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Background Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). Methods The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70–79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. Results After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. Conclusions Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure. [ABSTRACT FROM AUTHOR]

Increased β-adrenergic receptor activity has been hypothesized to cause bone loss in those with dementia. We investigated the effect of long-term β-blocker use on rate of bone loss in older adults with dementia. We used a linear mixed-effects model to estimate the relationship between long-term β-blocker use and rate of bone loss in participants from the Health Aging and Body Composition study. Records of 1198 participants were analyzed, 44.7% were men. Among the men, 25.2% had dementia and 20.2% were on β-blockers, while in the women, 22.5% had dementia and 16.6% received β-blockers. In the 135 men with dementia, 23 were taking β-blockers, while 15 of 149 women with dementia were using β-blockers. In men with dementia, β-blocker users had 0.00491 g/cm2 less bone mineral density (BMD) loss per year at the femoral neck (i.e., 0.63% less loss per year) than non-users (p < 0.05). No differences were detected in women with or without dementia and men without dementia. β-blockers may be protective by slowing down bone loss in older men with dementia. [ABSTRACT FROM AUTHOR]

Rationale & objectivesLower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored.Study designCase-cohort study.Setting & participantsWell-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study.PredictorSerum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry.OutcomesMajor kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up.Analytic approachBaseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression.ResultsDuring 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations.LimitationsObservational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race.ConclusionsLower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.

Background: Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile.Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0 m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk.Results: We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13-1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12-1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10-1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12-2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85-1.66).Conclusions: High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated. [ABSTRACT FROM AUTHOR]

BackgroundAlthough vitamin D has been mechanistically linked to insulin secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D levels confer an increased risk of impaired glucose metabolism. We evaluated the relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and abnormal hemoglobin A1c (A1c) (≥6.5%) in community-dwelling older persons and examined whether this relationship differed according to race.MethodsParticipants were 2,193 persons of age 70-79 years at Year 1 (52% women; 37% black) in the Health, Aging, and Body Composition study who had clinic visits at Years 2 and 4. Logistic regression analyses, adjusted for potential confounders, were used to evaluate the association between vitamin D insufficiency and abnormal A1c 2 years later. Interaction of race and vitamin D insufficiency was tested.ResultsA total of 665 (30%) and 301 (14%) of the participants had vitamin D insufficiency at Year 2 and abnormal A1c at Year 4, respectively. After controlling for demographics, other potential confounders, and diabetes status at Year 4 (n = 477 diabetics), we found that vitamin D insufficiency was associated with an increased likelihood of having abnormal A1c (odds ratio = 1.56; 95% CI: 1.03-2.37). We also found that this relationship persisted among the 1,765 participants without diabetes in Year 2 (odds ratio = 2.33; 95% CI: 1.00-5.40). Findings did not differ by race.ConclusionsVitamin D insufficiency was associated with abnormal A1c levels among black and white older persons independent of diabetes status. Future studies are needed to establish the temporal relationship between vitamin D and A1c in diverse samples of older persons.

BackgroundAbnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.ObjectiveTo determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.MethodsWe examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.ResultsAmong 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.ConclusionsA prolonged QT interval is associated with an increased risk of incident AF.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels—one for ordered categories and one for nominal categories—that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia. [ABSTRACT FROM AUTHOR]

Background: In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Methods: Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Results: Data from 140 patients were available for review. The cohort had a median age of 61 years (range 4589) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Conclusion: Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.

Objectives: To examine the relationship between end-of-life (EOL) treatment preferences and recent hospitalization or emergency department (ED) care in the very old. Design: Quarterly telephone follow-up of participants in the EOL in the Very Old cohort. Setting: The EOL in the Very Old Age cohort drew from 1403 participants in the Health, Aging, and Body Composition (Health ABC) study who were alive in year 15 of follow-up. 87.5% ( n = 1227) were successfully recontacted and enrolled. Participants: Preferences for treatment at the EOL and reported hospital and ED use were examined for 1118 participants (18% involving proxy reports) over 6 months, 1021 (16% with proxy reports) over 12 months, and 945 (23% with proxy reports) over 18 months in 6-month intervals. Measurements: Preferences for eight EOL treatments, elicited once each year; hospitalization and ED use reported every six months. Results: Preferences for more aggressive treatment (endorsing ≥5 of 8 options) were not significantly associated with inpatient or ED treatment. Inpatient and ED treatment were not associated with changes in preferences for aggressive EOL treatment over 12 months. Conclusion: Alternative measures that tap attitudes toward routine care, rather than EOL treatment preferences, may be more highly associated with healthcare utilization. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether hearing impairment (HI) in older adults is associated with the development of frailty and falls. Method: Longitudinal analysis of observational data from the Health, Aging and Body Composition study of 2,000 participants aged 70 to 79 was conducted. Hearing was defined by the pure-tone-average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better hearing ear. Frailty was defined as a gait speed of <0.60 m/s and/or inability to rise from a chair without using arms. Falls were assessed annually by self-report. Results: Older adults with moderate-or-greater HI had a 63% increased risk of developing frailty (adjusted hazard ratio [HR] = 1.63, 95% confidence interval [CI] = [1.26, 2.12]) compared with normal-hearing individuals. Moderate-or-greater HI was significantly associated with a greater annual percent increase in odds of falling over time (9.7%, 95% CI = [7.0, 12.4] compared with normal hearing, 4.4%, 95% CI = [2.6, 6.2]). Discussion: HI is independently associated with the risk of frailty in older adults and with greater odds of falling over time. [ABSTRACT FROM AUTHOR]

Objective: To identify the neuromuscular attributes that are associated with self-reported mobility status among older primary care patients., Design: Cohort study., Setting: Metropolitan-based health care system., Participants: Community-dwelling primary care patients aged ≥65 years (N=430), with self-reported modification of mobility tasks resulting from underlying health conditions., Interventions: Not applicable., Main Outcome Measures: Basic and Advanced Lower Extremity Function as measured by the Late Life Function and Disability Instrument., Results: We constructed multivariable linear regression models evaluating both outcomes. For Basic Lower Extremity Function, leg strength, leg velocity, trunk extensor muscle endurance, and ankle range of motion (ROM) were statistically significant predictors (P<.001, R(2)=.21). For Advanced Lower Extremity Function, leg strength, leg strength asymmetry, leg velocity, trunk extensor muscle endurance, and knee flexion ROM were statistically significant predictors (P<.001, R(2)=.39). Sensitivity analyses conducted using multiple imputations to account for missing data confirmed these findings., Conclusions: This analysis highlights the relevance and importance of 5 categories of neuromuscular attributes: strength, speed of movement, ROM, asymmetry, and trunk stability. It identifies novel attributes (leg velocity and trunk extensor muscle endurance) relevant to mobility and highlights that impairment profiles vary by the level of mobility assessed. These findings will inform the design of more thorough and potentially more effective disability prevention strategies., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)