Publications by authors named "Anne M Murray"

74 Publications

Genomic Risk Prediction for Breast Cancer in Older Women.

Cancers (Basel) 2021 Jul 14;13(14). Epub 2021 Jul 14.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia.

Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40-69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3-1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2-1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2-3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56-0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59-0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.
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http://dx.doi.org/10.3390/cancers13143533DOI Listing
July 2021

Health-related quality of life and incident cardiovascular disease events in community-dwelling older people: A prospective cohort study.

Int J Cardiol 2021 Jul 7. Epub 2021 Jul 7.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia; Department of Epidemiology, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands. Electronic address:

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older individuals.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.004DOI Listing
July 2021

Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.

J Am Heart Assoc 2021 Jul 26;10(13):e019613. Epub 2021 Jun 26.

Berman Center for Outcomes and Clinical Research Hennepin-Health Research InstituteHennepin Healthcare Minneapolis MN.

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction =0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.
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http://dx.doi.org/10.1161/JAHA.120.019613DOI Listing
July 2021

Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population.

Aging Cell 2021 06 26;20(6):e13384. Epub 2021 May 26.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia.

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all-cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants. During a median 4.5 years of follow-up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased dementia risk and 1.4/1.8-fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4-fold dementia risk versus low (CI 1.04-1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96-1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.
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http://dx.doi.org/10.1111/acel.13384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208779PMC
June 2021

Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.

Alzheimers Dement (Amst) 2021 2;13(1):e12180. Epub 2021 May 2.

School of Public Health and Preventive Medicine Monash University Melbourne Australia.

Introduction: This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Methods: Generally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group-based trajectory modeling identified distinct cognitive trajectories.

Results: Four to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower-functioning trajectories ( < .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).

Discussion: Inter-individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.
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http://dx.doi.org/10.1002/dad2.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088593PMC
May 2021

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia.

J Alzheimers Dis 2021 ;80(2):895-904

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

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.
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http://dx.doi.org/10.3233/JAD-201349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093030PMC
January 2021

Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial.

Mol Psychiatry 2021 Jan 27. Epub 2021 Jan 27.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.

Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (-0.7; 95% CI -1.4 to -0.1; χ (1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.
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http://dx.doi.org/10.1038/s41380-021-01020-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313623PMC
January 2021

Health-related quality of life and all-cause mortality among older healthy individuals in Australia and the United States: a prospective cohort study.

Qual Life Res 2021 Apr 3;30(4):1037-1048. Epub 2021 Jan 3.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.

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.
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http://dx.doi.org/10.1007/s11136-020-02723-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005489PMC
April 2021

Effect of Aspirin on Activities of Daily Living Disability in Community-Dwelling Older Adults.

J Gerontol A Biol Sci Med Sci 2020 Dec 26. Epub 2020 Dec 26.

Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, U.S.

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 100mg aspirin versus placebo recruited 19,114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the U.S. Six basic ADLs were assessed every six months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after six months. Proportional hazards modelling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.

Results: Over a median 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 versus 5.3 events/1000py; HR=0.81, 95% 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 versus 12).

Discussion: Low-dose aspirin in initially healthy older people did not reduce risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.
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http://dx.doi.org/10.1093/gerona/glaa316DOI Listing
December 2020

Normative Data for the Symbol Digit Modalities Test in Older White Australians and Americans, African-Americans, and Hispanic/Latinos.

J Alzheimers Dis Rep 2020 Aug 4;4(1):313-323. Epub 2020 Aug 4.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Background: Processing speed, which can be assessed using the Symbol Digit Modalities Test (SDMT), is central to many brain functions. Processing speed declines with advanced age but substantial impairments are indicative of brain injury or disease.

Objective: The purpose of this study was to provide SDMT normative data for older community-dwelling individuals in the U.S. and Australia.

Methods: The ASPREE trial recruited 19,114 relatively healthy older men and women in Australia and the U.S. from the general community. All participants were without a diagnosis of dementia and with a Modified Mini-Mental State examination score of 78 or more at enrolment. The SDMT was administered at baseline as part of a neuropsychological test battery.

Results: The median age of participants was 74 years (range 65-99), and 56% were women. The median years of education was 12. Ethno-racial differences in SDMT performance were observed and normative data were thus presented separately for 16,289 white Australians, 1,082 white Americans, 891 African-Americans, and 316 Hispanic/Latinos. There were consistent positive associations found between SDMT and education level, and negative associations between SDMT and age. Mean scores for women were consistently higher than men with the exception of Hispanic/Latinos aged ≥70 years.

Conclusion: This study provides comprehensive SDMT normative data for whites (Australian and U.S.), Hispanic/Latinos, and African-Americans, according to gender, age, and education level. These norms can be used clinically as reference standards to screen for cognitive impairments in older individuals.
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http://dx.doi.org/10.3233/ADR-200194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504980PMC
August 2020

Cerebral blood flow characteristics following hemodialysis initiation in older adults: A prospective longitudinal pilot study using arterial spin labeling imaging.

Neuroimage Clin 2020 15;28:102434. Epub 2020 Sep 15.

Hennepin HealthCare Research Institute, Hennepin Healthcare, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Geriatrics Division, Department of Medicine, Hennepin Healthcare, Minneapolis, MN USA.

Purpose: To investigate cerebral blood flow (CBF) characteristics before and after hemodialysis initiation and their longitudinal associations with global cognitive function in older adults.

Methods: A cohort of 17 older end-stage renal disease patients anticipating standard thrice-weekly hemodialysis and a group of 11 age- and sex-matched healthy control volunteers were recruited for brain perfusion imaging studies using arterial spin labeling. Hemodialysis patients participated in a prospective longitudinal study using brain magnetic resonance imaging and global cognitive assessment using the Modified Mini-Mental State Examination (3MS) at two time points: baseline, 2.9 ± 0.9 months before, and follow-up, 6.4 ± 2.4 months after hemodialysis initiation. Healthy controls were imaged once using the same protocol. CBF analyses were performed globally in grey and white matter and regionally in the hippocampus and orbitofrontal cortex. Covariate-adjusted linear mixed-effects models were used for statistical analyses (significance: p < 0.05; marginal significance: p < 0.1).

Results: At baseline, global and regional CBF was significantly higher in hemodialysis patients than in healthy controls. However, after approximately 6 months of hemodialysis, CBF declined substantially in hemodialysis patients, and became comparable to those in healthy controls. Specifically, in the hemodialysis patients, CBF declined non-significantly globally for grey and white matter and significantly regionally in the hippocampus and orbitofrontal cortex. Marginally significant associations were observed between 3MS scores and regional CBF measurements in the hippocampus and orbitofrontal cortex at baseline and follow-up, and between longitudinal changes.

Conclusion: The significant decline in CBF after hemodialysis initiation and the observed association between longitudinal changes in regional CBF and 3MS scores suggest that decreased brain perfusion may contribute to the observed cognitive decline.
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http://dx.doi.org/10.1016/j.nicl.2020.102434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522859PMC
June 2021

Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease.

Kidney Int 2021 02 10;99(2):466-474. Epub 2020 Sep 10.

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Nephrology, Monash Medical Centre, Monash Health, Melbourne, Victoria, Australia. Electronic address:

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.
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http://dx.doi.org/10.1016/j.kint.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957958PMC
February 2021

Effect of Aspirin on Cancer Incidence and Mortality in Older Adults.

J Natl Cancer Inst 2021 Mar;113(3):258-265

Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.

Methods: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records.

Results: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64).

Conclusions: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.
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http://dx.doi.org/10.1093/jnci/djaa114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936068PMC
March 2021

Cancer history and risk factors in healthy older people enrolling in the ASPREE clinical trial.

Contemp Clin Trials 2020 09 31;96:106095. Epub 2020 Jul 31.

Department of Epidemiology & Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, Australia. Electronic address:

Background: Cancer is a leading cause of death globally. Given the elevated risk of cancer with age and an ageing population, it is important to understand the changing burden of cancer in older populations. The ASPirin in Reducing Events in the Elderly (ASPREE) study randomised healthy older individuals to 100 mg aspirin or placebo, with clinical outcomes and disability-free survival endpoints. Detailed baseline data provides a rare opportunity to explore cancer burden in a uniquely healthy older population.

Methods: At study enrolment (2010-2014), self-reported personal cancer history, cancer type and cancer risk factor data were sought from 19,114 participants (Australia, n = 16,703; U.S., n = 2411). Eligible participants were healthy, free of major diseases and expected to survive 5 years.

Results: Nearly 20% of enrolling ASPREE participants reported a prior cancer diagnosis; 18% of women and 22% of men, with women diagnosed younger (16% vs 6% of diagnoses <50 years). Cancer prevalence increased with age. Prevalence of prostate and breast cancer history were higher in U.S. participants; melanoma and colorectal cancer were higher in Australian participants. Cancer history prevalence was not associated with contemporary common risk factors nor previous aspirin use, but was associated with poor health ratings in men. Blood and breast cancer history were more common with past aspirin use.

Conclusions: Personal cancer history in healthy older ASPREE participants was as expected for the most common cancer types in the respective populations, but was not necessarily aligned with known risk factors. We attribute this to survivor bias, likely driven by entry criteria.

Trial Registration: International Standard Randomised Controlled Trial Number Register (ISRCTN83772183) and clinicaltrials.gov (NCT01038583).
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http://dx.doi.org/10.1016/j.cct.2020.106095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009087PMC
September 2020

Cognitive impairment and associated risk factors in older adult hemodialysis patients: a cross-sectional survey.

Sci Rep 2020 07 27;10(1):12542. Epub 2020 Jul 27.

Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Disease, Beijing, 100853, China.

The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.
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http://dx.doi.org/10.1038/s41598-020-69482-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385128PMC
July 2020

Antihypertensive medication use and blood pressure control among treated older adults.

J Clin Hypertens (Greenwich) 2020 08 15;22(8):1406-1414. Epub 2020 Jul 15.

ASPREE Investigator Group listed at, www.ASPREE.org.

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.
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http://dx.doi.org/10.1111/jch.13934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901812PMC
August 2020

Association of Statin Use With Disability-Free Survival and Cardiovascular Disease Among Healthy Older Adults.

J Am Coll Cardiol 2020 07;76(1):17-27

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

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.
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http://dx.doi.org/10.1016/j.jacc.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967891PMC
July 2020

Medically actionable pathogenic variants in a population of 13,131 healthy elderly individuals.

Genet Med 2020 11 1;22(11):1883-1886. Epub 2020 Jul 1.

Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Purpose: To measure the prevalence of medically actionable pathogenic variants (PVs) among a population of healthy elderly individuals.

Methods: We used targeted sequencing to detect pathogenic or likely pathogenic variants in 55 genes associated with autosomal dominant medically actionable conditions, among a population of 13,131 individuals aged 70 or older (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Participants had no previous diagnosis or current symptoms of cardiovascular disease, physical disability or dementia, and no current diagnosis of life-threatening cancer. Variant curation followed American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) standards.

Results: One in 75 (1.3%) healthy elderly individuals carried a PV. This was lower than rates reported from population-based studies, which have ranged from 1.8% to 3.4%. We detected 20 PV carriers for Lynch syndrome (MSH6/MLH1/MSH2/PMS2) and 13 for familial hypercholesterolemia (LDLR/APOB/PCSK9). Among 7056 female participants, we detected 15 BRCA1/BRCA2 PV carriers (1 in 470 females). We detected 86 carriers of PVs in lower-penetrance genes associated with inherited cardiac disorders.

Conclusion: Medically actionable PVs are carried in a healthy elderly population. Our findings raise questions about the actionability of lower-penetrance genes, especially when PVs are detected in the absence of symptoms and/or family history of disease.
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http://dx.doi.org/10.1038/s41436-020-0881-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606791PMC
November 2020

Aspirin for Primary Prevention in Adults Older than 70 Years is Not Supported by High-Quality Trial Data and May Cause Harm.

Am J Med 2020 07;133(7):e389-e390

School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.

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http://dx.doi.org/10.1016/j.amjmed.2020.02.031DOI Listing
July 2020

Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population.

Clin Pharmacol Ther 2020 12 20;108(6):1289-1298. Epub 2020 Jul 20.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post hoc analysis of 13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrollment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease (CVD) end point, and composites of major adverse cardiovascular events (MACE) and ischemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P < 0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331-A and treatment group, for CVD (P = 0.65), MACE (P = 0.32), STROKE (P = 0.56), MHEM (P = 0.59), or ICB (P = 0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population.
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http://dx.doi.org/10.1002/cpt.1959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959328PMC
December 2020

Familial Hypercholesterolemia in a Healthy Elderly Population.

Circ Genom Precis Med 2020 08 10;13(4):e002938. Epub 2020 Jun 10.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (P.L., M.R., J.T., A.B., R.L.W., A.M.T., C.M.R., J.J.M.).

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http://dx.doi.org/10.1161/CIRCGEN.120.002938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442644PMC
August 2020

Effect of Aspirin vs Placebo on the Prevention of Depression in Older People: A Randomized Clinical Trial.

JAMA Psychiatry 2020 10;77(10):1012-1020

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Importance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.

Objective: To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults.

Design, Setting, And Participants: This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included.

Interventions: Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years.

Main Outcomes And Measures: The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale.

Results: Of the 19 114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79 886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. The incidence rate of new CES-D-10 scores of 8 or more was 70.4 events per 1000 person-years in the aspirin group and 69.1 in the placebo group (hazard ratio, 1.02 [95% CI, 0.96-1.08]; P = .54).

Conclusions And Relevance: Low-dose aspirin did not prevent depression in this large-scale study of otherwise healthy older adults.

Trial Registration: ClinicalTrials.gov Identifier: NCT01038583.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.1214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271558PMC
October 2020

Patterns of Association between Depressive Symptoms and Chronic Medical Morbidities in Older Adults.

J Am Geriatr Soc 2020 08 13;68(8):1834-1841. Epub 2020 May 13.

School of Medicine, IMPACT the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Deakin University, Geelong, Victoria, Australia.

Objectives: To investigate the association between depressive symptoms and several medical morbidities, and their combination, in a large older population.

Design: Cross-sectional study of baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

Setting: Multicentric study conducted in Australia and the United States.

Participants: A total of 19,110 older adults (mean age = 75 years [standard deviation = ±4.5]).

Measurements: Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D 10) scale. Medical morbidities were defined according to condition-specific methods. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to test associations before and after accounting for possible confounders.

Results: Depressive symptoms were significantly associated with obesity (OR = 1.19; 95% CI = 1.07-1.32), diabetes (OR = 1.22; 95% CI = 1.05-1.42), gastroesophageal reflux disease (GERD) (OR = 1.41; 95% CI = 1.28-1.57), metabolic syndrome (OR = 1.16; 95% CI = 1.03-1.29), osteoarthritis (OR = 1.41; 95% CI = 1.27-1.57), respiratory conditions (OR = 1.25; 95% CI = 1.10-1.42), history of cancer (OR = 1.19; 95% CI = 1.05-1.34), Parkinson's disease (OR = 2.56; 95% CI = 1.83-3.56), polypharmacy (OR = 1.60; 95% CI = 1.44-1.79), and multimorbidity (OR = 1.29; 95% CI = 1.12-1.49). No significant association was observed between depressive symptoms and hypertension, chronic kidney disease, dyslipidemia, and gout (P > .05). A significant dose-response relationship was evident between the number of medical comorbidities and the prevalence of depression (OR = 1.18; 95% CI = 1.13-1.22).

Conclusion: Late-life depressive symptoms are significantly associated with several medical morbidities, and there appears to be a cumulative effect of the number of somatic diseases on the prevalence of depression. These findings augment the evidence for a complex relationship between mental and physical health in an otherwise healthy older population and might guide clinicians toward early recognition of high-risk individuals. J Am Geriatr Soc 68:1834-1841, 2020.
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http://dx.doi.org/10.1111/jgs.16468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879564PMC
August 2020

The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action.

Cancer Epidemiol Biomarkers Prev 2020 07 5;29(7):1283-1289. Epub 2020 May 5.

Social & Scientific Systems, Durham, North Carolina.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357669PMC
July 2020

No Modulation of the Effect of Aspirin by Body Weight in Healthy Older Men and Women.

Circulation 2020 03 30;141(13):1110-1112. Epub 2020 Mar 30.

Department of Epidemiology & Preventive Medicine, Monash University, Melbourne VIC, Australia (R.L.W., G.P., R.W., M.R.N., C.M.R., J.E.L., S.G.O., J.J.M.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286412PMC
March 2020

Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline.

Neurology 2020 07 25;95(3):e320-e331. Epub 2020 Mar 25.

From the School of Public Health and Preventive Medicine (J.R., E.S., R.L.W., R.W., C.M.R., S.A.W., J.E.L., S.G.O., R.T., J.J.M.) and the Turner Institute for Brain and Mental Health (T.T.J.C.), Monash University, Melbourne, Australia; Berman Center for Outcomes and Clinical Research (A.M.M., B.K.), Hennepin Health Research Institute; Division of Geriatrics, Department of Medicine (A.M.M., B.K.), Hennepin Healthcare, Minneapolis, MN; School of Public Health (C.M.R.), Curtin University, Perth; Menzies Institute for Medical Research (M.R.N.), University of Tasmania, Hobart, Australia; Sticht Center on Aging and Alzheimer's Prevention, Section on Gerontology and Geriatric Medicine, Department of Internal Medicine (J.D.W.), Wake Forest School of Medicine, Winston-Salem, NC; Center for Aging and Population Health (A.B.N.), University of Pittsburgh, PA; Department of Pharmacy Practice and Science, College of Pharmacy, and the Department of Family Medicine, Carver College of Medicine (M.E.E.), University of Iowa, Iowa City; and Department of Family Medicine and Rush Alzheimer's Disease Center (R.C.S.), Rush University Medical Center, Chicago, IL.

Objective: To determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older individuals.

Methods: Aspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling individuals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1-100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test-Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia ("trigger") based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging-Alzheimer's Association criteria were used for AD and MCI subclassification.

Results: A total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.91-1.17), probable AD (HR, 0.96; 95% CI, 0.74-1.24), or MCI (HR, 1.12; 95% CI, 0.92-1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups.

Conclusions: There was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing.

Classification Of Evidence: This study provides Class II evidence that for healthy older individuals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline.

Clinicaltrialsgov Identifier: NCT01038583.
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http://dx.doi.org/10.1212/WNL.0000000000009277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455352PMC
July 2020

Normative performance of older individuals on the Hopkins Verbal Learning Test-Revised (HVLT-R) according to ethno-racial group, gender, age and education level.

Clin Neuropsychol 2021 Aug 26;35(6):1174-1190. Epub 2020 Feb 26.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: The Hopkins Verbal Learning Test-Revised (HVLT-R) provides a measure of verbal learning and memory. The aim of this study was to provide normative performance data on the HVLT-R for community-dwelling older individuals according to ethno-racial group, age, gender, and years of completed education, in Australia and the U.S.

Method: The ASPirin in Reducing Events in the Elderly (ASPREE) study recruited 19,114 generally healthy community dwelling individuals aged 70 years and over (65 years and over for U.S minorities), who were without a diagnosis of dementia and scored above 77 on the modified Mini-Mental State (3MS) examination. Included in the analysis presented here were 16,251 white Australians, and in the U.S. 1,082 white, 894 African American and 314 Hispanic/Latino individuals at baseline.

Results: Performance on each of the components of the HVLT-R (trials 1-3, total, learning, delayed recall, delayed recognition, percentage retention and recognition discrimination index [RDI]) differed by demographic variables. In country and ethno-racial stratified analyses, female gender, younger age and higher education were significantly associated with better total recall, delayed recall and RDI. Among white Australians these characteristics were also associated with better retention. Age, education and gender-specific reference values across ethno-racial categories were determined.

Conclusions: Ethno-racial, age, gender and education-stratified normative data from this large cohort of community-dwelling older individuals will serve as important reference standards in Australia and the U.S. to assess cognition in older individuals.
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http://dx.doi.org/10.1080/13854046.2020.1730444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483610PMC
August 2021

The association of antihypertensive use and depressive symptoms in a large older population with hypertension living in Australia and the United States: a cross-sectional study.

J Hum Hypertens 2020 11 30;34(11):787-794. Epub 2020 Jan 30.

School of Medicine, IMPACT Strategic Research Centre, Barwon Health, Deakin University, Geelong, VIC, Australia.

Cardiovascular drugs impact many pathways involved in depression pathophysiology and treatment. However, their distinct impact on mood is underrecognized and the literature is conflicting. Therefore, using a very large and well-characterised sample of older adults with hypertension, we aimed to investigate the prevalence of depressive symptoms in users of different antihypertensive classes. We analysed baseline data from 14,195 older individuals with hypertension enroled in a large clinical trial. Median age was 75 years. The association of antihypertensive use by class and depression prevalence, as measured by a validated depression scale, was determined using logistic regression models. Multivariable logistic models were implemented to account for important confounding factors. Our analyses showed a positive association between depressive symptoms and the use of beta blockers (BB) (OR: 1.37; 95% CI: 1.17-1.60, p < 0.01), compared with users of other antihypertensive classes. All other classes of antihypertensives (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers) were not significantly associated with depressive symptoms. In secondary analysis, this relationship was stronger for lipophilic (39%) and nonselective BB (52%) compared with hydrophilic (26%) and selective medications (31%), respectively. This study adds further evidence for a probable association between BB and depression in a large sample of older adults with hypertension and no history of cardiovascular disease or heart failure. These findings should regenerate interest and increase awareness of clinicians about the possible adverse effects of these medications in an otherwise healthy older population.
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http://dx.doi.org/10.1038/s41371-020-0303-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390661PMC
November 2020

The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly.

Nat Commun 2020 01 23;11(1):435. Epub 2020 Jan 23.

Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
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http://dx.doi.org/10.1038/s41467-019-14079-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978518PMC
January 2020

Factors Associated With Treatment and Control of Hypertension in a Healthy Elderly Population Free of Cardiovascular Disease: A Cross-sectional Study.

Am J Hypertens 2020 04;33(4):350-361

Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Background: Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both "untreated" and "treated but uncontrolled" high BP.

Methods: We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. "Controlled hypertension" was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control.

Results: Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to "treated but uncontrolled" BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US).

Conclusions: High levels of "untreated" and "treated but uncontrolled" BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population.

Clinical Trials Registration: NCT01038583.
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http://dx.doi.org/10.1093/ajh/hpz192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109352PMC
April 2020
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