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Background: Osteoporosis and Alzheimer's disease are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The aim of the current study is to investigate the relationship between circulating levels of bone-related biomarkers and cognition.Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18 months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging. Baseline plasma concentrations of bone-related biomarkers, including undercarboxylated, carboxylated, and total osteocalcin, parathyroid hormone, C-terminal telopeptide of collagen 1 (CTX-1), procollagen type 1 amino-terminal propeptide, osteoprotegrin, osteopontin, Dickkopf WNT signaling pathway inhibitor 1 (Dkk1), sclerostin, and amyloid β peptides (Aβ40 and Aβ42), were measured.Results: Using sex, age, and education-adjusted mixed-effects models, we found that baseline levels of TNF-related apoptosis-inducing ligand (TRAIL; p < .001), Dkk1 (p = .014), and CTX-1 (p = .046) were related to the annual rate of change of global cognition over the 18 month follow-up. In cognitive domain-specific analysis, baseline TRAIL was found to be positively related to the annual rate of change in episodic (p < .001) and working memory (p = .016), and baseline Dkk1 was positively related to semantic memory (p = .027) and negatively related to working memory (p = .016).Conclusions: These results further confirm the link between bone and brain health and suggest that circulating levels of bone-related biomarkers may have diagnostic potential to predict worsening cognition. [ABSTRACT FROM AUTHOR]

Background. Maintaining spatial movement through the environment is an important feature of healthy aging. We examined whether being licensed to drive is associated with maintaining spatial movement in older persons initially reporting maximum spatial mobility. Methods. From the Rush Memory and Aging Project, 571 nondemented, community-dwelling older persons were identified with (i) baseline data on driving status, (ii) baseline report of spatial mobility to the largest life space zone, and (iii) at least one annual follow-up evaluation. Incident constriction of life space was the primary outcome of interest. Results. Over an average follow-up of 4.3 years, 303 participants reported incident constriction of life space. In a proportional hazards model adjusted for age, sex, and education, having a valid driver's license at baseline was associated with a decreased hazard of reporting a life space constriction (hazard ratio = 0.39; 95% confidence interval = 0.29–0.54). Results were unchanged after controlling for number of vascular risk factors and vascular diseases, low visual acuity, social isolation, and gait speed. Of participants reporting incident life space constriction, 188 subsequently reported reexpansion of spatial mobility to the largest zone of life space. Having a valid driver's license was associated with a greater likelihood of life space recovery (hazard ratio = 2.00; 95% confidence interval = 1.27–3.17). Conclusion. In older persons, having a valid driving license was associated with reduced hazard of reporting life space constriction and a greater likelihood of life space recovery if incident life space constriction occurred. [ABSTRACT FROM PUBLISHER]

Background. Identifying mobility disability risk factors may facilitate development of interventions promoting functional independence in older persons. We tested the hypothesis that musculoskeletal pain is associated with first occurrence of severe mobility disability. Methods. In a prospective observational study at 40 community-based sites, 759 older Catholic clergy in the Rush Religious Orders Study without baseline dementia, stroke, Parkinson's disease, or severe performance-based mobility disability (defined as gait speed less than or equal to 0.4 m/s) and at least one follow-up mobility evaluation were evaluated over a mean of 8.5 (SD = 3.8) years. All participants were queried about musculoskeletal pain in the year before baseline and underwent annual assessment of mobility. Results. Using a proportional hazards model adjusted for age, sex, and education, the hazard for incident severe mobility disability was greater for participants reporting pain in the year before baseline (odds ratio = 1.47, 95% confidence interval = 1.17–1.85). Results were unchanged after adjusting for self-reported mobility disability, gait speed, depressive symptoms, body mass index, physical activity, chronic medical conditions, and analgesic use. Compared with no report of musculoskeletal pain, musculoskeletal pain in one or two areas was associated with a 30% greater hazard for incident disability (odds ratio = 1.31, 95% confidence interval = 1.00–1.70). Musculoskeletal pain in three or more areas was associated with an 80% greater hazard for incident disability (odds ratio = 1.80, 95% confidence interval = 1.31–2.47). In participants without baseline self-reported mobility disability (n = 486), musculoskeletal pain was associated with greater hazard for incident self-reported mobility disability (odds ratio = 1.38, 95% confidence interval = 1.11–1.73). Conclusion. In older persons, musculoskeletal pain is associated with incident mobility disability. [ABSTRACT FROM PUBLISHER]

Background. Factors contributing to gait difficulties in elderly persons are considered to be multifactorial and are not well understood. The purpose of this study was to examine the association of blood pressure (BP) with change in lower limb function in older persons. Methods. Eight hundred eighty-eight older Catholic clergy members without baseline dementia or Parkinson's disease were recruited from about 40 groups across the United States. At baseline, BP was measured, the presence of vascular diseases and diabetes was recorded, cognitive function was assessed, and medications were inspected. At baseline and subsequent annual visits, gait and balance were assessed using performance-based tasks from which a previously established composite measure of lower limb function was derived. Results. In a general estimating equation analysis controlling for age, education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was associated with greater decline in lower limb function (estimate of interaction = -6.35 x 10-3, standard error = 2.49 x 10-3, p=.011), Thus, on average, lower limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in persons with an SBP of 120 mmHg. This effect was unchanged after controlling for baseline vascular diseases, diabetes, or cognition. However, censoring individuals who developed stroke during the study made the relationship between SBP and change in lower limb function nonsignificant. Conclusions. SBP may be associated with decline in lower limb function in older persons. [ABSTRACT FROM AUTHOR]

Background The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals. Methods This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. Results We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3–3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (p interaction < .05). Conclusions There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that urinary incontinence (UI) is associated with incident parkinsonism in older adults.Methods: We used data from 2,617 older persons without dementia. Assessment included baseline self-report UI and annual structured exam which assessed parkinsonian signs, motor performances, cognitive function, and self-report disabilities. We used a series of Cox proportional hazards models to examine the association of UI with parkinsonism and adverse health outcomes and a mixed-effect model to examine the association of UI with the annual rate of cognitive decline. In decedents, regression models were used to examine if UI proximate to death was related to postmortem indices of neuropathologies.Results: At baseline, more than 45% of participants reported some degree of UI. Over an average of nearly 8 years of follow-up, UI was associated with incident parkinsonism (hazard ratio [HR] = 1.07, 95% CI = 1.02, 1.12), death (HR = 1.07, 95% CI = 1.03, 1.11), incident ADL disability (HR = 1.11, 95% CI = 1.07, 1.16), and incident mobility disability (HR = 1.07, 95% CI = 1.02, 1.13). UI was not related to incident MCI (HR = 1.02, 95% CI = 0.97, 1.07), incident AD dementia (HR = 1.00, 95% CI = 0.95, 1.05) or to the rate of cognitive decline (Estimate = -.002, standard error = .002, p = .167). In 1,024 decedents with brain autopsy, UI proximate to death was related to PD pathology (Lewy body pathology and nigral neuronal loss), but not Alzheimer's disease pathology or other age-related neuropathologies.Conclusion: UI in older adults is associated with incident parkinsonism and may identify older adults at risk for accumulating PD brain pathology. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial.Methods: In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data.Results: Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups.Conclusions: Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty. [ABSTRACT FROM AUTHOR]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [ABSTRACT FROM AUTHOR]

Background: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks.Methods: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12).Results: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis.Discussion: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. [ABSTRACT FROM AUTHOR]

Background. Anemia is associated with increased mortality risk. The impact of mildly low hemoglobin concentration (Hb) on risk for mortality remains unclear, especially among blacks. We examined the racial differences between Hb and mortality. Methods. This was a population-based study conducted from 1993 through 2006, in a geographically defined community of Chicago, Illinois. A stratified, random sample of 1806 participants 65 years old or older and 50% black, who were participating in the Chicago Health Aging Project and underwent clinical evaluation. Mortality was ascertained using the National Death Index. Cox proportional hazard models were used to assess the independent relation of Hb to mortality risk. I Results. The proportion of participants with anemia by World Health Organization (WHO) criteria (Hb < 13.0 g/dL for men and < 12.0 g/dL for women) was 39% among blacks, and 17% among whites. Blacks had lower mean Hb (12.6 ± 1.5 g/dL) than did whites (13.5 ± 1.5 g/dL). In multivariable analysis, anemia was associated with increased mortality risk in blacks (hazard ratio [HR], 1.90; 95% confidence interval [II, 1.43-2.53) and in whites (HR, 1.85; 95% Cl, 1.32-2.59). Among blacks, Hb 0-0.9 g/dL below the anemia threshold is associated with increased mortality risk compared to Hb 0-0.9 g/dL above the anemia cutoff (HR, 1.84; 95% Cl, 1.21-2.79), Hb 1.1-2.0 g/dL above the anemia cutoff (HR, 1.35; 95% Cl, 0.88-2.05) and Hb 2.1-3.0 g/dL above the anemia cutoff (HR, 2.24; 95% Cl, 1.12-4.47). The terms for interaction between black ethnicity/race and anemia suggested that blacks did not have a statistically significant difference in mortality risk compared to whites. Subgroup analyses of interaction terms suggested that Hb 0.1-1.0 g/dL above anemia cutoff group, blacks may have lower mortality risk compared to whites in the mildly low normal ranges of Hb (p = .02). Conclusion. Both anemia by WHO criteria and mild reductions in Hb were related to increased risk of mortality in older blacks and whites. [ABSTRACT FROM AUTHOR]