Shari M. Ling

Physical and Cognitive Performance and Burden of Anticholinergics, Sedatives, and ACE Inhibitors in Older Women

Polypharmacy, common in older people, confers both risk of adverse outcomes and benefits. We assessed the relationship of commonly prescribed medications with anticholinergic and sedative effects to physical and cognitive performance in older individuals. The study population comprised 932 moderately to severely disabled community‐resident women aged 65 years or older who were participants in the Womens Health and Aging Study I. A scale based on pharmacodynamic principles was developed and utilized as a measure of drug burden. This was related to measures of physical and cognitive function. After adjusting for demographics and comorbidities, anticholinergic drug burden was independently associated with greater difficulty in four physical function domains with adjusted odds ratios (95% confidence interval (CI)) of 4.9 (2.0–12.0) for balance difficulty; 3.2 (1.5–6.9) for mobility difficulty; 3.6 (1.6–8.0) for slow gait; 4.2 (2.0–8.7) for chair stands difficulty; 2.4 (1.1–5.3) for weak grip strength; 2.7 (1.3–5.4) for upper extremity limitations; 3.4 (1.7–6.9) for difficulty in activities of daily living; and 2.4 (95% CI, 1.1–5.1) for poor performance on the Mini‐Mental State Examination. Sedative burden was associated only with impaired grip strength (3.3 (1.5–7.3)) and mobility difficulty (2.4 (1.1–5.3)). The burden of multiple drugs can be quantified by incorporating the recommended dose regimen and the actual dose and frequency of drug taken. Anticholinergic drug burden is strongly associated with limitations in physical and cognitive function. Sedative burden is associated with impaired functioning in more limited domains. The risk associated with exposure of vulnerable older women to drugs with anticholinergic properties, and to a lesser extent those with sedative properties, implies that such drugs should not be used in this patient group without compelling clinical indication.

Abnormal body composition phenotypes in older rheumatoid arthritis patients: association with disease characteristics and pharmacotherapies.

OBJECTIVE To compare measures of body fat and lean mass and the prevalence of abnormal body composition phenotypes (sarcopenia, overfat, and sarcopenic obesity) in men and women with rheumatoid arthritis (RA) versus matched controls, and to explore the disease-related predictors of abnormal body composition in patients with RA. METHODS A total of 189 men and women with RA and 189 age-, sex-, and race-matched non-RA controls underwent dual-energy x-ray absorptiometry for measurement of total and regional body fat and lean mass. Continuous and categorical measures of body composition were compared between RA and control subjects by sex and according to categories of body mass index (BMI). Within the group of RA patients, demographic, lifestyle, and RA disease and treatment characteristics were compared for RA patients with healthy body composition versus those with abnormal body composition phenotypes. RESULTS Compared with non-RA controls, RA status was significantly associated with greater odds of sarcopenia, overfat, and sarcopenic obesity in women, but not in men. Relative differences in body composition phenotypes between RA and control subjects were greatest for patients in the normal weight BMI category (<25 kg/m(2)). Among RA characteristics, increasing joint deformity, self-reported disability scores, C-reactive protein levels, rheumatoid factor seropositivity, and a lack of current treatment with disease-modifying antirheumatic drugs were significantly associated with abnormal body composition. CONCLUSION Abnormal body composition phenotypes are overrepresented in patients with RA, particularly in those in the normal weight BMI range. RA-associated disease and treatment characteristics contribute to this increase in abnormal body composition.

Drug Burden Index Score and Functional Decline in Older People

BACKGROUND The Drug Burden Index (DBI), a measure of exposure to anticholinergic and sedative medications, has been independently associated with physical and cognitive function in a cross-sectional analysis of community-dwelling older persons participating in the Health, Aging and Body Composition study. Here we evaluate the association between DBI and functional outcomes in Health, Aging and Body Composition study participants over 5 years. METHODS DBI was calculated at years 1 (baseline), 3, and 5, and a measure of the area under the curve for DBI (AUCDB) over the whole study period was devised and calculated. Physical performance was measured using the short physical performance battery, usual gait speed, and grip strength. The association of DBI at each time point and AUCDB with year 6 function was analyzed in data from participants with longitudinal functional measures, controlling for sociodemographics, comorbidities, and baseline function. RESULTS Higher DBI at years 1, 3, and 5 was consistently associated with poorer function at year 6. On multivariate analysis, a 1-unit increase in AUCDB predicted decreases in short physical performance battery score of .08 (P=.01), gait speed of .01 m/s (P=.004), and grip strength of .27 kg (P=.004) at year 6. CONCLUSION Increasing exposure to medication with anticholinergic and sedative effects, measured with DBI, is associated with lower objective physical function over 5 years in community-dwelling older people.

Knee X-Ray Image Analysis Method for Automated Detection of Osteoarthritis

We describe a method for automated detection of radiographic osteoarthritis (OA) in knee X-ray images. The detection is based on the Kellgren-Lawrence (KL) classification grades, which correspond to the different stages of OA severity. The classifier was built using manually classified X-rays, representing the first four KL grades ( normal, doubtful, minimal, and moderate). Image analysis is performed by first identifying a set of image content descriptors and image transforms that are informative for the detection of OA in the X-rays and assigning weights to these image features using Fisher scores. Then, a simple weighted nearest neighbor rule is used in order to predict the KL grade to which a given test X-ray sample belongs. The dataset used in the experiment contained 350 X-ray images classified manually by their KL grades. Experimental results show that moderate OA (KL grade 3) and minimal OA (KL grade 2) can be differentiated from normal cases with accuracy of 91.5% and 80.4%, respectively. Doubtful OA (KL grade 1) was detected automatically with a much lower accuracy of 57%. The source code developed and used in this study is available for free download at www.openmicroscopy.org.

Prevalence of significant knee pain among older Americans: results from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To assess the prevalence of persistent knee pain among older adults in the US.

Influence of Leptin, Adiponectin, and Resistin on the Association Between Abdominal Adiposity and Arterial Stiffness

BACKGROUND Adiposity is associated with arterial stiffness, and both adiposity and arterial stiffness independently predict morbidity and mortality. Because adipocytes account for most adipokine production, the objectives of this study were to examine the influence of adipokines such as leptin, adiponectin, and resistin on the relationship between abdominal adiposity and arterial stiffness. METHODS This is a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA). Adiposity was measured as kilograms of abdominal adipose tissue using dual-energy X-ray absorptiometry (DXA). Arterial stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Leptin, adiponectin, and resistin were assayed in fasting serum samples. The influence of adipokines on the relationship between adiposity and arterial stiffness by adipokines was examined using standard mediation pathway analysis. RESULTS Among 749 participants ages 26-96 years (mean age 67, 52% men, 27% black), abdominal adiposity was positively associated with PWV (relative ratio (RR) = 1.04, P = 0.02), after adjusting for potential confounders but was attenuated and no longer significant after adjusting for leptin (RR = 0.99, P = 0.77). The relationship between adiposity and PWV was not substantially influenced by adiponectin (RR = 1.03, P = 0.06) or resistin (RR = 1.05, P = 0.010). Leptin (RR = 1.02, P < 0.001), resistin (RR = 0.92, P < 0.0001), and adiponectin (RR = 0.97, P = 0.004), but not abdominal adiposity (RR = 1.00, P = 0.94), retained significant associations with PWV when adjusting for each other and confounders. CONCLUSIONS Our findings are consistent with the hypothesis that leptin explains, in part, the observed relationship between abdominal adiposity and arterial stiffness. Adiponectin, leptin, and resistin are independent correlates of PWV.

Serum protein signatures detect early radiographic osteoarthritis

OBJECTIVE To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident. METHODS Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case-control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques. RESULTS Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA. CONCLUSIONS Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years.

Age-Related Mechanical Work Expenditure During Normal Walking: the Baltimore Longitudinal Study of Aging

The aim of this cross-sectional study was to delineate age-associated kinematic and kinetic gait patterns of normal walking, and to test the hypothesis that older adults exhibit gait patterns that reduce generative mechanical work expenditures (MWEs). We studied 52 adult Baltimore Longitudinal Study of Aging participants (means age 72+/-9, from 60 to 92 years) who could walk 4m unaided. Three-dimensional kinematic and kinetic parameters assessed during rotation-defined gait periods were used to estimate MWEs for the rotation of lower extremities about the medial-lateral (ML) and anterior-posterior (AP) axes of proximal joints, which represent MWEs in the AP and ML sides, respectively. Relationships between gait parameters and age were examined using regression analysis with adjustments for walking speed, sex, height, and weight. Older age was associated with slower self-selected walking speed (p<0.001), shorter stride length (p<0.001), and greater propensity of landing flat-footed (p=0.003). With older age, hip generative MWE for thigh rotation was lower about the AP axis (hip abduction and adduction) during stance (p=0.010) and higher about the ML axis (hip extension and flexion) during late stance (p<0.001). Knee absorptive MWE for shank rotation about the AP axis (knee abduction and adduction) during early stance was also lower with older age (p<0.003). These age-related gait patterns may represent a compensatory effort to maintain balance and may also reflect mobility limitations.

Early detection of radiographic knee osteoarthritis using computer-aided analysis

OBJECTIVE To determine whether computer-based analysis can detect features predictive of osteoarthritis (OA) development in radiographically normal knees. METHOD A systematic computer-aided image analysis method weighted neighbor distances using a compound hierarchy of algorithms representing morphology (WND-CHARM) was used to analyze pairs of weight-bearing knee X-rays. Initial X-rays were all scored as normal Kellgren-Lawrence (KL) grade 0, and on follow-up approximately 20 years later either developed OA (defined as KL grade=2) or remained normal. RESULTS The computer-aided method predicted whether a knee would change from KL grade 0 to grade 3 with 72% accuracy (P<0.00001), and to grade 2 with 62% accuracy (P<0.01). Although a large part of the predictive signal comes from the image tiles that contained the joint, the region adjacent to the tibial spines provided the strongest predictive signal. CONCLUSION Radiographic features detectable using a computer-aided image analysis method can predict the future development of radiographic knee OA.

Age-Associated Changes in Motor Unit Physiology: Observations From the Baltimore Longitudinal Study of Aging

OBJECTIVE To examine motor unit characteristics (size and firing rate) associated with aging. DESIGN Cross-sectional, observational. SETTING Community. PARTICIPANTS Baltimore Longitudinal Study of Aging participants (N=102), aged 22.2 to 94.1 years, were studied. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Surface-represented motor unit size and firing rate were collected from the vastus medialis during knee extension at 10%, 20%, 30%, and 50% of each subjects maximum isometric voluntary contraction (MVC). RESULTS MVC declined with older age (P<.0001). Adjusting for differences in MVC, both firing rate and motor unit size per newton force generated began to increase in the 6th decade of life. Motor unit size increased per newton force to a greater extent than firing rate. Those over the age of 75 years also activated significantly larger motor units per unit force (P=.04). Relative to force generated, the average firing rate began increasing at 57.8+/-3.4 years and between 50.2 and 56.4 years (+/-4y) for motor unit size. CONCLUSIONS The size of motor units and firing rates used to achieve a given force changes with age, particularly after middle age. Whether these changes precede, follow, or occur concurrent to age-related modifications in muscle structure and contractile properties or sarcopenia is not known.