Due to the high prevalence and incidence of depression among young adults, identifying potential prevention strategies during young adulthood is of great public health importance. Indeed, dietary intake is an important determinant of mental health during this stage of the lifespan. Dietary polyphenols, present in plant and plant-derived foods, have been inversely associated with depression in older cohorts (1) . However, the prospective association between polyphenol intake and depression remains unclear, particularly in young adults. As such, this study aimed to assess the prospective association between the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and depressive symptoms in young adults. Data from the Raine Study Generation 2 participants at 20-, 22-, and 27-year follow-ups (n = 1,484; 52.7% female; age range: 18 to 28 years) were used. The exposure variable, polyphenol intake, was estimated from self-reported dietary intakes using the Phenol-Explorer Database. We categorised energy-adjusted polyphenol intake into quartiles. The primary outcome was self-reported depressive symptoms assessed via the 21-item Depression, Anxiety, and Stress Scale (DASS) averaged across the three timepoints. Linear mixed-effects models were used to assess the association between the polyphenol intake exposures and depressive symptoms. Sociodemographic characteristics and lifestyle- and health-related behaviours were adjusted for in multivariable models. Participants in the highest quartiles for flavonol and hydroxybenzoic acid intake had lower depressive symptoms across time than participants in the lowest quartiles [flavonols (Q4 vs Q1 model-adjusted mean difference: −1.42, 95% CI: −2.52, −0.31); hydroxybenzoic acids (Q4 vs Q1: −1.37, CI: −2.48, −0.26)]. We found little to no evidence of a prospective association between depressive symptoms and quartiles of total polyphenols, polyphenol classes, and other polyphenol subclasses. The results from the current study in combination with previous studies in the field suggest that the intake of some, but not all, polyphenol subclasses may be useful targets for novel prevention strategies for depression. However, further mechanistic studies in human populations, and prospective studies in young adults and across the lifespan are required.

Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults. Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders. Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression. Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression. Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life.

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. Serum total testosterone concentrations were measured at baseline and year 3. Depressive symptoms were assessed annually using the CES-D-10 scale, with incident depression defined as a CES-D-10 score of ≥8. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) for incident depression, adjusted for potential confounders. RESULTS:During a median follow-up of 8.4 years, 1 449 participants experienced an episode of depression. Baseline total testosterone concentrations were not significantly associated with the risk of incident depression, whether treated as continuous variables (HR 1.00, 95% CI 0.99-1.01) or when categorized into quintiles. Similarly, changes in testosterone concentrations from baseline to year 3 did not predict incident depression (aHR 1.03, 95% CI 0.99-1.08). A subgroup analysis focusing on men with biochemical evidence of hypogonadism also found no association with incident depression. CONCLUSIONS:Our findings do not support an association between testosterone concentrations and the risk of developing depression in older men. These results suggest that testosterone is not an important factor in the pathogenesis of depression in this population. There may still be individual variability in response to testosterone changes and its potential impact on mood disorders.

BACKGROUND:With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions. METHODS:In this pooled analysis of individual-level data, we included original data from 19 prospective cohort studies conducted in Asia (Iran and Japan), Australia, Europe (Spain and Sweden), North America (USA and Mexico), and South America (Venezuela). We applied discrete-time hidden Markov models to estimate rates and ratios of prediabetes transitions to type 2 diabetes and normoglycaemia specific to age, sex, and race and ethnicity. We used Fine-Gray competing risk models to derive cohort-specific subhazard ratios (SHRs) for potential risk factors influencing these transitions. We subsequently pooled these SHRs using a random-effects meta-analysis. In subgroup analyses stratified by age, sex, race and ethnicity, and recruitment period, we used multivariate Cox models to investigate the degree of heterogeneity between studies. FINDINGS:76 092 participants (39 842 [52·3%] women and 36 250 [47·6%] men; mean age 51·1 years [SD 12·7]) with available data on glycaemic status from at least one follow-up visit were included in the analysis, of whom 56 837 (74·7%) had normoglycaemia and 19 255 (25·3%) had prediabetes. Median follow-up was 9·8 years (IQR 5·8-12·5). Within 10 years, individuals with prediabetes had a 12·5% probability of progressing to type 2 diabetes, whereas the probability of reverting to normoglycaemia was 36·1%. However, in the highest fasting plasma glucose quartile, the probability of progression increased to 16·1% and reversion decreased to 13·4%. Male sex, older age (≥55 years), and Latinx populations were associated with an increased risk of transitioning to type 2 diabetes. Risk factors that significantly reduced prediabetes reversion to normoglycaemia were overweight (SHR 0·88 [95% CI 0·76-0·99]), obesity (0·66 [0·52-0·81]), elevated waist-to-height ratio (0·82 [0·70-0·95]), elevated waist-to-hip ratio (0·79 [0·68-0·91]), and reduced HDL concentration (0·72 [0·59-0·84]). INTERPRETATION:Our findings highlight that reversion to normoglycaemia was more common than progression to type 2 diabetes among individuals with prediabetes, and that these transitions were strongly influenced by modifiable risk factors. The increased risk of progression with advancing age and among men underscores the importance of early identification and targeted interventions in population groups at high risk of type 2 diabetes. Furthermore, the elevated progression risk in individuals with higher fasting plasma glucose concentrations at baseline reinforces the need for timely detection and intervention during this crucial clinical window. FUNDING:Deakin University Postgraduate Research Scholarship.

BACKGROUND:The triglyceride-glucose index (TyG) has been proposed as a promising and clinically relevant biological marker of insulin resistance, which is thought to be prevalent among individuals at risk for depression. To date, there have been no longitudinal studies investigating the relationship between an elevated triglyceride-glucose index and subsequent depressive symptoms. METHODS:Health measures of 19,114 community-dwelling adults living in Australia and the United States of America, with a mean age of 75 years, were followed up for up to 11 years. Fasting triglyceride levels and fasting glucose levels were used to calculate the triglyceride-glucose index (TyG - the logarithmised product of fasting triglyceride level and fasting glucose divided by two), a marker of insulin resistance and risk for atherosclerotic cardiovascular disease. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression 10-item scale (CES-D-10), with a score ≥ 8 used to indicate a diagnosis of depression. The association between TyG and depression one year later was assessed using generalized estimating equations (GEE), with robust variance estimation to handle repeated measures clustered data. The main model was adjusted for age, gender, ethnicity, living arrangements, education, smoking status, alcohol consumption, body mass index, hypertension, type 2 diabetes, chronic kidney disease, a history of cancer, modified mini-mental state examination score, aspirin use, antidepressant use, diabetic medication use, and lipid-lowering medication use. In a secondary analysis, a Cox proportional hazards model was used to compare the incidence of depression up to 11 years between individuals with the highest baseline TyG group and the lowest baseline TyG. RESULTS:After adjustments for confounders, the GEE analysis showed no significant relationship between the highest quartile of TyG (compared to the lowest quartile of TyG) and depression one year later. The Cox proportional hazards model showed no significant difference between the highest and lowest TyG and depressive symptoms, when adjusted for the above covariates. CONCLUSIONS:An elevated triglyceride-glucose index was not associated with the later development of depression in fully adjusted models.

Background/Objectives: Evidence suggests a J-shaped association between alcohol consumption and depression, but it remains unclear whether this reflects a true causal effect, reverse causation, or methodological bias. This uncertainty is particularly relevant in older adults, who are at increased risk for both depression and alcohol-related harms. This study aimed to examine the association between varying levels of alcohol consumption and depression risk in community-dwelling older adults. Methods: We analyzed 16,563 community-dwelling older adults (mean age 75.1 ± 4.6 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Alcohol intake, reported at baseline and follow-up, was categorized as abstinent, occasional, moderate, or above-guideline. Both intention-to-treat (classified by baseline alcohol consumption, regardless of later changes) and per-protocol (using annual time-updated alcohol consumption ) analyses were performed. To address confounding, informative censoring, and selection bias, we applied marginal structural models with inverse probability weighting. Results: In per-protocol analyses, abstainers (OR 1.17), occasional drinkers (OR 1.11), and above-guideline drinkers (OR 1.15) were significantly associated with a higher risk of depression compared with moderate drinkers, consistent with a J-shaped association. Sensitivity analyses excluding former drinkers and those with baseline depressive symptoms showed similar results. The association remained robust after adjusting for social isolation, social support, social interactions, physical activity, pain, sleep duration, sleep difficulties, and sleep medication use (n = 14,892; Australian sub-sample), and did not differ by sex. Conclusions: Moderate alcohol consumption was associated with the lowest depression risk, confirming a J-shaped relationship after comprehensive confounder adjustment.

Excessive salt intake is a global health concern, particularly for individuals with hypertension (HTN). Limited research has examined the relationship between salt consumption and blood pressure control in Iranians. This study aimed to evaluate daily salt intake among hypertensive Iranians and its association with blood pressure management. Data were obtained from Iran’s 2021 STEPS survey. Sample hypertensive patients were defined by self-report, antihypertensive medication use, or blood pressure (BP) measurements (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). Daily salt intake was estimated using the Tanaka method based on spot urine sodium levels and categorized based on calculated quartiles. BP was analyzed in both continuous and binary forms (controlled/uncontrolled). Logistic regression was applied to assess relationship between daily salt intake and uncontrolled hypertension as outcome. The final analysis included 6,795 participants who were divided into four quartiles according to their daily salt intake. With a mean daily salt intake of 10.1 g [95

ABSTRACTIntroductionPost‐traumatic stress disorder (PTSD) is more prevalent in those with bipolar disorder (BD) than in the general population, with rates of PTSD as high as 55% in some BD cohorts. Despite this, little research explores the effects of pharmacotherapy treatments in those with comorbid BD and PTSD. This study aims to explore patterns of pharmacotherapy use at baseline and their impact on symptoms in individuals with BD alone and comorbid BD and PTSD.MethodsThe Systematic Treatment Enhancement Program for BD (STEP‐BD) cohort was utilised to examine and compare BD symptoms and pharmacotherapy treatments between those with BD alone (n = 3393) and those with comorbid BD and PTSD (n = 304). We conducted regression models to compare those with and without comorbid PTSD. Models included measures of depression, mania, functioning and quality of life over 24 months of the STEP‐BD study. We included baseline pharmacotherapies (lithium, valproate, antidepressants, antipsychotics and benzodiazepines) as predictor outcome variables in all models.ResultsAt baseline, reported use of lithium was lower in the comorbid BD and PTSD group, while the use of antidepressants, antipsychotics and benzodiazepines was significantly higher in the comorbid BD and PTSD than in the BD alone group. Benzodiazepine use was associated with a small improvement in depression symptom scores and poorer quality of life in those with comorbid BD and PTSD. Lastly, those with comorbid PTSD experienced higher levels of mania and depression symptoms and lower functioning and quality of life compared to BD alone, irrespective of pharmacotherapy treatment.ConclusionClinical trial participants with BD and PTSD reported worse symptoms and outcomes across 24 months of the STEP‐BD study compared to those without comorbid PTSD, regardless of baseline medication use. These results highlight the importance of considering comorbidity in the treatment of mental health conditions, specifically BD, and the need for further exploration of effective treatment options.

Longitudinal cohort studies across the lifespan suggest an association between ultra-processed food (UPF) and depression. However, the effect of UPF on depression and mental health in older adults has not been determined. Therefore, this study investigated the effect of UPF on depressive symptoms and mental health in community-dwelling older adults. A pragmatic target trial was designed and emulated using the ASPirin in Reducing Events in the Elderly longitudinal data. Participants were community-dwelling older adults (≥ 70 years) in Australia. We specified and emulated the protocol of a two-arm randomised pragmatic clinical trial using the level of UPF consumption as the intervention. Greater than or equal to 4 servings of UPF per day was considered the intervention, with less than 4 servings per day the control. Dietary consumption was assessed using a mail-based diet screening questionnaire, and the level of food processing was classified based on the NOVA classification. The study outcomes were depressive symptoms, defined as a score of ≥ 8 on the Center for Epidemiological Studies Depression 10-item scale, and general mental health, defined by the mental component summary score of the Short Form-12. We applied inverse probability treatment weighting to balance confounders. Marginal structural models were employed to estimate the population-level average effect of intervention using generalised estimated equations. A total of 11,192 participants (3415 intervention and 7777 control) were eligible for the emulation. High UPF consumption at time zero was associated with an increased risk of depressive symptoms at follow-ups (RR: 1.10; CI: 1.04–1.18). The finding was consistent with sensitivity analyses; after excluding participants on antidepressants at time zero, the risk of depressive symptoms in the intervention group was increased by 11

Objective: This study assessed the individual and combined associations of slow gait speed, weak grip strength, and depressive symptoms with the risk of serious falls in an aging population. Methods: This study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which collected adjudicated events on serious falls from Australian community-dwelling older adults (≥70 years). Cox proportional hazard models were employed to estimate adjusted hazard ratios (AHR). Results: Of 16,357 participants, 1505 (9.2 %) had serious falls over the median (IQR) follow-up of 4.4 (3.3–5.5) years. Slow gait, weak grip, and depressive symptoms at baseline were associated with serious falls (AHR = 1.38, 95 %CI: 1.22–1.56; AHR = 1.22, 95 %CI: 1.07–1.38, and AHR=1.28, 95 %CI:1.10–1.50, respectively). Combined slow gait, weak grip, and depressive symptoms were associated with a more than two-fold increase in the risk of serious falls (AHR=2.15, 95 %CI: 1.56–2.97). The presence of slow gait and weak grip were associated with a 66 % increase in the risk of serious falls (AHR=1.66, 95 %CI:1.40–1.97). Depressive symptoms worsened the risk of falls among individuals with chronic conditions such as diabetes. Conclusion: Combined gait speed, grip strength, and depressive symptoms have a strong association with serious falls in an aging population. Therefore, incorporating strength and mobility training interventions to improve physical functions and addressing depression through timely diagnosis and effective treatment may help to prevent the risk of falls among older adults.

ABSTRACT Introduction While type 2 diabetes (T2DM) has become a major health issue in the North American and Caribbean region, the effects of weight change on incident T2DM, conditional on either initial or attained weight, are poorly addressed. Therefore, we aimed to assess the impact of 3‐year weight change on incident T2DM over 6 years among US individuals. Methods A total of 8377 participants aged 45–64 years (4601 women), free of T2DM or cancer at baseline from the Atherosclerosis Risk in Communities (ARIC) study were included. Weight measurements were taken at baseline (visit 1, 1987–89) and approximately 3 years later (visit 2, 1990–92). Participants were categorised based on their weight change ratio into ≥ 5% weight loss, stable (±5%), and ≥ 5% weight gain. Cox proportional hazards models, adjusting for known diabetes risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident T2DM, with stable weight (±5%) as the reference category. Results During a median follow‐up period of 6 years, participants were classified into three categories: 361 persons remained stable (±5%), 47 with ≥ 5% loss, and 135 with ≥ 5% gain. In multivariable analysis, after adjustment with initial weight, ≥ 5% weight gain and loss were significantly associated with higher [HR (95% CI): 1.68 (1.36–2.06), p‐value < 0.0001] and lower [0.73 (0.53–1.00), p‐value = 0.05] risks of incident T2DM, respectively. When adjusted for attained weight, weight gain ≥ 5% remained a significant risk factor for T2DM [1.51 (1.21–1.88)]; however, weight loss ≥ 5% lost statistical significance [0.84 (0.60–1.17), p‐value = 0.31]. Conclusions We found a robust association between weight gain and incident T2DM; however, the beneficial impact of weight loss was significantly attenuated after considering the attained weight.

The extent to which genetic predisposition contributes to late-life depression risk, particularly after age 70, remains unclear, despite the high prevalence of depression in this age group and the variability in risk factors by age. This study investigated the association between a polygenic score (PGS) and depression outcomes, including severity, trajectories of depression, and antidepressant medication use, in a longitudinal cohort of 12,029 genotyped older adults of European descent aged ≥70 years, with no history of diagnosed cardiovascular disease events, dementia, or permanent physical disability at baseline. Participants were followed for a median of 4.7 years. The PGS was derived using the latest Psychiatric Genomics Consortium data for major depression. Depression was defined by the CES-D-10 score thresholds of ≥8 (primary outcome), ≥10, and ≥12 (secondary outcomes), alongside antidepressant medication use and four previously established longitudinal trajectories of depressive symptoms: low (non-depressed), moderate (subthreshold), high (persistent), and initially low but increasing (emerging). Multivariable models were used to examine associations between the PGS (per standard deviation, SD) and outcomes, adjusting for covariates. At baseline, mean participant age was 75.1 years, 54.9% were female, and 9.1% had depression (CES-D-10 ≥ 8). The PGS was significantly associated with baseline depression (OR = 1.23 [1.15–1.31]), incident depression (HR = 1.18 [1.14–1.23]) and antidepressant medication use (OR = 1.39 [1.31–1.47]). Compared with non-depressed participants, the PGS was associated with increasing severity of depression trajectory classes (subthreshold depression OR = 1.15 [1.11–1.20], emerging depression OR = 1.22 [1.13–1.31], persistent depression OR = 1.40 [1.31–1.49]). These findings suggest that the PGS may play an important role in risk stratification for late-life depression.

BackgroundTelehealth-facilitated models of palliative care are a patient-focused way to deliver specialist care in or closer to home for people with a life-limiting illness. Telehealth can increase access to palliative care and support people experiencing symptoms of advanced disease in their own home, reducing the discomfort of travel. This retrospective cohort study examines the activity and outcomes of a regional telehealth-facilitated palliative care service to (i) describe which patients are most likely to use telehealth; and (ii) explore possible impacts of telehealth on patient outcomes including place of death, timely access to care, responsiveness to urgent needs and pain management.MethodsAnalysis of service activity data (patient demographics, care modality, consultation frequency) and Palliative Care Outcomes Collaborative data registry (place of death, timely access to palliative care, responsiveness to urgent needs as measured by time in unstable phase, pain management) were undertaken. Outcomes were compared between patients who had no videoconsultations (n = 683) and those who had one or more videoconsultations (n = 524).ResultsCompared to people who had no videoconsultations, those who had at least one appointment via video were: more than twice as likely to die at home and spent a shorter amount of time in the unstable phase of palliation. Mixed results were found regarding timely access to palliative care. There was no significant difference in pain management between consultation modes.ConclusionTelehealth-facilitated palliative care has multiple benefits, including the increased likelihood of fulfilling someone's wish to die at home, often their preferred place of death.

Background:Achieving survival free from physical disability or neurocognitive impairment, known as disability-free survival (DFS), is a key public health goal. This study aimed to (1) determine the long-term interactive effects of depression and cardiometabolic diseases (CMDs) on DFS, and (2) explore any associated antidepressant treatment effect on improvements in DFS among older adults. Methods:We used data from the ASPREE trial and its observational follow-ups (2010-2019), involving community-dwelling adults aged ≥ 70 years (≥65 for U.S. minorities). Time-updated Cox models were used to estimate the combined effect of depression and CMDs (type 2 diabetes, dyslipidemia, hypertension, chronic kidney disease, metabolic-associated steatotic liver disease, and major adverse cardiovascular events) as well as cardiometabolic multimorbidity (≥2 CMDs) on DFS. To evaluate the improvement in DFS associated with antidepressant treatment in individuals with depression, we estimated the number needed to treat (NNT) to achieve a one-year increase in DFS through antidepressant therapy. Findings:18,739 participants (mean [SD] age, 75.1 [4.6] years; 56.0% female) were included, with a median follow-up of seven years; individuals with both depression and CMDs demonstrated a significantly lower DFS compared to those without either condition. In individuals with depressive symptoms, antidepressant use was associated with a median increase in DFS of 2.95 years (95% CI, 2.12-3.04), with an estimated NNT of 8.05 (95% CI, 5.63-14.86) associated with a one-year increase in DFS. Interpretation:Integrating depression treatment into chronic disease management, when appropriate, is associated with an improvement in DFS among older adults. Funding:Deakin University Postgraduate Research Scholarship.

In a single-blind, two-arm, randomized controlled-feeding trial (May 2021-February 2022), 47 women (30-65 years, BMI 30-45 kg/m2) are randomized to either a food-based or a supplement-based very-low-energy diet (VLED: 800-900 kcal/d) for 3 weeks. The food-based VLED comprises pre-packaged meals (∼93% whole-food ingredients), while the supplement-based VLED comprises shakes, soups, bars, and desserts (∼70% industrial ingredients). The primary outcome is species-level alpha diversity (Shannon index). Secondary outcomes include species richness, beta diversity, taxonomic composition, functional potential, anthropometrics, serum biomarkers, mental health, sleep, and gastrointestinal symptoms. Modified intention-to-treat (mITT) analyses (n = 45) assess diet group × time interactions as beta coefficients (β) with 95% confidence intervals (CIs). A between-group differential change is observed for the Shannon index, with a greater increase in the food-based group (mITT β: 0.37, 95% CI: 0.15-0.60). The food-based group also shows greater species richness, smaller beta diversity shifts, and compositional changes preserving fiber-degrading, health-associated taxa.

OBJECTIVES:Although cardiovascular disease (CVD) is responsible for a large global burden of disease, a large proportion of CVD incidence can be prevented through health literacy (ie, the skills and resources of an individual to access, understand, and use information to make decisions and act on one's own health and health care). We reviewed and synthesized peer-reviewed literature on health literacy and primary prevention of CVD. METHODS:We followed methods from the review's previously published protocol, which outlined a search strategy conducted on August 16, 2024, for 6 databases, linking concepts of health literacy and CVD risk and its associated knowledge, attitudes, or practices. One reviewer screened and extracted all articles, and a second reviewer screened a randomly selected 10% of articles at each stage to examine interrater agreement. We used the Office of Health Assessment and Translation Risk of Bias Tool to assess the potential risk of bias. RESULTS:Of 35 studies in the synthesis, 26 (74%) were cross-sectional and 21 (60%) measured functional health literacy only. Twenty-three articles investigated health literacy as an exposure variable, 20 of which reported significant results. Eight articles examined the administration of health literacy interventions to populations at risk of CVD, and 4 presented health literacy profiles of populations at risk of CVD. Each study demonstrated at least 1 area of potential risk of bias but was deemed low risk of bias overall. CONCLUSIONS:Several studies in this review found an association between health literacy and CVD risk. More longitudinal studies, as well as studies that measure health literacy more deeply than simply reading and comprehending health texts, are needed to better understand the extent of this relationship.

Aims/hypothesisWe aimed to investigate the association between reversion to normoglycaemia among individuals with prediabetes (fasting plasma glucose 5.6-6.9 mmol/l in the absence of other criteria for type 2 diabetes) and the subsequent risk of type 2 diabetes, and to examine whether concurrent favourable cardiometabolic risk factor profiles modify this association.MethodsWe used individual-level data from prospective cohorts in the USA, Australia and Asia. Participants with prediabetes at baseline, with at least two follow-ups (n=8191) at median intervals of 2.9 years (IQR 2.3-9.0) and 3.1 years (IQR 2.6-3.6), were classified into restoration of normoglycaemia and persistent prediabetes groups based on the glucose status at the first follow-up (normoglycaemia or prediabetes). Type 2 diabetes occurrence was assessed at subsequent follow-ups. Hierarchical mixed-effects proportional hazards Weibull models estimated type 2 diabetes risk, adjusting for age, sex and cardiometabolic risk factors. A subgroup analysis evaluated the combined association of normoglycaemia restoration and normal cardiometabolic risk factor levels on subsequent type 2 diabetes risk.ResultsIn individuals with prediabetes, normoglycaemia restoration compared with persistent prediabetes was associated with a 51% lower risk of developing type 2 diabetes. Even lower risks were observed among individuals with concurrent favourable cardiometabolic profiles, including non-smokers (HR 0.20, 95% CI 0.10, 0.31), and those with normal BMI (0.16, 95% CI 0.06, 0.27), waist circumference (0.22, 95% CI 0.12, 0.33), waist-to-height ratio (0.15, 95% CI 0.03, 0.26), WHR (0.17, 95% CI 0.05, 0.28), and systolic (0.20, 95% CI 0.11, 0.30) and diastolic (0.25, 95% CI 0.12, 0.38) blood pressure, triacylglycerol (0.24, 95% CI 0.13, 0.35) and HDL-cholesterol levels (0.21, 95% CI 0.13, 0.29). Weight loss combined with normoglycaemia restoration was also associated with lower type 2 diabetes risk (0.18, 95% CI 0.07, 0.30) compared with weight gain and persistent prediabetes.Conclusions/interpretationOur results suggest that prioritising normoglycaemia restoration during the prediabetes stage in clinical guidelines may contribute to reducing the risk of type 2 diabetes, particularly when accompanied by favourable cardiometabolic health profiles.

AIMS:There has been a global shift from nutrient-dense diets to an ultra-processed food pattern, which is linked to adverse health outcomes, including cardiovascular mortality. However, there is limited evidence in an Australian setting. Furthermore, many people in Australia have emigrated from countries with heart-healthy diets. This study explored the association between ultra-processed food exposure and cardiovascular mortality in an Australian cohort. METHODS AND RESULTS:Data were derived from the Melbourne Collaborative Cohort Study. Food frequency questionnaire data collected at baseline were used to estimate ultra-processed food exposure according to the Nova classification system. Cardiovascular deaths were identified using data linkage between baseline (1990-94) and 31 March 2019. Fine and Gray competing risk models were fitted to assess the association between energy-adjusted ultra-processed food exposure and cardiovascular mortality, accounting for other types of mortality as competing risks. We included 39 544 participants (mean age 55.1 years at baseline, 60% female). During the follow-up period, which spanned 919 379 person-years and a median follow-up of 25.1 years, 4229 cardiovascular deaths occurred. After adjusting for sociodemographic, lifestyle, and health-related factors, participants with the highest relative intake of ultra-processed food had 19% higher risk of cardiovascular mortality (hazard ratiohigh (quartile 4) vs. low (quartile 1) category = 1.19, 95% confidence intervals: 1.09-1.29, P-value for trend < 0.001). CONCLUSION:Aligning with findings from the USA and Europe, higher exposure to the ultra-processed food pattern was prospectively associated with a higher risk of cardiovascular mortality.

OBJECTIVE:To investigate the association between thyroid-stimulating hormone (TSH) levels and depression in older adults. DESIGN:Prospective cohort study with an 11-year follow-up period. SETTING:Community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial and its follow-up observational study in Australia. PARTICIPANTS:About 9,050 adults aged ≥70 years with baseline TSH measurements and depression assessments. Participants with thyroid cancer, baseline depression, or thyroid-altering medications were excluded. MEASUREMENTS:Depression was assessed annually using the Center for Epidemiological Studies Depression Scale (CES-D-10) using a cut score of 12, and hospital admission records. TSH was measured at baseline and year 3, categorized as low (<0.34 mU/L), normal (0.34-3.75 mU/L), or high (>3.75 mU/L). RESULTS:Cross-sectional analyses found no significant association between TSH levels and depression at baseline (p = 0.79) or year 3 (p = 0.054). Longitudinal analyses revealed no relationship between baseline or time-varying TSH levels and incident depression over the follow-up period (HR = 1.0, 95% CI: 0.96-1.05). CONCLUSIONS:TSH levels are not associated with prevalent or incident depression in older community-dwelling adults. These findings should guide screening approaches for depression in older adults.

BACKGROUND:Current cardiovascular disease (CVD) risk prediction models tailored for older adults are inadequate. This study aimed to validate, update and assess the utility of widely used CVD risk prediction models including American College of Cardiology/American Heart Association, 2008 Framingham, GloboRisk, National Vascular Disease Prevention Alliance and Predict1 originally developed for middle-aged population, as well as an age-specific Systematic COronary Risk Evaluation 2-Older Person model, in Australian and the US community-dwelling older adults. METHODS:Participants, without history of CVD events, dementia or physical disability, enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) clinical trial and ASPREE-eXTention observational post-trial follow-up, were considered for CVD risk prediction. The main outcome was predicted CVD risk from adjudicated CVD events. The performance of the original, recalibrated (adjusting models' intercept and slope) and updated (adjusting models' coefficients) models was evaluated by discrimination (C statistic), calibration (calibration plots) and clinical utility (decision curves). Models were extended by incorporating predictors including serum creatinine, depression and socioeconomic status index (Index of Relative Socio-economic Advantage and Disadvantage, IRSAD) into models' equation, and the changes in discrimination were evaluated. RESULTS:Among 15 618 adults (mean age 75 (4.4) years), 520 men and 498 women experienced CVD events over a median follow-up of 6.3 (IQR: 5.2-7.7) years. Following updating, the discrimination power of models increased for both sexes (C statistics ranged 0.62-0.64 for men and 0.68-0.69 for women). Updated models indicated good calibration, with an added net benefit at the risk thresholds ranging from 4%-10% for women to 5%-12% for men. Incorporating IRSAD, depression and serum creatinine did not improve CVD risk discrimination of updated models. CONCLUSIONS:Updating models, by adjusting model coefficients to better reflect the characteristics and risk factors of older adults, improves CVD risk prediction in a large cohort of relatively healthy Caucasian population aged 70+. Further external validation in diverse older populations including those with frailty and multimorbidity is recommended before clinical implementation.