BACKGROUND:Blood pressure (BP) time in target range (TTR) predicts cardiovascular disease (CVD) in high-risk populations; however, TTR's predictive utility in older adults without prior CVD is uncertain. METHODS:We performed a post-hoc analysis of the ASPirin in Reducing Events in the Elderly trial and its observational follow-up. Systolic BP TTR for <140 and <130 mmHg was estimated for each participant using BPs from the first three visits. Participants with 0% or 100% TTR were categorized separately, and remaining participants grouped into tertiles using linear interpolation to estimate TTR. Cox proportional hazards models evaluated associations between TTR and adjudicated incident CVD and major adverse cardiovascular events (MACE) after the TTR estimation period, with 0% TTR as reference. RESULTS:Among 16,730 predominantly white Australian adults (mean age, 74 years) followed for a mean of 7.7 years after TTR estimation, 100% TTR <140 mmHg had reduced risk of CVD (HR, 0.81 [95% CI, 0.68-0.96]; P = .01), while 100% TTR <130 mmHg had reduced risks of CVD (HR, 0.82 [95% CI, 0.67-0.99]; P = .04) and MACE (HR, 0.72 [95% CI, 0.57-0.91]; P < .01). Associations were strongest among women, antihypertensive users, frail/pre-frail participants, and those younger than median age. Findings were consistent after adjusting for competing risk of non-CVD death, when the TTR estimation period was extended an additional year, and when estimated using proportion of individual visit BPs at target. CONCLUSIONS:Longer systolic BP TTR was associated with reduced risk of cardiovascular events in older adults, underscoring the importance of sustained BP control with aging.

BACKGROUND:We examined whether impaired kidney function, identified through elevated levels of urine albumin to creatinine ratio (UACR) or reduced estimated glomerular filtration rate (eGFR), is associated with hospitalisation or death due to heart failure (HF) in a large community-based cohort of older adults. METHODS:We included 17 834 participants from the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial and follow-up ASPREE eXTension observational study with complete baseline data on albuminuria and eGFR. HRs for hospitalisation due to HF (HHF), HF death, a composite outcome of HHF and HF death, and HF re-admission were calculated using Cox models adjusting for potential confounders. RESULTS:Over a median follow-up of 8.6 years, 354 (1.98%) participants had a first hospitalisation for HF and 147 (0.82%) died due to HF. Participants with albuminuria (UACR ≥3.0 mg/mmol; 11.3%) had higher risk for HHF, HF death and the combined HF outcome compared with those with no albuminuria (HRs 1.47 (95% CI 1.12 to 1.92), 1.55 (95% CI 1.04 to 2.33) and 1.33 (95% CI, 1.05 to 1.70), respectively). In participants with albuminuria, there was also an increased risk for re-admission due to HF (HR 1.30 (95% CI 1.03 to 1.65)), although there was no difference in risk of HF death. For eGFR, a U-shaped relationship was observed with increased risk of HHF, HF death and the HF composite outcome at both low (eg, <60 mL/min/1.73 m²) and high (eg, >90 mL/min/1.73 m²) eGFR levels. However, the association at high eGFR was not statistically significant and may reflect residual confounding. No association was observed between eGFR and HF re-admission. CONCLUSIONS:In this large cohort of older adults, albuminuria was associated with increased risk of HF outcomes, supporting its role in HF risk assessment. Low eGFR was also linked to higher risk of HHF, HF death and the HF composite outcome. Associations with high eGFR were not conclusive and should be considered hypothesis-generating.

BACKGROUND:Ascertaining the clinical relevance of reduced eGFR in older adults is challenging, particularly in those who may have decreased creatinine due to low muscle mass. This study investigated the potential of gait speed and grip strength (markers of muscle mass) to support the clinical interpretation of eGFR and its association with disability-free survival in older adults. METHODS:This was a cohort study of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized trial and the ASPREE-eXtension observational follow-up study. Participants were recruited from community-based clinics. ASPREE enrolled adults aged ≥70 years, with African American and Hispanic adults eligible from age ≥65 years, all of whom were free of significant co-morbidity at baseline. Baseline eGFR categories (<60, 60-79, ≥80mL/min/1.73m2) combined with gait speed (<or ≥1 m/s), and in separate models, baseline eGFR categories combined with grip strength (weak vs not weak), were used as explanatory variables. Outcomes were disability-free survival, all-cause mortality, independence-limiting physical disability, or dementia. Survival analyses with undertaken with reference to individuals with 'eGFR 60-79mL/min/1.73m2 and slow gait' or 'eGFR 60-79mL/min/1.73m2 and not weak'. RESULTS:There were 16,925 participants, median follow-up was 8.4 years (interquartile range [IQR]:2.7,9.6), mean age was 75.0±4.5 years, and median eGFR was 79mL/min (IQR:68,89). In the presence of normal gait speed or grip strength, eGFR <60mL/min/1.73m2 did not increase the risk for disability-free survival or its components. Slow gait or weak grip accompanying any eGFR was associated with reduced disability-free survival, increased mortality, or increased disability. E.g: participants with eGFR ≥80mL/min/1.73m2 and slow gait were at risk for dementia (HR:1.48, 95%CI:1.23-1.79). CONCLUSIONS:In older, initially healthy adults, assessment of gait speed and grip strength may provide additional context when examining associations between eGFR and disability-free survival and its individual components.

INTRODUCTION:Air pollution is linked to dementia, but evidence from low-exposure settings is limited. We examined sex-specific associations between long-term exposure to fine particulate matter ≤2.5 µm in diameter (PM2.5) and dementia risk in older adults living in Australia. METHODS:In 16,145 dementia-free Aspirin in Reducing Events in the Elderly (ASPREE) participants (≥70 years; median follow-up 10.3 years), Cox models assessed associations between 1-year mean PM2.5 (continuous and guideline-based categories) and incident dementia, adjusting for demographic, lifestyle, environmental, and genetic factors. Subgroup analyses by sex, apolipoprotein E genotype (APOE), and age were conducted. RESULTS:Overall associations were null, but with a trend for increased risk at exposures >10 versus ≤5 µg/m3. In subgroup analyses, positive associations were observed among females, with larger effect estimates at exposure >10 µg/m3, whereas associations remained null among males. No differences were observed across APOE genotypes or age groups. DISCUSSION:Findings suggest a threshold of >10 µg/m3 and heightened susceptibility in females. Further research in low-exposure settings is warranted.

BACKGROUND:Cerebral small vessel disease and alterations in retinal vascular calibre (RVC) are recognised precursors of stroke, dementia, and cognitive decline. We aimed to assess the effect of low-dose aspirin on white matter hyperintensity (WMH), a marker of cerebral small vessel disease, and changes in RVC. METHODS:We conducted a prospectively planned exploratory neurovascular substudy (ENVIS-ion) of the Aspirin in Reducing Events in the Elderly (ASPREE) double-blinded randomised clinical trial of 19 114 older adults (aged ≥70 years), who had no previous cardiovascular disease, stroke, or cognitive impairment at baseline. Participants were allocated to daily enteric-coated aspirin 100 mg or matching placebo using computer-generated randomisation and underwent MRI of the brain and fundus photography at two clinical trials sites in Australia at baseline and after 3 years. WMH and RVC measures were assessed by graders blinded to study treatment allocation. The effects of aspirin on total and regional WMH volumes (as a percentage of total brain volume) and RVC over time were analysed using linear models. ASPREE is registered with ClinicalTrials.gov, NCT01038583, and the International Standard Randomised Controlled Trial Number Registry, ISRCTN83772183. FINDINGS:Between April, 2010, and April, 2012, 610 participants from the eligible ASPREE cohort of 2346 individuals were enrolled in the ENVIS-ion substudy. Of the 610 participants (mean age 75·2 years [SD 4·1], 289 [47%] male and 321 [53%] female), 312 were assigned to receive aspirin and 298 to placebo. Over 3 years, the aspirin group had a greater increase in the percentage of deep WMH (β 0·14 [95% CI 0·01 to 0·27]) but there was no difference between aspirin and placebo groups in changes from baseline to 3 years in total brain WMH (0·05 [-0·02 to 0·11]) or periventricular WMH (0·03 [-0·03 to 0·09]). There was no evidence of an aspirin effect on RVC. The rate of major haemorrhage was higher in the aspirin arm for the ASPREE study (hazard ratio 1·38, 95% CI 1·18 to 1·62). INTERPRETATION:In this exploratory study, there was no evidence that low-dose aspirin in healthy older adults had any effect on RVC or attenuated the progression of WMH during a 3-year period. FUNDING:National Health and Medical Research Council of Australia.

The American Heart Association (AHA) recently introduced a new clinical entity; the cardiovascular-kidney-metabolic syndrome (CKMS), to promote a multi-disciplinary approach for chronic disease management. This study aims to investigate the relationship between CKMS and major adverse outcomes in older populations in primary care. This study utilized data from 18,367 community-dwelling individuals aged ≥ 65, free from prior cardiovascular disease (CVD). Participants were classified into four CKMS stages (stage 0-no CKMS risk factor to stage 3-high CKMS risk) at baseline based on the AHA definition. The association with 14 health outcomes was analysed using multivariable cause-specific hazard models. Additional stratifications were performed by social disadvantage, inflammation levels, and number of CKMS components within each stage to refine risk staging. Over a median follow-up of 8.6 years, the prevalence of CKMS stages 0 to 3 was 2.8

Background and ObjectivesHearing loss is a risk factor of cognitive decline and dementia. We sought to investigate the effect of hearing aid (HA) use on cognition and dementia risk in older adults with hearing impairment.MethodsWe emulated a target trial using data from Australian participants of the ASPirin in Reducing Events in the Elderly study. In the target trial, eligible participants were dementia-free, had moderate hearing impairment, and had no previous HA use. The treatment strategies were "use HAs" and "do not use HAs." Outcomes included overall cognition, dementia (DSM-IV criteria), and cognitive impairment (cognitive decline or dementia). The emulation used new HA prescription and frequency-of-use data measured by questionnaire, as well as cognition data from semiannual assessments over 7 years. Self-reported hearing problems were used as a proxy for moderate hearing impairment. Using the parametric g-formula, we estimated observational analogs of the intention-to-treat effect, using HA prescription to emulate allocation. Analyses for cognition outcomes were restricted to survivors. Multiple imputation was used for missing covariate and cognitive outcome data. We also emulated a second target trial with treatment strategies of (1) never, (2) rarely/sometimes, and (3) often/always use HAs.ResultsAcross imputed data sets, a median of 2,777 eligible individuals were included, with a median of 664 receiving a new HA prescription. The mean age was 75 years, and 48% were female. The estimated 7-year mean overall cognition scores among survivors were similar under HA prescription and no HA prescription (mean difference 0.03 SDs; 95% CI -0.14 to 0.21). The estimated 7-year risk of dementia was 5.0% under HA prescription and 7.5% under no HA prescription (risk ratio [RR] 0.67; 95% CI 0.37-0.97), and that of cognitive impairment was 36.1% under HA prescription and 42.4% under no HA prescription (RR 0.85; 95% CI 0.70-1.00). The risks of dementia and cognitive impairment were inversely associated with the frequency of HA use.DiscussionWe found that HA use in older people with hearing impairment may reduce dementia risk, although differences in age-related cognitive change were insubstantial. We cannot rule out residual confounding as an explanation for our findings. Long-term randomized trials of HAs for dementia risk are justified.Classification of EvidenceThis study provides Class III evidence that the use of hearing aids did not change overall cognitive scores in people 70 years and older with moderate hearing impairment as compared to those who used hearing aids.

BACKGROUND:Antibiotics are commonly prescribed in older community-dwelling adults, contributing to adverse effects, antimicrobial resistance and increased healthcare costs. Prescribing patterns in dementia are unclear, although healthcare use and goals of care change around diagnosis. OBJECTIVE:To describe trends in antibiotic dispensing and prevalence amongst Australians aged ≥70 years, compare dispensing between those with and without dementia and identify factors associated with dispensing. METHODS:We analysed data from 13 659 ASPREE and ASPREE-XT participants (2010-20). Antibiotic dispensing was assessed using Pharmaceutical Benefits Scheme records, with rates stratified by age group. Interrupted time-series analysis compared dispensing rates and the proportion of broad- versus narrow-spectrum antibiotics dementia case and matched controls (matched on time since randomisation, age and sex). Negative binomial regression identified factors associated with dispensing. RESULTS:Dispensing rates increased to 1651 per 1000 person-years (95% CI: 1604-99) by year 9. Annual prevalence averaged 47%. Broad-spectrum antibiotics were dispensed twice as often as narrow-spectrum. Individuals with dementia had higher dispensing both before and after diagnosis, but dementia was not independently associated with dispensing (IRR 1.06, 95% CI: 0.95-1.18). Female sex, polypharmacy, pre-frailty and higher depressive symptom scores were linked to higher dispensing, whilst hypertension, dyslipidaemia and alcohol use were linked to lower dispensing. CONCLUSIONS:Antibiotic dispensing in older adults remains high, dominated by broad-spectrum agents. Dementia was not independently associated with increased dispensing. Female sex, polypharmacy, pre-frailty and depressive symptoms identified groups who may benefit most from targeted antimicrobial stewardship interventions.

Acute kidney injury is a common complication of cardiac surgery and may lead to kidney failure. In a large sample sourced from national registries, we estimated the risk of kidney failure up to nine years following cardiac surgery and the associations with acute kidney injury, comorbidities and preoperative estimated glomerular filtration rate. Data were linked probabilistically between population-based registries to identify adults with kidney failure (commencement of long-term kidney replacement therapy) following cardiac surgery. Risk of kidney failure accounting for the competing risk of death was estimated from 30 days following surgery using Fine-Gray models. Surgeries from 2010 to 2018 were included (n = 90 605) with follow-up until the end of 2018. A total of 465 adults (0.51

BACKGROUND:Age-specific elevation in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, previously termed "heart stress (HS)," has been associated with adverse cardiovascular disease (CVD) outcomes. Yet, HS status, as defined by longitudinal changes in NT-proBNP concentrations, may improve risk assessment for CVD and mortality in older adults. OBJECTIVE:To evaluate HS status on the basis of 3-year changes in NT-proBNP concentrations with risk for total CVD and all-cause mortality in community-dwelling older adults free of prior CVD. DESIGN:Observational study. SETTING:The ASPREE (ASPirin in Reducing Events in the Elderly) trial and subsequent observational extension (ASPREE-XT). PARTICIPANTS:8454 participants (mean age, 78.0 years at year 3; 52.9% women) without prior CVD who had NT-proBNP measured at trial enrollment and year 3. MEASUREMENTS:Heart stress status, based on changes in NT-proBNP concentrations from enrollment to year 3, was examined in 4 categories: persistently HS-free, HS remission, incident HS, or sustained HS. The 2 coprimary outcomes were total CVD (nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or heart failure hospitalization) and all-cause mortality. RESULTS:Over a median follow-up of 8.0 years, 818 CVD events and 1584 deaths occurred. At year 8, compared with the persistently HS-free category, the adjusted absolute risks (ARs) for total CVD were increased by 7.4% (95% CI, 4.8% to 10.0%) for incident HS and 6.7% (CI, 4.3% to 9.0%) for sustained HS; adjusted ARs were also increased for all-cause mortality by 6.1% (CI, 3.7% to 8.5%) for incident HS and 7.5% (CI, 5.2% to 9.8%) for sustained HS. The HS remission category had similar adjusted ARs to those of the persistently HS-free group. LIMITATION:Observational design and predominantly White participants. CONCLUSION:Heart stress status based on longitudinal changes in NT-proBNP concentration may improve risk stratification of CVD and mortality. PRIMARY FUNDING SOURCE:None.

BACKGROUND:Functional decline may be an early indicator of dementia. This study examined the trajectories of frailty, grip strength, and gait speed over the 11 years prior to dementia, compared to matched individuals without dementia. METHODS:A total of 1092 dementia cases were matched on age, sex and education to 4368 controls from a cohort of community-dwelling older adults recruited in Australia and the USA, aged 65 years or above at recruitment. Frailty was characterised by a deficit-accumulation index involving 67 items. Hand grip strength and gait speed were measured regularly by physical examination. Linear mixed-effects models estimated the backward trajectories of frailty, grip strength and gait speed before dementia, compared to controls. Secondary analyses were stratified by sex and ApoE ε4 carrier status. RESULTS:Higher frailty burden, with a steeper increase over time, was found in the years before dementia, compared to controls (P-interaction < .001). Hand grip strength and gait speed declined more rapidly in dementia cases than in controls (P-interaction < .001 for both). Differences between cases and controls became consistently significant four to six years prior to dementia (P-contrast < .001). An earlier divergence across all three measures was observed for females, and to a lesser extent in ApoE ε4 non-carriers. DISCUSSION:Functional decline occurs within the decade before dementia onset, with gait speed being the earliest indicator. These findings support the utility of functional measures as early markers of dementia risk, with potential implications for targeted monitoring and preventative strategies.

Importance:The risk of cognitive decline and dementia following cardiovascular disease (CVD) events is well recognized. However, it remains unclear whether cognitive changes observed after such events reflect a process that begins prior to the event itself. Objective:To compare the cognitive trajectories of older adults preceding an incident CVD event with those of a matched control group without an event. Design, Setting, and Participants:Data for this nested case-control study were obtained from a prospective cohort of older, community-dwelling individuals (aged ≥65 years) in Australia and the US with no history of CVD at the time of study enrollment in the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial and the extension (ASPREE-XT) observational study. The ASPREE trial was conducted between March 2010 and December 2014, with follow-up to June 2017. The ongoing ASPREE-XT trial continued annual follow-up; this study reports data through December 2022. Case patients with an adjudicated CVD event, including fatal coronary heart disease (CHD), nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and hospitalization for heart failure (HHF), were matched by age, sex, and educational attainment to control participants without a CVD event. Data were analyzed from June to December 2024. Exposures:Cognitive function as assessed by the Modified Mini-Mental State Examination, the Hopkins Verbal Learning Test-Revised, the Symbol Digit Modalities Test, and the Controlled Oral Word Association Test. Main Outcomes and Measures:Linear mixed-effects models were used to estimate the trajectories of cognitive function among case patients with a CVD event and control participants. Results:Over 11 years, 1934 CVD events occurred among 19 114 participants. In this analysis, 1887 of 1934 case patients (97.6%) with adjudicated CVD events were matched to 7548 control participants (N = 9435; overall median age, 75.7 years [IQR, 72.4-80.0 years]; 4970 males [52.7%]). Individuals with incident CVD events had lower cognitive function, starting at between 3 and 8 years before the event, compared with those without CVD. Faster declines in global cognition (β, -0.19 [95% CI, -0.33 to -0.06]), episodic memory (β, -0.04 [-0.11 to -0.03]), processing speed (β, -0.28 [95% CI, -0.48 to -0.07]), and verbal fluency (β, -0.15 [95% CI, -0.27 to -0.04]) in the years prior to the CVD event were also observed compared with control participants. Composite global cognition (β, -0.11 [95% CI, -0.17 to -0.06]) and executive function scores (β, -0.07 [95% CI, -0.11 to -0.03]), but not memory, also declined faster. Similar cognitive trajectories were observed for fatal CHD, stroke, and HHF; however, this pattern was not observed for nonfatal MI, in which case patients and control participants showed comparable trends. Conclusions and Relevance:In this case-control study of community-dwelling older adults, deterioration in cognitive function was prominent prior to CVD events, suggesting that this decline may be associated with subsequent CVD events. These findings may help inform future research aimed at understanding the association between cognitive change and CVD.

BACKGROUND:Health-related quality of life is central to healthy ageing, yet gender differences among older adults and their underlying determinants are not well understood. We examined gender differences in quality of life in a large cohort of older Australians and the extent to which biopsychosocial factors mediate these differences. METHODS:We analysed baseline cross-sectional data from the Statins in Reducing Events in the Elderly trial, a randomised controlled trial of community-dwelling Australians aged ≥70 years without cardiovascular disease, major physical disability, or dementia. Quality of life was measured across eight domains of the 36-Item Short Form and summarised using the SF-6D index. Gender differences were examined using age-adjusted linear regression, with mediation assessed by the percentage reduction in the association between gender and quality of life after adjusting for individual biopsychosocial factors. RESULTS:Among 9971 participants (52% women; mean age 74.7 ± 4.5 years), women scored lower than men in Physical Functioning, Vitality, Mental Health, and Bodily Pain (all p < 0.001), but higher in General Health (p < 0.001). The SF-6D index was lower in women (mean difference - 0.03, p < 0.001). Pain severity, depressive symptoms, and histories of osteoarthritis and depression mediated the greatest amount of the gender difference in scores (between 42% and 92%). CONCLUSIONS:Older women reported better general health but poorer quality of life than men in most domains. These gender differences were largely attributable to pain and depressive symptoms, both of which are common and modifiable. Targeted management of these symptoms may improve quality of life and reduce gender disparities in later life.

Abstract BACKGROUND Though evidence indicates that treating hearing loss with hearing aids (HAs) could reduce dementia risk, the effects on biomarkers of Alzheimer's disease and related dementias (ADRD) remain unknown. METHODS Observational data from Aspirin in Reducing Events in the Elderly (ASPREE) study participants without dementia and with hearing problems were used. We emulated two target trials to estimate the effect of (1) new HA prescription and (2) the frequency of HA use on plasma ADRD biomarkers after 7 years using targeted maximum likelihood estimation, with multiple imputation for missing data. RESULTS There was a median of 2842 individuals (mean 75 years, 48% female) across imputed datasets, and 735 new HA prescriptions. Estimated treatment effects were close to null for phosphorylated tau181, neurofilament light chain, glial fibrillary acidic protein, and amyloid beta 42/40. There was little evidence of effect modification (e.g., by apolipoprotein E ε4 genotype). DISCUSSION In older people with hearing loss, HA prescription and frequency of use had minimal association with levels of ADRD biomarkers.

BACKGROUND:The effectiveness and safety of statins for the primary prevention of cardiovascular events and the extension of disability-free survival among older adults remain uncertain. METHODS:We conducted a double-blind, randomized, placebo-controlled trial at general medical practices across Australia. Community-dwelling adults at least 70 years of age with no history of cardiovascular disease, diabetes, or dementia were randomly assigned in a 1:1 ratio to receive atorvastatin at a dose of 40 mg once daily or identical placebo. The two primary end points were a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke, or coronary revascularization (to assess effects on major cardiovascular events) and a composite of death from any cause, dementia, or persistent physical disability (to assess effects on disability-free survival). Analyses were performed according to a hierarchical testing plan. RESULTS:A total of 9971 participants were enrolled: 4984 were assigned to receive atorvastatin and 4987 to receive placebo. The mean (±SD) age of the participants was 74.7±4.5 years, and 51.9% were women. After a median of 5.9 years, a primary cardiovascular event had occurred in 297 participants (10.9 events per 1000 person-years) in the atorvastatin group and in 412 participants (15.5 events per 1000 person-years) in the placebo group (hazard ratio, 0.70; 95% confidence interval [CI], 0.61 to 0.82; P<0.001). Death from any cause, dementia, or persistent physical disability occurred in 637 participants (21.6 events per 1000 person-years) in the atorvastatin group and in 676 participants (23.0 events per 1000 person-years) in the placebo group (hazard ratio, 0.94; 95% CI, 0.84 to 1.05; P = 0.25). Serious adverse events occurred in 131 participants (2.7%) in the atorvastatin group and in 129 (2.7%) in the placebo group, with musculoskeletal, hepatobiliary, and diabetes-related adverse events occurring more commonly in the atorvastatin group. CONCLUSIONS:Treatment with atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival among community-dwelling older adults without clinical cardiovascular disease. (Funded by the National Health and Medical Research Council and others; STAREE ClinicalTrials.gov number, NCT02099123.).

We investigated the association between physical activity (PA) intensity and dementia and cognitive decline in Australian community-dwelling older adults. This prospective cohort study uses data from 11,655 older adults (mean age (standard deviation, SD) = 75.0 (4.2) years, 53.4

Background This study aims to quantify transition probabilities between frailty states (not-frail, pre-frail, frail) and from different frailty states to the occurrence of a cardiovascular disease (CVD) event; and to examine how age, sex and sociodemographic factors influence these transitions. Methods 18,077 initially healthy individuals (91% Caucasians, 56% females) aged ≥65 years enrolled in the ASPREE study who had no prior CVD event and ADL (Activity of Daily Living) disability at recruitment were followed for a median of 7.4 years. Frailty was annually assessed using a 64-item Frailty Index. Continuous-time multi-state Markov modelling was used. Results The estimated transition probabilities from frail to CVD increased over time (11% at five years, and 18% at ten years) and consistently exceeded the corresponding five- and ten-year transition probabilities from pre-frail to CVD (8% and 14% respectively). Compared to males, females had a 26% higher relative risk of progressing to a pre-frail/frail state; however, they had about 50% lower relative risk of transitioning from pre-frail/frail to CVD. Older age, socioeconomic and geographic disparities were associated with up to 38% higher relative risk of worsening frailty and progression to CVD. Similar findings were observed when using the Fried phenotype. Conclusion The probability of transiting from pre-frail/frail to CVD increased over time, even among initially healthy older people. Targeted prevention strategies may be helpful to delay frailty progression and reduce CVD risk in older age, particularly socioeconomically disadvantaged individuals or those residing outside major cities, and different approaches may be required in females and males.

Although the importance of body weight in later life for brain health has been established, less is known about body shape and composition. This study aims to examine their associations with dementia and cognitive changes in older adults. Data were obtained from over 17,000 community-dwelling individuals aged 65-98 years, recruited in Australia and the US. We assessed body shape using the ratio of waist circumference to body mass index (WBR), and estimated lean (LM) and fat mass (FM) by the Hume formula. Dementia diagnosis was adjudicated according to DSM-IV. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed annually for 11 years. Cox regression and mixed-effects models were used respectively, to estimate the associations with incident dementia and cognitive changes over time. A higher WBR was associated with higher dementia risk in men (HR: 1.41, 95% CI: 1.04-1.93, p = 0.03), and with greater decline in all cognitive tests in both genders (coefficients: -0.123 to -0.030, all p-values<0.05). Conversely, lower dementia risk was shown in greater LM (men, HR: 0.97, 95% CI: 0.95-0.99, p<0.001; women, HR: 0.96, 95% CI: 0.95-0.98, p<0.001) and FM (men, HR: 0.62, 95% CI: 0.48-0.80, p<0.001; women, HR: 0.63, 95% CI: 0.49-0.81, p<0.001). Also, they showed slower decline in global cognition, episodic memory, and psychomotor speed (coefficients: 0.002 to 0.007, all p-values<0.05). Higher body weight in later life, independent of composition, may benefit brain health. However, increased abdominal fat poses risks for cognitive impairments.

OBJECTIVE:To examine the prevalence of health risk factors by rurality status and the association of rurality and incidence of disability-free survival (DFS), its components (death, dementia and physical disability), cardiovascular disease (CVD), cancer and underlying cause of death. METHODS:Data came from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and observational extension, ASPREE-XT. Community-dwelling Australians aged 70 years or older, with no prior CVD events, dementia or independence-limiting physical disability, were recruited through General Practitioners between 2010 and 2014. Area of residence was classified as major cities, inner regional or outer regional/remote. Major incident health events were adjudicated by expert panels. RESULTS:Participants (n = 16,697, median age 74 years; 55% female) were followed over a median 8.3 years. A small, but statistically significant higher prevalence of many health risk factors was found for individuals living outside metropolitan areas. Rurality was not associated with the incidence of DFS, dementia, physical disability or CVD events in adjusted Cox proportional hazards regression models. Compared to major cities, individuals in outer regions/remote areas had an increased risk of all-cause death (HR: 1.17; 95% CI 1.02, 1.34) which appeared to be driven by fatal CVD (HR: 1.40; 95% CI 1.02, 1.83), while those in inner regions had a lower cancer incidence (HR: .89; 95% CI .82, .98). CONCLUSIONS:Incidence of DFS, dementia and physical disability did not differ according to rurality. Heightened risk of mortality was evident outside urban areas, possibly reflecting inequitable health service and access. Lower cancer incidence in inner regions requires further investigation.