annually from years 1 to 10. Magnetic resonance imaging with diffusion tensor was performed at years 10 and 13. Time spent walking decreased on average by 8.4% annually from year 1 to year 10. Independent of initial time spent walking, demographics, and APOE e4 status, better maintenance of time spent walking over the decade predicted less reduction in hippocampal volume (p = 0.03), smaller increases in global gray matter mean diffusivity and white matter axial diffusivity (p < 0.01), and maintenance of general cognitive performance (p < 0.01). Maintenance of cognitive performance was associated with smaller increases in white matter axial diffusivity (p < 0.01). PA at baseline and at year 10, as well as changes in PA over a 5-year period, was less predictive of future changes in brain structure and cognition. Thus, how PA levels change over longer periods of aging may be an important contributor to cognitive and neural protection.

Catechol-O-Methyltransferase Genotype and Gait Speed Changes over 10 Years in Older Adults.

OBJECTIVES: To determine the association between catechol-O-methyltransferase (COMT) genotype and 6-m walk time and to determine whether these associations are quadratic in nature, similar to previously reported U-shaped associations between dopamine and gait and cognition. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Black (n = 850) and white (n = 1,352) men and women with a mean age of 73.5 ± 2.85 at baseline. MEASUREMENTS: Mixed models were used to assess the association between the COMT genotype and 6-m walk time, cross-sectionally and longitudinally over 10 years. Models were assessed unstratified and stratified according to race because allele distributions were different between white and black participants. RESULTS: There was a significant U-shaped association between COMT genotype and 6-m walk time: those with higher (Val/Val) and lower (Met/Met) dopamine slowed more over 10 years (0.22 ± 0.02 seconds per visit and 0.23 ± 0.02 seconds per visit, respectively) than those with the intermediate (Met/Val) dopamine (0.20 ± 0.02 seconds per visit) (P = .005). Stratified results showed a significant relationship in black (P = .01) but not white (P = .15) participants. CONCLUSION: These findings indicate a role of dopaminergic regulation of gait speed in community-dwelling older adults and of prefrontal cortex involvement in gait performance. Future work should investigate the molecular integrity of dopaminergic networks and gait changes over time and structural changes in the brain with COMT and gait decline in older adults.

Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD.

BACKGROUND AND OBJECTIVES: Although anthropometric measures of body fat are associated with development of CKD, they may not be able to distinguish between various forms of fat and therefore may be less accurate than computed tomography (CT) measures. We compared the association of CT and anthropometric measures of obesity with kidney outcomes in the Health Aging and Body Composition Study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants were recruited from March of 1997 through July of 1998. CT measures included visceral abdominal fat (VAT), subcutaneous adipose tissue (SAT), and intermuscular fat area (IMAT), whereas anthropometric measures included waist circumference (WC) and body mass index (BMI). Kidney outcomes included kidney function (KF) decline (30% decrease in eGFRcysC in follow-up at either year 3 or 10) or incident CKD (follow-up eGFRcysC≤60 ml/min per 1.73 m2 in individuals with baseline GFR>60 ml/min per 1.73 m2). Multivariable logistic regression models and Poisson regression models were used to evaluate the association with decline in KF and incident kidney disease, respectively. We also assessed for the independent associations among the exposure measures by including them in the same model. RESULTS: Two-thousand four-hundred and eighty-nine individuals were included. Mean age was 74±3 years, 49% were men, 39% were black, 59% were hypertensive, and 15% were diabetic. KF decline occurred in 17% of the population, whereas incident CKD also occurred in 17% of those at risk. In continuous models, SAT, VAT, IMAT, BMI, and WC (per SD increase) were all significantly associated with KF decline. There was a significant interaction between VAT and CKD with regard to KF decline (P=0.01). Only VAT, BMI, and WC were associated with incident CKD. Only VAT remained a significant risk factor for incident CKD when other exposure variables were included in the same model. There was no association between any measure of obesity and kidney outcomes when creatinine values at years 3 and 10 were used to estimate changes in eGFR. CONCLUSIONS: Anthropometric measures of body fat appear to provide as consistent estimates of KF decline risk as CT measures in elders.

Associations of Musculoskeletal Pain With Mobility in Older Adults: Potential Cerebral Mechanisms.

BACKGROUND: Musculoskeletal 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. METHODS: Musculoskeletal 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). RESULTS: The associations of musculoskeletal pain with WMH (ß = .19, p < .05) and FA (ß = -.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. CONCLUSIONS: Cerebral 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.

The Prevalence of Anosmia and Associated Factors Among U.S. Black and White Older Adults.

BACKGROUND: Olfactory impairment is common among older adults; however, data are largely limited to whites. METHODS: We conducted pooled analyses of two community-based studies: the Atherosclerosis Risk in Communities study (ARIC, 1,398 blacks and 4,665 whites), and the Health, Aging, and Body Composition study (Health ABC, 958 blacks and 1,536 whites) to determine the prevalence of anosmia and associated factors for black and white older adults in the United States. RESULTS: The overall prevalence of anosmia was 22.3% among blacks and 10.4% among whites. Blacks had a markedly higher odds of anosmia compared to whites in age and sex adjusted analyses (odds ratio [OR] 2.96, 95% confidence interval [CI] = 2.59-3.38). In both blacks and whites, higher anosmia prevalence was associated with older age and male sex. The highest prevalence was found in black men 85 years or older (58.3%), and the lowest in white women aged 65-69 years (2.4%). Higher education level, lower cognitive score, ApoE ε4, daytime sleepiness, poorer general health status, lower body mass index, and Parkinson disease were associated with higher prevalence of anosmia in one or both races. However, the racial difference in anosmia remained statistically significant after adjusting for these factors (fully adjusted OR = 1.76, 95%CI: 1.50-2.07). Results were comparable between the two cohorts. DISCUSSION: Anosmia is common in older adults, particularly among blacks. Further studies are needed to identify risk factors for anosmia and to investigate racial disparities in this sensory deficit.