Importance: Although diabetes is a risk factor for dementia, the effect of glucose-lowering therapy for prevention of incident dementia is uncertain.Objective: To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes.Data Sources: The PubMed and Embase databases were searched for studies published from inception of the database to July 11, 2024.Study Selection: Randomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores. Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials. Inclusion criteria were assessed independently and inconsistencies were resolved by consensus.Data Extraction and Synthesis: Data were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models were used to estimate a pooled treatment effect.Main Outcomes and Measures: The primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia, and change in cognitive scores.Results: Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04).Conclusions and Relevance: While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.

Purpose: Increasing potassium intake, especially in populations with low potassium intake and high sodium intake, has emerged as an important population-level intervention to reduce cardiovascular events. Current guideline recommendations, such as those made by the World Health Organisation, recommend a potassium intake of > 3.5 g/day. We sought to determine summary estimates for mean potassium intake and sodium/potassium (Na/K) ratio in different regions of the world. Methods: We performed a systematic review and meta-analysis. We identified 104 studies, that included 98 nationally representative surveys and 6 multi-national studies. To account for missingness and incomparability of data, a Bayesian hierarchical imputation model was applied to estimating summary estimates of mean dietary potassium intake (primary outcome) and sodium/potassium ratio. Results: Overall, 104 studies from 52 countries were included (n = 1,640,664). Mean global potassium intake was 2.25 g/day (57 mmol/day) (95% credible interval (CI) 2.05–2.44 g/day), with highest intakes in Eastern and Western Europe (mean intake 3.53g/day, 95% CI 3.05–4.01 g/day and 3.29 g/day, 95% CI 3.13–3.47 g/day, respectively) and lowest intakes in East Asia (mean intake 1.89 g/day; 95% CI 1.55–2.25 g/day). Approximately 31% (95% CI, 30–41%) of global population included have an estimated potassium intake > 2.5 g/day, with 14% (95% CI 11–17%) above 3.5 g/day. Conclusion: Global mean potassium intake (2.25 g/day) falls below current guideline recommended intake level of > 3.5 g/day, with only 14% (95% CI 11–17%) of the global population achieving guideline-target mean intake. There was considerable regional variation, with lowest mean potassium intake reported in Asia, and highest intake in Eastern and Western Europe.

Importance: Psychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions.Objectives: To determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population.Design, Setting, and Participants: INTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress.Exposures: Psychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work.Main Outcomes and Measures: The association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control.Results: Among 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years; that of controls, 61.3 (13.3) years; 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58]; P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98]; P < .001 for interaction) for acute stroke.Conclusions and Relevance: Psychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.

Quantifying the proportion of dementia attributable to highly prevalent modifiable risk factors, such as hypertension, is important in informing effective dementia prevention strategies. We aim to quantify the population attributable fraction (PAF) of hypertension for dementia (the proportion of dementia cases that would not occur if hypertension was eliminated) at global, regional, and national levels. In this study, we searched international and governmental websites for global, regional, and national data reporting population hypertension (according to 10-year age categories) and dementia prevalence. MEDLINE was searched for studies reporting the risk of dementia from age at hypertension diagnosis from database inception to December 31, 2022. Longitudinal observational studies with >500 participants reporting hazard ratios by age at hypertension diagnosis for risk of future all-cause dementia were eligible for inclusion. Studies excluded had cross-sectional methodology, specific vascular dementia or ‘cognitive impairment’ outcomes, and no age-specific metrics of association reported. The PAF of hypertension for dementia was calculated globally and for each country and region worldwide. Data from the Global Burden of Disease, United Nations Population Prospectus, NCD Risk Factor Collaboration, UK Biobank, and Atherosclerosis Risk in Communities Study were obtained. 186 countries reported dementia and hypertension prevalence data. The global PAF of hypertension for dementia was 15.8% [95% Credible Interval (CI), 8.8%–22.7%]. Latin America and the Caribbean (18.0% [95% CI, 9.4%–26.6%]), and Europe (17.2% [95% CI, 9.6%–24.7%]) had the highest PAF of hypertension for dementia. Hypertension diagnosed between the ages of 30–44 had the highest age-specific global attributable fraction for dementia (8.4% [95% CI, 3.4%–13.5%]), followed by ages 45–54 (2.92% [ 95% CI, 0.96%–4.88%]), 55–64 (2.59% [95% CI, 1.15%–4.03%]) and 65–74 (1.82% [95% CI, −2.31%–5.96%]). The population attributable risk of hypertension for dementia is 15.8%, suggesting that optimal detection and treatment, particularly at midlife, has the potential to markedly reduce the global burden of dementia. 10.13039/100010269 Wellcome Trust ; Health Research Board of Ireland; 10.13039/100000957 Alzheimer's Association .

Introduction: Gestational diabetes (GDM), defined as hyperglycemia with onset or initial recognition during pregnancy, has a rising prevalence paralleling the rise in type 2 diabetes (T2DM) and obesity. GDM is associated with short-term and long-term consequences for both mother and child. Therefore, it is crucial we efficiently identify all cases and initiate early treatment, reducing fetal exposure to hyperglycemia and reducing GDM-related adverse pregnancy outcomes. For this reason, GDM screening is recommended as part of routine pregnancy care. The current screening method, the oral glucose tolerance test (OGTT), is a lengthy, cumbersome and inconvenient test with poor reproducibility. Newer biomarkers that do not necessitate a fasting sample are needed for the prompt diagnosis of GDM. The aim of this scoping review is to highlight and describe emerging protein biomarkers that fulfill these requirements for the diagnosis of GDM. Materials and Methods: This scoping review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for scoping reviews using Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing & Allied Health Literature (CINAHL), PubMed, Embase and Web of Science with a double screening and extraction process. The search included all articles published in the literature to July 2020. Results: Of the 3519 original database citations identified, 385 were eligible for full-text review. Of these, 332 (86.2%) were included in the scoping review providing a total of 589 biomarkers studied in relation to GDM diagnosis. Given the high number of biomarkers identified, three post hoc criteria were introduced to reduce the items set for discussion: we chose only protein biomarkers with at least five citations in the articles identified by our search and published in the years 2017–2020. When applied, these criteria identified a total of 15 biomarkers, which went forward for review and discussion. Conclusions: This review details protein biomarkers that have been studied to find a suitable test for GDM diagnosis with the potential to replace the OGTT used in current GDM screening protocols. Ongoing research efforts will continue to identify more accurate and practical biomarkers to take GDM screening and diagnosis into the 21st century.

Background and Objectives Depression has been reported to be a risk factor for acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type Methods INTERSTROKE is an international case-control study of risk factors for first acute stroke, conducted in 32 countries. Cases were patients with CT or MRI confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of pre-stroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of pre-stroke depressive symptoms with post-stroke functional outcome, measured with the modified-Rankin scale at 1-month after stroke. Results Of 26,877 participants, 40.4% were women, the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared to controls (18.3%vs.14.1%,p < 0.001) and differed by region (p_interaction < 0.001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses pre-stroke depressive symptoms were associated with greater odds of acute stroke (OR 1.46, 95%CI 1.34–1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95%CI 1.28–1.91) and ischemic stroke (OR 1.44, 95%CI 1.31–1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While pre-admission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95%CI 0.94–1.10), they were associated with a greater odds of poor functional outcome at 1-month after acute stroke (OR 1.09, 95%CI 1.01–1.19). Discussion In this global study we recorded that depressive symptoms are an important risk factor for acute stroke, including both ischemic and hemorrhagic stroke. Pre-admission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in post-stroke recovery.