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Background: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. Objective: To describe characteristics associated with participation in MYB. Methods: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55–77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. Results: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70–5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11–0.32). A family history of Alzheimer’s disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. Conclusion: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation.

Few studies have explored the impact of low back or lower limb pain severity on recurrent (≥2) falls in older adults.Investigate the association between the severity of low back or lower limb pain, and ≥2 falls or falls-related injuries.Community-dwelling Australian males and females in the ASPREE Longitudinal Study of Older Persons (ALSOP), aged ≥70 years. Self-reported, cross-sectional questionnaire data regarding number of falls and falls-related injuries in the last 12 months; and sites and severity of pain experienced on most days. Adjusted relative risks (RR) were estimated from multivariable Poisson regression models, for males and females separately.Of 14,892 ALSOP participants, 13% (n = 1983) reported ≥2 falls ('recurrent fallers') in the last 12 months. Males and females who reported severe low back, or severe lower limb pain on most days were more likely to report ≥2 falls in the last 12 months compared to those with mild pain (lower back: males RR = 1.70 and females RR = 1.5, p = 0.001; lower limb: males RR = 2.0, p 0.001 and females RR = 1.4, p = 0.003). Female recurrent fallers who reported severe low back (RR = 1.3, p = 0.029) or lower limb (RR = 1.2, p = 0.024) pain on most days were more likely to report a falls-related injury in the last 12 months compared to females with mild pain.Severe low back or lower limb pain was associated with an increased likelihood of recurrent falls (males/females) or falls-related injuries (females only). Assessment of severe low back and lower limb pain should be considered as a priority when undertaking falls-risk evaluation.Severe low back pain, or severe lower limb pain is associated with an increased likelihood of recurrent falls in older males and females, and an increased likelihood of falls-related injuries in older female recurrent fallers. Assessment and management of severe low back and lower limb pain should be prioritized when undertaking falls-risk assessment. Future longitudinal research is required to further interrogate this relationship and its underlying mechanisms.

Background: Impaired cerebral blood flow has been associated with an increased risk of falls. Mean arterial pressure (MAP) and variability in MAP have been reported to affect cerebral blood flow but their relationships to the risk of falls have not previously been reported. Methods: Utilising data from the Aspirin in Reducing Events in the Elderly trial participants, we estimated MAP and variability in MAP, defined as within-individual SD of MAP from baseline and first 2 annual visits. The relationship with MAP was studied in 16 703 participants amongst whom 1539 falls were recorded over 7.3 years. Variability in MAP was studied in 14 818 of these participants who experienced 974 falls over 4.1 years. Falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratio and 95% CI for associations with falls. Results: Long-term variability in MAP was not associated with falls except amongst frail or prefrail participants using antihypertensive medications. Within this group each 5 mm Hg increase in long-term variability in MAP increased the risk of falls by 16% (hazard ratio, 1.16 [95% CI, 1.02–1.33]). Amongst the antihypertensive drugs studied, beta-blocker monotherapy (hazard ratio, 1.93 [95% CI, 1.17–3.18]) was associated with an increased risk of falls compared with calcium channel blockers. Conclusions: Higher levels of long-term variability in MAP increase the risk of serious falls in older frail and prefrail individuals taking antihypertensive medications. The observation that the relationship was limited to frail and prefrail individuals might explain some of the variability of previous studies linking blood pressure indices and falls.

Prescribed opioids are commonly used in the older community-dwelling population for the treatment of chronic pain. Although the harmful effects of opioid abuse and overdose are well understood, little is known about the long-term cardiovascular (CV) effects of prescribed opioids. The aim of this study was to investigate the CV effects associated with prescribed opioid use.A post hoc analysis of participants in the Aspirin in Reducing Events in the Elderly (ASPREE) trial was conducted. Participants in the ASPREE trial included community-dwelling older adults without a prior history of CV disease (CVD). Prescribed opioid use was defined as opioid use at baseline and/or at the first annual visit (AV1). Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (95% CI) for associations between opioid use and CVD events following AV1. Of the 17 701 participants included (mean age 75.2 years, 58.2% female), 813 took opioids either at baseline or at AV1. Over a median follow-up period of 3.58 years (IQR 2.50-4.62), CVD events, most notably heart failure hospitalization, occurred in 7% (n = 57) amongst opioid users and 4% (n = 680) amongst non-opioid users. After adjustment for multiple covariates, opiate use was associated with a 1.67-fold (CI 1.26-2.23, P 0.001) increase in the hazard ratio for CVD events.These findings identify opioid use as a non-traditional risk factor for CVD events in community-dwelling older adults.

Supplementary Figure from Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts

Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals

MUTYH carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C>T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03–2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42–8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81–2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C>T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations.Prevention Relevance:Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.

Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the association between genetic susceptibility to colorectal cancer and aspirin use in a prospective study of 12,609 individuals of European descent ages ≥70 years, enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) double-blinded, placebo-controlled randomized trial (randomized controlled trial; RCT). Cox proportional hazards models were used to assess the association of aspirin use on colorectal cancer, as well as the interaction between the PRS and aspirin treatment on colorectal cancer. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident colorectal cancer. Aspirin assignment was not associated with incidence of colorectal cancer overall [HR = 0.94; 95% confidence interval (CI), 0.68–1.30] or within strata of PRS (P for interaction = 0.97). However, the PRS was associated with an increased risk of colorectal cancer (HR = 1.28 per SD; 95% CI, 1.09–1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR = 1.85; 95% CI, 1.08–3.15). In a prospective RCT of older individuals, a PRS is associated with incident colorectal cancer risk, but aspirin use was not associated with a reduction of incident colorectal cancer, regardless of baseline genetic risk.Prevention Relevance:There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older individuals outweighs the benefit. We sought to determine whether some older individuals might still benefit from aspirin based on their genetic susceptibility.

Background Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. Objective To evaluate disability-free survival (DFS) in older individuals by glycaemic status. Methods This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] Results We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21–1.60), all-cause mortality (1.45, 1.23–1.72), persistent physical disability (1.73, 1.35–2.22), CIND (1.22, 1.08–1.38), MACE (1.30, 1.04–1.63) and cardiovascular events (1.25, 1.02–1.54) but not dementia (1.13, 0.87–1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93–1.12) or other outcomes. Conclusions Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.

Background Unhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and premature mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their impact on the health of older people is less certain. Methods The study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with all-cause and cause-specific mortality. Results In multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality. Stratified analysis indicated larger effect sizes among males, those ≤ 73 years old and among those in the aspirin treatment group. Conclusions In a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality.

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI : 1.82; 95% CI 1.30–2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI : 1.64; 95% CI 1.26–2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.

BACKGROUND: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. METHODS: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. FINDINGS: 19 114 participants with a median age of 74·0 years (IQR 71·6-77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6-5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI 144-172) from cancer, 112 events per 1000 person-years (86-145) from stroke, 88 events per 1000 person-years (68-111) from cardiac disease, 69 events per 1000 person-years (58-82) from disability or dementia, and four events per 1000 person-years (4-5) from a healthy state. Age was significantly associated with an accelerated rate for most transitions. Male sex (vs female sex) was significantly associated with an accelerate rate for five of 12 transitions. INTERPRETATION: We describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. FUNDING: The National Institutes of Health.

Brain age is a neuroimaging-based biomarker of aging. This study examined whether the difference between brain age and chronological age (brain-PAD) is associated with cognitive function at baseline and longitudinally. Participants were relatively healthy, predominantly white community-dwelling older adults (n = 531, aged ≥70 years), with high educational attainment (61% ≥12 years) and socioeconomic status (59% ≥75th percentile). Brain age was estimated from T1-weighted magnetic resonance images using an algorithm by Cole et al., 2018. After controlling for age, gender, education, depression and body mass index, brain-PAD was negatively associated with psychomotor speed (Symbol Digit Modalities Test) at baseline (Bonferroni p < 0.006), but was not associated with baseline verbal fluency (Controlled Oral Word Association Test), delayed recall (Hopkins Learning Test Revised), or general cognitive status (Mini-Mental State Examination). Baseline brain-PAD was not associated with 3-year change in cognition (Bonferroni p > 0.006). These findings indicate that even in relatively healthy older people, accelerated brain aging is associated with worse psychomotor speed, but future longitudinal research into changes in brain-PAD is needed.

Identification of individuals with increased risk of major adverse cardiovascular events (MACE) is important. However, algorithms specific to the elderly are lacking. Data were analysed from a randomised trial involving 18,548 participants ≥ 70 years old (mean age 75.4 years), without prior cardiovascular disease events, dementia or physical disability. MACE included coronary heart disease death, fatal or nonfatal ischaemic stroke or myocardial infarction. Potential predictors tested were based on prior evidence and using a machine-learning approach. Cox regression analyses were used to calculate 5-year predicted risk, and discrimination evaluated from receiver operating characteristic curves. Calibration was also assessed, and the findings internally validated using bootstrapping. External validation was performed in 25,138 healthy, elderly individuals in the primary care environment. During median follow-up of 4.7 years, 594 MACE occurred. Predictors in the final model included age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, serum creatinine, diabetes and intake of antihypertensive agents. With variable selection based on machine-learning, age, sex and creatinine were the most important predictors. The final model resulted in an area under the curve (AUC) of 68.1 (95% confidence intervals 65.9; 70.4). The model had an AUC of 67.5 in internal and 64.2 in external validation. The model rank-ordered risk well but underestimated absolute risk in the external validation cohort. A model predicting incident MACE in healthy, elderly individuals includes well-recognised, potentially reversible risk factors and notably, renal function. Calibration would be necessary when used in other populations.

Background: Social health reflects one’s ability to form interpersonal relationships. Poor social health is a risk factor for cardiovascular disease (CVD), however an in-depth exploration of the link through CVD risk factors is lacking. Aim: To examine the relationship between social health (social isolation, social support, loneliness) and CVD risk factors among healthy older women and men. Methods: Data were from 11,498 healthy community-dwelling Australians aged ≥70 years from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Longitudinal Study of Older Persons sub-study. Ten-year CVD risk was estimated using the Atherosclerotic CVD Risk Scale (ASCVDRS) and the Framingham Risk Score (FRS). Results: Physical inactivity and experiencing depressive symptoms were the only CVD risk factors that consistently differed by all three social health constructs. Loneliness was associated with greater ASCVDRS (women: β = 0.01, p

Purpose: Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. Methods: This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. Results: Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00). Conclusion: There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.

OBJECTIVE: Optimism is modifiable and may be associated with healthy aging. We aim to investigate whether dispositional optimism is associated with all-cause mortality in adults 70 years and older. METHODS: Between 2010 and 2014, older adults free of serious cardiovascular disease and dementia were recruited through primary care physicians and enrolled in the Aspirin Reducing Events in the Elderly (ASPREE) clinical trial. Australian ASPREE participants were invited to participate in the ASPREE Longitudinal Study of Older Persons (ALSOP) that was running in parallel to ASPREE. Optimism was assessed at baseline using the Life Orientation Test-Revised. The association between optimism, divided into quartiles, and all-cause mortality was assessed using Cox proportional hazards models. RESULTS: A total of 11,701 participants (mean [standard deviation] age = 75.1 [4.24] years; 46.6% men) returned the ALSOP Social questionnaire and completed the Life Orientation Test-Revised. During a median follow-up of 4.7 years, 469 deaths occurred. The fully adjusted model was not significant (hazard ratio = 0.78, 95% confidence interval = 0.58-1.06). There was evidence that age was an effect modifier of the association between optimism and longevity. Higher optimism was associated with lower mortality risk in the oldest individuals only (77+ years; hazard ratio = 0.61, 95% confidence interval = 0.39-0.96). CONCLUSIONS: We observed no independent relationship between optimism and all-cause mortality in the total sample, although optimism seemed to be associated with lower risk among the oldest old (adults 77 years and older).

Background and Purpose: Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. Methods: We predicted risk of incident IS events in a population of 12 792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly). The PRS was calculated using 3.6 million genetic variants. Participants had no previous history of cardiovascular events, dementia, or persistent physical disability at enrollment. The primary outcome was IS over 5 years, with stroke subtypes as secondary outcomes. A multivariable model including conventional risk factors was applied and reevaluated after adding PRS. Area under the curve and net reclassification were evaluated. Results: At baseline, mean population age was 75 years. In total, 173 incident IS events occurred over a median follow-up of 4.7 years. When PRS was added to the multivariable model as a continuous variable, it was independently associated with IS (hazard ratio, 1.41 [95% CI, 1.20–1.65] per SD of the PRS; P P =0.004) compared with the lowest. The area under the curve of the conventional model was 66.6% (95% CI, 62.2–71.1) and after inclusion of the PRS, improved to 68.5 ([95% CI, 64.0–73.0] P =0.095). In subgroup analysis, the continuous PRS remained an independent predictor for large vessel and cardioembolic stroke subtypes but not for small vessel stroke. Reclassification was improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.17–0.43). Conclusions: PRS predicts incident IS in a healthy older population but only moderately improves prediction over conventional risk factors. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583.

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.

Choosing an antiplatelet strategy in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) at high bleeding risk (HBR), undergoing post-percutaneous coronary intervention (PCI), is complex. We used a unique open-source approach (crowdsourcing) to document if practices varied across a small, global cross-section of antiplatelet prescribers in the post-PCI setting.Five-hundred and fifty-nine professionals from 70 countries (the 'crowd') completed questionnaires containing single- or multi-option and free form questions regarding antiplatelet clinical practice in post-PCI NSTE-ACS patients at HBR. A threshold of 75% defined 'agreement'. There was strong agreement favouring monotherapy with either aspirin or a P2YThe crowdsourcing methodology showed potential as a tool to assess current practice and variation on a global scale and to achieve a broad demographic representation. These preliminary results indicate a high degree of variation with respect to duration of DAPT, monotherapy drug of choice following DAPT and how thrombotic and bleeding risk are assessed. Further investigations should concentrate on interrogating practice variation between key demographic groups.

Frailty and chronic kidney disease (CKD) both increase with age and are prevalent in older adults. However, studies in older adults examining the relationship between frailty and milder impairments of kidney function are relatively sparse. We examined the cross-sectional association of baseline estimated glomerular filtration rate (eGFR), albuminuria and CKD ([eGFR60 ml/min/1.73 m

MUTYH carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C>T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03–2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42–8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81–2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C>T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.

To assess the accuracy and precision of infrared cameras compared to traditional measures of temperature measurement in a temperature, humidity, and distance controlled intensive care unit (ICU) population. This was a prospective, observational methods comparison study in a single centre ICU in Metropolitan Melbourne, Australia. A convenience sample of 39 patients admitted to a single room equipped with two ceiling mounted thermal imaging cameras was assessed, comparing measured cutaneous facial temperature via thermal camera to clinical temperature standards. Uncorrected correlation of camera measurement to clinical standard in all cases was poor, with the maximum reported correlation 0.24 (Wide-angle Lens to Bladder temperature). Using the wide-angle lens, mean differences were − 11.1 °C (LoA − 14.68 to − 7.51), − 11.1 °C ( − 14.3 to − 7.9), and − 11.2 °C ( − 15.23 to − 7.19) for axillary, bladder, and oral comparisons respectively (Fig. 1a). With respect to the narrow-angle lens compared to the axillary, bladder and oral temperatures, mean differences were − 7.6 °C ( − 11.2 to − 4.0), − 7.5 °C ( − 12.1 to − 2.9), and − 7.9 °C ( − 11.6 to − 4.2) respectively. AUCs for the wide-angle lens and narrow-angle lens ranged from 0.53 to 0.70 and 0.59 to 0.79 respectively, with axillary temperature demonstrating the greatest values. Infrared thermography is a poor predictor of patient temperature as measured by existing clinical standards. It has a moderate ability to discriminate fever. It is unclear if this would be sensitive enough for infection screening purposes.Fig. 1Bland–Altman plots for temperatures measured using clinical standards to infrared camera. a Wide-angle camera versus bladder temperature. b Narrow-angle camera versus bladder temperature Supplementary Information The online version contains supplementary material available at 10.1007/s10877-021-00731-y.

Genetic testing is used to optimise the management of inherited cardiovascular disorders that can cause sudden cardiac death. Yet more genotype–phenotype correlation studies from populations not ascertained on clinical symptoms or family history of disease are required to improve understanding of gene penetrance. We performed targeted sequencing of 25 genes used routinely in clinical genetic testing for inherited cardiovascular disorders in a population of 13,131 asymptomatic older individuals (mean age 75 years) enrolled in the ASPREE trial. Participants had no prior history of cardiovascular disease events, dementia or physical disability at enrolment. Variants were classified following ACMG/AMP standards. Sudden and rapid cardiac deaths were clinically adjudicated as ASPREE trial endpoints, and assessed during mean 4.7 years of follow-up. In total, 119 participants had pathogenic/deleterious variants in one of the 25 genes analysed (carrier rate of 1 in 110 or 0.9%). Participants carried variants associated with hypertrophic cardiomyopathy (N = 24), dilated cardiomyopathy (N = 29), arrhythmogenic right-ventricular cardiomyopathy (N = 22), catecholaminergic polymorphic ventricular tachycardia (N = 4), aortopathies (N = 1), and long-QT syndrome (N = 39). Among 119 carriers, two died from presumed sudden/rapid cardiac deaths during follow-up (1.7%); both with pathogenic variants in long-QT syndrome genes (KCNQ1, SCN5A). Among non-carriers, the rate of sudden/rapid cardiac deaths was significantly lower (0.08%, 11/12936, p

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 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.