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Background: The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. Methods: This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence‐limiting physical disability at trial enrolment. This analysis examined the association of baseline and time‐varying allopurinol use with persistent physical disability and new‐onset frailty in participants with gout at baseline (self‐report or use of any anti‐gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional‐hazards models were used for main analyses. Results: This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow‐up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23–0.92, p = 0.03). The strength of the association was modestly attenuated in the time‐varying analysis (Adjusted HR 0.56, 0.29–1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62–1.12; FI: Adjusted HR 0.96, 0.74–1.24) or time‐varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69–1.24; FI: Adjusted HR 1.02, 0.78–1.33). Conclusions: Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty. [ABSTRACT FROM AUTHOR]

Background: Efforts to minimize medication risks among older adults include avoidance of potentially inappropriate medications (PIMs). However, most PIMs research has focused on older people in aged or inpatient care, creating an evidence gap for community‐dwelling older adults. To address this gap, we investigated the impact of PIMs use in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial cohort. Methods: Analysis included 19,114 community‐dwelling ASPREE participants aged 70+ years (65+ if US minorities) without major cardiovascular disease, cognitive impairment, or significant physical disability. PIMs were defined according to a modified 2019 AGS Beers Criteria. Cox proportional‐hazards regression models were used to estimate the association between baseline PIMs exposure and disability‐free survival, death, incident dementia, disability, and hospitalization, with adjustment for sex, age, country, years of education, frailty, average gait speed, and comorbidities. Results: At baseline, 7396 (39% of the total) participants were prescribed at least one PIM. Compared with those unexposed, participants on a PIM at baseline were at an increased risk of persistent physical disability (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.21, 1.80) and hospitalization (adjusted HR 1.26, 95% CI 1.20, 1.32), but had similar rates of disability‐free survival (adjusted HR 1.02; 95% CI 0.93, 1.13) and death (adjusted HR 0.92, 95% CI 0.81, 1.05). These effects did not vary by polypharmacy status in interaction analyses. PIMs exposure was associated with higher risk of disability followed by hospitalization (adjusted HR 1.92, 95% CI 1.25, 2.96) as well as vice versa (adjusted HR 1.54, 95% CI 1.15, 2.05). PPIs, anti‐psychotics and benzodiazepines, were associated with increased risk of disability. Conclusions: PIMs exposure is associated with subsequent increased risk of both incident disability and hospitalization. Increased risk of disability prior to hospitalization suggests that PIMs use may start the disability cascade in healthy older adults. Our findings emphasize the importance of caution when prescribing PIMs to older adults in otherwise good health. [ABSTRACT FROM AUTHOR]

Background: Dietary supplement and complementary and alternative medication (CAM) use can contribute to drug interactions, polypharmacy, nonadherence with prescription medications, and healthcare expenses, whereas evidence supporting benefits of using these products is sparse. There is a lack of current published literature describing the patterns or predictors of their use in community‐dwelling older adults. Materials and Methods: We performed a cross‐sectional analysis of community‐dwelling adults from Australia and the US, aged 70 years and older (65 years for US minorities), enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study. At study enrollment, eligible participants were required to be without concurrent 5‐year life‐limiting illness and free of documented evidence of cardiovascular disease, dementia, or significant physical disability. During the final study visit, a questionnaire was administered to collect information about supplement/CAM use. Data from 15,729 participants who completed this questionnaire between January 2017 and January 2018 were analyzed. Descriptive statistics were used to report the prevalence and types of products used. Factors associated with use were determined using multivariate regression. Results: Mean age of respondents was 79.6 years; 56.4% were female, 88.8% were from Australia, 56.5% reported 12 years of education or less, and 98.7% were living at home. Two‐thirds (66.2%) of participants reported use of one or more supplement/CAM in the previous month. Products most commonly used included vitamin D (33.8% of participants), fish oil (22.7%), calcium (20.6%), glucosamine (14.8%), and multivitamin (12.9%). Female sex, US residency, higher education, polypharmacy (prescription medications), and frailty (in women) were significantly associated with higher use of supplements/CAMs. Conclusions: Dietary supplement and CAM use is common among community‐dwelling older adults in the United States and Australia. Given the high prevalence of use, collaboration between healthcare providers and older adult patients is important to insure safe and optimal use of these products. [ABSTRACT FROM AUTHOR]

I Background: i The ASPREE (ASPirin in Reducing Events in the Elderly) trial was a randomized, double-blind, placebo-controlled primary prevention trial of aspirin in 19 114 community-dwelling persons aged 70 years and older (>=65 years in U.S. racial minorities). I Objective: i To investigate the effect of aspirin cessation versus continuation on disability-free survival and other clinical outcomes in a post hoc analysis of ASPREE participants who were regularly taking aspirin before trial enrollment. [Extracted from the article]

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: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.Design: Prospective cohort study.Setting: Primary care (Australia and USA).Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people. [ABSTRACT FROM AUTHOR]

The association of different antihypertensive regimens with blood pressure (BP) control is not well-described among community-dwelling older adults with low comorbidity. We examined antihypertensive use and BP control in 10 062 treated hypertensives from Australia and the United States (US) using baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Renin-angiotensin system (RAS) drugs were the most prevalently used antihypertensive in both countries (Australia: 81.7% of all regimens; US: 62.9% of all regimens; P < .001). Diuretics were the next most commonly used antihypertensive in both countries, but were more often included in regimens of US participants (48.9%, vs 33.3% of regimens in Australia; P < .001). Among all antihypertensive classes and possible combinations, monotherapy with a RAS drug was the most common regimen in both countries, but with higher prevalence in Australian than US participants (35.9% vs 20.9%; P < .001). For both monotherapy and combination users, BP control rates across age, ethnicity, and sex were consistently lower in Australian than US participants. After adjustment for age, sex, ethnicity, and BMI, significantly lower BP control rates remained in Australian compared to US participants for the most commonly used classes and regimens (RAS blocker monotherapy: BP control = 45.5% vs 54.2%; P = .002; diuretic monotherapy: BP control = 45.2% vs 64.5%; P = .001; and RAS blocker/diuretic combo: BP control = 50.2% vs 65.6%; P = .001). Our findings highlight variation in antihypertensive use in older adults treated for hypertension, with implications for BP control. Differences in BP control that were observed may be influenced, in part, by reasons other than choice of specific regimens. [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: The neurocognitive effect of statins in older adults remain uncertain.Objectives: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.Methods: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer's disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer's disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.Results: Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).Conclusions: In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials. [ABSTRACT FROM AUTHOR]

Background: There is clinical uncertainty regarding the benefits and harms of prescribing statins in healthy subjects ≥70 years of age.Objectives: The aim of this study was to examine the association among statins, dementia-free and disability-free survival, and cardiovascular disease (CVD) among healthy older adults using data from the ASPREE (Aspirin in Reducing Events in the Elderly) trial.Methods: ASPREE was a randomized trial of 19,114 community-dwelling persons in Australia and the United States ≥65 years of age and free of documented CVD, dementia, and disability. Data were collected for those ≥70 years of age, and participants who took statins at baseline were compared with those who did not using Cox proportional hazards regression with inverse probability weighting. The primary outcome, referred to as "disability-free survival," was a composite of all-cause mortality, dementia, or persistent physical disability. Other outcomes included the individual components of the composite outcome, major adverse cardiovascular events, fatal CVD, myocardial infarction, and stroke.Results: Of the 18,096 included participants (median age 74.2 years, 56.0% women), 5,629 took statins at baseline. Over a median follow-up period of 4.7 years, baseline statin use was not associated with disability-free survival or with the risk for all-cause mortality or dementia. However, it was associated with lower risks for physical disability and all cardiovascular outcomes.Conclusions: Among healthy community-dwelling adults ≥70 years of age, statin use may be beneficial for preventing physical disability and CVD but not beneficial for prolonging disability-free survival or avoiding death or dementia. Future clinical trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Keywords: aging; aspirin; body weight EN aging aspirin body weight 1110 1112 3 04/20/20 20200331 NES 200331 A recent meta-analysis[1] of individual patient data from several randomized, controlled trials evaluating aspirin for the prevention of primary or secondary cardiovascular events found that the protective effect of low-dose aspirin (<=100 mg) was limited to individuals weighing <70 kg, driven by lean body mass (LBM) but not body mass index (BMI).[1] Given the limited number of people >=70 years of age who were included in the meta-analysis[1] and calls for validation of these findings,[2],[3] we investigated whether body habitus modulated the efficacy of aspirin in a post hoc analysis of the ASPREE trial (Aspirin in Reducing Events in the Elderly).[4] ASPREE randomized 19 114 older participants to daily 100-mg enteric-coated aspirin (9525) or matched placebo (9589) and followed them up for a median of 4.7 years for disability-free survival and other clinical outcomes.[4] Trial participants were community-dwelling Australian (16 703) and US (2411) men and women who were >=70 years of age at enrollment or >=65 years of age for US blacks and Hispanics. At baseline, anthropometric indexes (mean±SD) of body weight, BMI, waist circumference, and LBM in the aspirin versus placebo groups were 77.0±15.1 kg versus 77.0±14.8 kg, 28.1±4.8 kg/m SP 2 sp versus 28.1±4.7 kg/m SP 2 sp , 97±13 cm versus 97±13 cm, and 49.8±8.3 kg versus 49.9±8.2 kg, respectively. Larger BMI or waist circumference or LBM also did not alter the effect of aspirin on the risk of cardiovascular disease or major hemorrhage (Figure). [Extracted from the article]