Publications by authors named "John McNeil"

Elevated fasting insulin levels (FI), indicative of altered insulin secretion and sensitivity, may precede type 2 diabetes (T2D) and cardiovascular disease onset. In this study, we group FI-associated genetic variants based on their genetic and phenotypic similarities and identify seven clusters with distinct mechanisms contributing to elevated FI levels. Clusters fall into two types: "non-diabetogenic hyperinsulinemia," where clusters are not associated with increased T2D risk, and "diabetogenic hyperinsulinemia," where T2D associations are driven by body fat distribution, liver function, circulating lipids, or inflammation.

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Objective: Whether blood sex hormone concentrations predict cognitive decline and incident dementia in older women is uncertain. The Sex Hormones in Older Women (SHOW) study is a prospective cohort study of Australian women, aged at least 70 years, without cognitive impairment.

Methods: Sex hormones were measured by liquid chromatography-tandem mass spectrometry, and comprehensive cognitive testing was performed at baseline and 3 years later.

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Background Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample.

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Background: Testosterone has been implicated in mood regulation, yet its role in the development and treatment of depression remains unclear. This study investigated the association between testosterone concentrations and the incidence of depression in older men.

Methods: We utilized data from 4,107 men aged 70 years and older who participated in the Aspirin in Reducing Events in the Elderly (ASPREE) and ASPREE-XT studies.

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Background And Objectives: Lipid metabolism in older adults is affected by various factors including biological aging, functional decline, reduced physiologic reserve, and nutrient intake. The dysregulation of lipid metabolism could adversely affect brain health. This study investigated the association between year-to-year intraindividual lipid variability and subsequent risk of cognitive decline and dementia in community-dwelling older adults.

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Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors.

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Background/objectives: Egg consumption in adults has been linked with a modestly increased risk of all-cause and CVD mortality. However, evidence on adults aged 65 y+ is limited. The objective of this study was to investigate the association between egg intake and mortality in community-dwelling older adults.

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Objective: To examine whether low circulating sex steroid concentrations are associated with the incidence of knee and hip replacement for osteoarthritis in community-dwelling older women.

Study Design: This prospective cohort study examined 5535 Australian women recruited into the Aspirin in Reducing Events in the Elderly (ASPREE) trial, aged ≥70 years, not taking medications affecting sex steroid concentrations, and with sex steroid concentrations measured by liquid chromatography-tandem mass spectrometry.

Main Outcome Measures: The incidence of knee and hip replacement for osteoarthritis was determined by hospitalisations for knee and hip surgical procedures where osteoarthritis was recorded as the indication.

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Article Synopsis
  • - The study investigated how levels of sex hormone binding globulin (SHBG) relate to fracture risk in older women, focusing on a group of 4,871 women aged 70 and above who weren't on specific medications.
  • - Results showed a positive correlation between higher SHBG levels and increased fracture risk over approximately 3.9 years, with those in the highest SHBG quartile being significantly more at risk compared to the lowest quartile.
  • - Although two genetic variants were found to influence SHBG levels, they did not correlate with fracture risk, indicating that the increased fracture risk associated with SHBG was not due to genetic factors.
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The impact of metabolic dysfunction-associated steatotic liver disease (MASLD), the preferred nomenclature for NAFLD, on cardiovascular health and mortality among older adults is uncertain. As such, we aimed to identify whether MASLD increases the risk of Major Adverse Cardiovascular Events (MACE) (a composite of fatal coronary heart disease [excluding heart failure], nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke), Atrial Fibrillation (AF), or all-cause mortality in older adults, and whether aspirin attenuates these risks in individuals with MASLD. This is a non-prespecified post-hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial.

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Introduction: Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community-dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle, or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing handicap.

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Objectives: To examine changes in out-of-hospital cardiac arrest (OHCA) characteristics and outcomes during 2003-2022, and 12-month outcomes for people who experienced OHCA during 1 January 2010 - 30 June 2022.

Study Design: Retrospective observational study; analysis of Victorian Ambulance Cardiac Arrest Registry (VACAR) data.

Setting, Participants: OHCA events in Victoria not witnessed by emergency medical services personnel, 1 January 2003 - 31 December 2022.

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Objectives: The relationship between nut intake and disability-free survival (healthy lifespan) in later life is unclear. The objective was to evaluate the association between nut intake and disability-free survival in a cohort of adults aged ≥70 years, and whether this varied according to overall diet quality.

Methods: This prospective cohort study involved 9916 participants from the ASPREE Longitudinal Study of Older Persons.

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Background: The risk-benefit balance of statin use in healthy older people is uncertain. We describe the baseline characteristics of the STAREE (Statins in Reducing Events in the Elderly) trial, which is a randomized, double-blind, placebo-controlled trial among community-dwelling older people; the trial evaluated the effect of atorvastatin 40 mg for the prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke), and on disability-free survival (survival free of both dementia and persistent physical disability).

Methods And Results: STAREE enrolled people aged ≥70 years from 1583 general practices across Australia with no history of clinical cardiovascular disease, diabetes, or dementia.

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Article Synopsis
  • Recent trials show that aspirin for preventing heart disease often leads to more bleeding risks than benefits, particularly in the general population.
  • This study analyzed data from the ASPREE trial, focusing on individuals with a high genetic risk for coronary artery disease (CAD).
  • Findings revealed that those in the highest genetic risk group experienced a significant reduction in CAD events with aspirin, without increased bleeding risk, suggesting aspirin may be beneficial for high-risk individuals.
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Objectives: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over.

Methods: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses.

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Objective: Conduct a systematic review and meta-analysis of the efficacy of therapeutic plasma exchange (TPE) or intravenous cangrelor to prevent thromboembolism in patients with heparin-induced thrombocytopenia (HIT) who undergo cardiopulmonary bypass (CPB) with heparin.

Design: Systematic review and meta-analysis.

Setting: N/A.

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Article Synopsis
  • The study explored how slow gait speed and weak handgrip strength in older adults are linked to an increased risk of developing depression over time.
  • It utilized data from a large group of participants (17,231) over approximately 4 years, measuring depression through a validated self-reported scale.
  • Findings indicate that both low physical performance measures are significant risk factors for depression, suggesting the importance of addressing physical health to improve mental well-being in older adults.
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Article Synopsis
  • The study investigates the potential link between obstructive sleep apnea (OSA) and cerebral small vessel disease (CSVD), which may contribute to dementia risk, focusing on how aspirin affects these factors in older adults over three years.
  • Participants aged 70 and above without major health issues underwent sleep studies, and their brain health was assessed using MRI to measure white matter hyperintensities and silent brain infarctions.
  • Findings revealed that OSA was common among participants, but it did not show a relationship with changes in brain imaging measures or retinal vessel sizes, and aspirin use did not significantly alter these outcomes.
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Purpose Of Review: Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial.

Recent Findings: Evidence of Leydig cell impairment emerges in men above the age of 70 years.

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Dietary patterns contribute to overall health and diseases of ageing but are understudied in older adults. As such, we first aimed to develop dietary indices to quantify Mediterranean Diet Score (MDS) utilisation and Ultra-processed Food (UPF) intake in a well-characterised cohort of relatively healthy community-dwelling older Australian adults. Second, we aimed to understand the relationship between these scores and the association of these scores with prevalent cardiometabolic disease and frailty.

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Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults are understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥70 years) and assess for associations with mortality.

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Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered.

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