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INTRODUCTION: This study investigated whether epigenetic age acceleration (AA) is associated with the change in cognitive function and the risk of incident dementia over 9 years, separately in males and females. METHODS: Six epigenetic AA measures, including GrimAge, were estimated in baseline blood samples from 560 Australians aged ≥70 years (50.7% female). Cognitive assessments included global function, episodic memory, executive function, and psychomotor speed. Composite cognitive scores were also generated. Dementia (Diagnostic and Statistical Manual for Mental Disorders – IV [DSM‐IV] criteria) was adjudicated by international experts. RESULTS: Associations between epigenetic AA and cognitive performance over‐time varied by sex. In females only, GrimAA/Grim2AA was associated with worse delayed recall, composite cognition, and composite memory (adjusted‐beta ranged from –0.1372 to –0.2034). In males only, GrimAA/Grim2AA was associated with slower processing speed (adjusted‐beta, –0.3049) and increased dementia risk (adjusted hazard ratios [HRs], 1.78 and 2.00, respectively). DISCUSSION: Epigenetic AA is associated with cognitive deterioration in later life but with evidence of sex‐specific associations. Highlights: Epigenetic age acceleration was associated with cognitive deterioration over time.However, these associations differed by sex.In females, accelerated GrimAge appeared to be a better marker of decline in memory.In males, accelerated GrimAge was associated with slower processing speed over time.Association between accelerated GrimAge and dementia risk was found only in males. [ABSTRACT FROM AUTHOR]

Background Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years. Methods Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate. Results Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P  < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P  < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability. Conclusion Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty. [ABSTRACT FROM AUTHOR]

Females live longer than males, and there are sex disparities in physical health and disease incidence. However, sex differences in biological aging have not been consistently reported and may differ depending on the measure used. This study aimed to determine the correlations between epigenetic age acceleration (AA), and other markers of biological aging, separately in males and females. We additionally explored the extent to which these AA measures differed according to socioeconomic characteristics, clinical markers, and diseases. Epigenetic clocks (HorvathAge, HannumAge, PhenoAge, GrimAge, GrimAge2, and DunedinPACE) were estimated in blood from 560 relatively healthy Australians aged ≥ 70 years (females, 50.7%) enrolled in the ASPREE study. A system-wide deficit accumulation frailty index (FI) composed of 67 health-related measures was generated. Brain age and subsequently brain-predicted age difference (brain-PAD) were estimated from neuroimaging. Females had significantly reduced AA than males, but higher FI, and there was no difference in brain-PAD. FI had the strongest correlation with DunedinPACE (range r: 0.21 to 0.24 in both sexes). Brain-PAD was not correlated with any biological aging measures. Significant correlations between AA and sociodemographic characteristics and health markers were more commonly found in females (e.g., for DunedinPACE and systolic blood pressure r = 0.2, p < 0.001) than in males. GrimAA and Grim2AA were significantly associated with obesity and depression in females, while in males, hypertension, diabetes, and chronic kidney disease were associated with these clocks, as well as DunedinPACE. Our findings highlight the importance of considering sex differences when investigating the link between biological age and clinical measures. [ABSTRACT FROM AUTHOR]

Lower health-related quality of life (HRQoL) has been shown to predict a higher risk of hospital readmission and mortality in patients with cardiovascular disease (CVD). Few studies have explored the associations between HRQoL and incident CVD. We explored the associations between baseline HRQoL and incident and fatal CVD in community-dwelling older people in Australia and the United States. Longitudinal study using ASPirin in Reducing Events in the Elderly (ASPREE) trial data. This includes 19,106 individuals aged 65–98 years, initially free of CVD, dementia, or disability, and followed between March 2010 and June 2017. The physical (PCS) and mental component scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Incident major adverse CVD events included fatal CVD (death due to atherothrombotic CVD), hospitalizations for heart failure, myocardial infarction or stroke. Analyses were performed using Cox proportional-hazard regression. Over a median 4.7 follow-up years, there were 922 incident CVD events, 203 fatal CVD events, 171 hospitalizations for heart failure, 355 fatal or nonfatal myocardial infarction and 403 fatal or nonfatal strokes. After adjustment for sociodemographic, health-related behaviours and clinical measures, a 10-unit higher PCS, but not MCS, was associated with a 14% lower risk of incident CVD, 28% lower risk of hospitalization for heart failure and 15% lower risk of myocardial infarction. Neither PCS nor MCS was associated with fatal CVD events or stroke. Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older individuals. • Our study provides some of the first evidence that health-related quality of life (HRQoL) is associated with incident CVD. • Lower physical HRQoL is associated with a high CVD risk in relatively healthy older people. • Physical HRQoL can be used in combination with clinical information to evaluate incident CVD risk among older people. [ABSTRACT FROM AUTHOR]

Purpose: Previous research has demonstrated that lower health-related quality of life (HRQoL) is associated with higher morbidity and mortality, especially in-patient groups. The association of HRQoL with all-cause mortality in community samples requires further investigation. This study aimed to examine whether HRQoL predicts all-cause mortality in older healthy community-dwelling people from Australia and the United States (U.S.) enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial. We also explored whether this association varies by gender or country. Method: A prospective cohort of 19,106 individuals aged 65–98 years, who were without a dementia diagnosis or a known major life-limiting disease, and completed the 12-item short-form-HRQoL at recruitment (2010–2014). They were followed until June 2017. Cox proportional-hazard models were used to determine the association between the physical (PCS) and mental component scores (MCS) of HRQoL and all-cause mortality, adjusting for sociodemographic factors, health-related behaviours and clinical measures. Hazards ratios were estimated for every 10-unit increase in PCS or MCS. Results: There were 1052 deaths over a median 4.7-years (interquartile range 3.6–5.7) of follow-up, with 11.9 events per 1000 person-years. Higher PCS was associated with lower all-cause mortality (HR 0.83, 95% CI 0.77, 0.89) in the entire sample, while higher MCS was associated with lower mortality among U.S. participants only (HR 0.78, 95% CI 0.63, 0.95). Gender differences in the association of either PCS or MCS with mortality were not observed. Conclusion: Our large study provides evidence that HRQoL is inversely associated with all-cause mortality among initially healthy older people. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population.Objective: We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences.Methods: 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65-98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010-2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively.Results: At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender.Conclusion: Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling older people. [ABSTRACT FROM AUTHOR]

Background Health-related quality of life (HRQoL) is a measure of an individual's self-perceived health status. Few studies have examined HRQoL as a risk factor for mortality. This study examined whether HRQoL predicts all-cause mortality in older community-dwelling individuals from Australia and the United States enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial, and if this association varies across gender. Methods The 19,106 persons aged 65–98 years and free of known major life-limiting disease, who completed the 12-item short form (SF-12) HRQoL at ASPREE-baseline (2010–2014) were followed prospectively until 2017 for all-cause mortality. Cox proportional-hazard models were used to determine the association between the physical (PCS) and mental component scores (MCS) of HRQoL and all-cause mortality, adjusting for sociodemographic factors, health-related behaviours, and clinical measures. Results There were 1,052 deaths over a median 4.7-year of follow-up, with 11.9 events per 1,000 person-years. A 10-unit increase in PCS was associated with a 17% decrease in all-cause mortality (95%CI: 0.77, 0.89). MCS was not associated with all-cause mortality. There was no evidence these associations were different between males and females (P-values for interaction: PCS 0.13 and MCS 0.44). Conclusions PCS, but not MCS, was inversely associated with all-cause mortality in this large cohort of healthy older individuals. Key messages Our findings support the decision of the Australian Commission on Safety and Quality in Health Care to incorporate the SF-12 into the routine collection of Patient Reported Outcome Measures as a policy goal for the Australian health system. [ABSTRACT FROM AUTHOR]