Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

AIMS: Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia. METHODS AND RESULTS: Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. CONCLUSION: The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia. CLASSIFICATION OF EVIDENCE: Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Reproductive factors and the risk of incident dementia: A cohort study of UK Biobank participants.

BACKGROUND: Women's reproductive factors have been associated with the risk of dementia; however, these findings remain uncertain. This study aimed to examine the risk of incident all-cause dementia associated with reproductive factors in women and the number of children in both sexes and whether the associations vary by age, socioeconomic status (SES), smoking status, and body mass index (BMI) in the UK Biobank. METHODS AND FINDINGS: A total of 273,240 women and 228,957 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia. Multiple adjusted models included age at study entry, SES, ethnicity, smoking status, systolic blood pressure, BMI, history of diabetes mellitus, total cholesterol, antihypertensive drugs, and lipid-lowering drugs. Over a median of 11.8 years follow-up, 1,866 dementia cases were recorded in women and 2,202 in men. Multiple adjusted HRs ((95% confidence intervals (CIs)), p-value) for dementia were 1.20 (1.08, 1.34) (p = 0.016) for menarche <12 years and 1.19 (1.07, 1.34) (p = 0.024) for menarche >14 years compared to 13 years; 0.85 (0.74, 0.98) (p = 0.026) for ever been pregnant; 1.43 (1.26, 1.62) (p < 0.001) for age at first live birth <21 compared to 25 to 26 years; 0.82 (0.71, 0.94) (p = 0.006) for each abortion; 1.32 (1.15, 1.51) (p = 0.008) for natural menopause at <47 compared to 50 years; 1.12 (1.01, 1.25) (p = 0.039) for hysterectomy; 2.35 (1.06, 5.23) (p = 0.037) for hysterectomy with previous oophorectomy; and 0.80 (0.72, 0.88) (p < 0.001) for oral contraceptive pills use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes: Compared with those with 2 children, for those without children, the multiple adjusted HR ((95% CIs), p-value) was 1.18 (1.04, 1.33) (p = 0.027) for women and 1.10 (0.98, 1.23) (p = 0.164) for men, and the women-to-men ratio of HRs was 1.09 (0.92, 1.28) (p = 0.403); for those with 4 or more children, the HR was 1.14 (0.98, 1.33) (p = 0.132) for women and 1.26 (1.10, 1.45) (p = 0.003) for men, and the women-to-men ratio of HRs was 0.93 (0.76, 1.14) (p = 0.530). There was evidence that hysterectomy (HR, 1.31 (1.09, 1.59), p = 0.013) and oophorectomy (HR, 1.39 (1.08, 1.78), p = 0.002) were associated with a higher risk of dementia among women of relatively lower SES only. Limitations of the study include potential residual confounding and self-reported measures of reproductive factors, as well as the limited representativeness of the UK Biobank population. CONCLUSIONS: In this study, we observed that some reproductive events related to shorter cumulative endogenous estrogen exposure in women were associated with higher dementia risk, and there was a similar association between the number of children and dementia risk between women and men.

Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank.

BACKGROUND: Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). METHODS: Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. RESULTS: 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62-6.16] for women and 8.42 [8.07-8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77-0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02-1.13] in women and 0.98 [0.93-1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer's disease). CONCLUSIONS: Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial.

AIM: To estimate the associations between risk factors and cognitive decline (CD)/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death. MATERIALS AND METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression. RESULTS: During a median 5-year follow-up, 1827 participants (43.2% women) had CD/dementia (1718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had lower odds of CD/dementia than men (odds ratio [OR] [95% confidence interval], 0.88 [0.77, 1.00]); older age, higher total cholesterol, HbA1c, waist circumference, waist-to-height ratio, moderately increased albumin-creatinine ratio, stroke/transient ischaemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women-to-men ratio of ORs [ROR], 1.05 [1.00, 1.10] per 5 cm) and presence of anxiety/depression (ROR, 1.28 [1.01, 1.63]) were associated with greater ORs for CD/dementia in women than men. CONCLUSIONS: Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms that underlie these sex differences.

Who is the main caregiver of the mother during the doing-the-month: is there an association with postpartum depression?

BACKGROUND: To examine the relationship between the main caregiver during the "doing-the-month" (a traditional Chinese practice which a mother is confined at home for 1 month after giving birth) and the risk of postpartum depression (PPD) in postnatal women. METHODS: Participants were postnatal women stayed in hospital and women who attended the hospital for postpartum examination, at 14-60 days after delivery from November 1, 2013 to December 30, 2013. Postpartum depression status was assessed using the Edinburgh Postnatal Depression Scale. Univariate and multivariable logistic regressions were used to identify the associations between the main caregiver during "doing-the-month" and the risk of PPD in postnatal women. RESULTS: One thousand three hundred twenty-five postnatal women with a mean (SD) age of 28 (4.58) years were included in the analyses. The median score (IQR) of PPD was 6.0 (2, 10) and the prevalence of PPD was 27%. Of these postnatal women, 44.5% were cared by their mother-in-law in the first month after delivery, 36.3% cared by own mother, 11.1% by "yuesao" or "maternity matron" and 8.1% by other relatives. No association was found between the main caregivers and the risk of PPD after multiple adjustments. CONCLUSIONS: Although no association between the main caregivers and the risk of PPD during doing-the-month was identified, considering the increasing prevalence of PPD in Chinese women, and the contradictions between traditional culture and latest scientific evidence for some of the doing-the-month practices, public health interventions aim to increase the awareness of PPD among caregivers and family members are warranted.

Protein signatures associated with loneliness and social isolation: plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization.

The understanding of biological pathways related to loneliness and social isolation remains incomplete. Cutting-edge population-based proteomics offers opportunities to uncover novel biological pathways linked to social deficits. This study employed a proteome-wide and data-driven approach to estimate the cross-sectional associations between objective measures of social connections (i.e., social isolation) and subjective measures (i.e., loneliness) with protein abundance, using the English Longitudinal Study of Ageing. Greater social isolation was associated with higher levels of 11 proteins (TNFRSF10A, MMP12, TRAIL-R2, SKR3, TNFRSF11A, VSIG2, PRSS8, FGFR2, KIM1, REN, and NEFL) after minimal adjustments; and three proteins were significantly associated after full adjustments (TNFRSF10A, TNFRSF11A, and HAOX1). Findings from two-sample Mendelian randomization indicated that a lower frequency of in-person social contact with friends or family causally increased levels of TNFRSF10A, TRAIL-R2, TNFRSF11A, and KIM1, and decreased the level of NEFL. The study also highlighted several enriched biological pathways, including necrosis and cell death regulation, dimerization of procaspase-8, and inhibition of caspase-8 pathways, which have previously not been linked to social deficits. These findings could help explain the relationship between social deficits and disease, confirming the importance of continuing to explore novel biological pathways associated with social deficits.

Unraveling the role of plasma proteins in dementia: insights from two cohort studies in the UK, with causal evidence from Mendelian randomization.

Population-based proteomics offer a groundbreaking avenue to predict dementia onset. This study employed a proteome-wide, data-driven approach to investigate protein-dementia associations in 229 incident all-cause dementia (ACD) among 3,249 participants from the English Longitudinal Study of Ageing (ELSA) over a median 9.8-year follow-up, then validated in 1,506 incident ACD among 52,745 individuals from the UK Biobank (UKB) over median 13.7 years. NEFL and RPS6KB1 were robustly associated with incident ACD; MMP12 was associated with vascular dementia in ELSA. Additional markers EDA2R and KIM1 (HAVCR1) were identified from sensitivity analyses. Combining NEFL and RPS6KB1 with other factors yielded high predictive accuracy (area under the curve (AUC)=0.871) for incident ACD. Replication in the UKB confirmed associations between identified proteins with various dementia subtypes. Results from reverse Mendelian Randomization also supported the role of several proteins as early dementia biomarkers. These findings underscore proteomics' potential in identifying novel risk screening targets for dementia.

Trends of mean systolic and diastolic blood pressure among adults in Shenzhen, China, 1997-2018: findings from three rounds of the population-based survey.

OBJECTIVE: To quantify the trends in systolic and diastolic blood pressure (BP) among adults in Shenzhen from 1997 to 2018. DESIGN: Cross-sectional study. SETTINGS: The data were collected from all districts in Shenzhen, China in the years of 1997, 2009 and 2018 by multistage cluster sampling procedure. PARTICIPANTS: Participants were residents aged 18-69 years in Shenzhen, China. A total of 26 621 people were included: 8266 people in 1997, 8599 people in 2009 and 9756 people in 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: All participants were surveyed about their sociodemographic and lifestyle information. BP was measured by trained physicians using a mercury sphygmomanometer. Hypertension was defined as systolic BP of at least 140 mm Hg and diastolic BP of at least 90 mm Hg, self-reported use of antihypertensive medications or both. Hypertension control was defined as systolic BP values of less than 140 mm Hg and diastolic BP values of less than 90 mm Hg. RESULT: Age-adjusted mean systolic BP increased from 117±16 mm Hg to 123±15 mm Hg (p<0.001) in males, and from 113±18 mm Hg to 115±16 mm Hg (p<0.001) in females from 1997 to 2018. Diastolic BP among males increased from 75 mm Hg (SD=11) to 79 mm Hg (SD=11) and increased from 71 mm Hg (SD=10) to 73 mm Hg (SD=10) among females between 1997 and 2018 (p<0.001). Rate of hypertension rose rapidly from 17.71% (95% CI: 16.60% to 18.90%) in 2009 to 24.01% (95% CI: 22.84% to 25.22%) in 2018 among males (p<0.001), whereas the prevalence among females remained stable at around 13.5% (p=0.98). Both awareness and treatment rates of hypertension among males and females showed a decreased trend between 2009 and 2018, while no significant changes were observed for control rates. CONCLUSIONS: The mean systolic BP and diastolic BP among adults in Shenzhen increased from 1997 to 2018, and no improvements in hypertension awareness, treatment and control rates were found.

Clinical outcomes by atherosclerotic cardiovascular disease risk score and blood pressure level in high risk individuals with type 2 diabetes.

Clinical practice guidelines for patients with diabetes recommend using blood pressure (BP) and atherosclerotic cardiovascular disease (ASCVD) risk to guide antihypertensive treatment. While this approach directs treatment to patients who should receive a large ASCVD risk reduction, its effect on other outcomes is uncertain. The aim of this study was to assess the contributions of systolic blood pressure level (SBP) and predicted 10-year ASCVD risk using Pooled Cohort risk equations to the prediction of major macrovascular disease, death and major microvascular disease in patients with diabetes. Data came from 7426 individuals with type 2 diabetes (T2D) without macrovascular disease at baseline in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The risk for major macrovascular events and death increased progressively across ASCVD risk categories. Compared to participants with 10-year predicted ASCVD risk <20% and SBP <130 mmHg, the hazard ratios (HRs) (95% confidence intervals (CIs)) associated with SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20-34% and ≥35% were 1.01 (0.58, 1.77), 1.90 (1.28, 2.84) and 2.82 (1.98, 4.01) for major macrovascular disease, respectively, and 0.83 (0.42, 1.62), 1.79 (1.13, 2.82) and 3.29 (2.22, 4.88) for death, respectively. The risk for major microvascular disease increased with BP regardless of ASCVD risk; HRs for SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20-34% and ≥35% vs. ASCVD risk <20% and SBP <130 mmHg were 1.52 (1.08,2.13), 1.47 (1.10, 1.96) and 1.23 (0.94, 1.60), respectively. ASCVD risk in addition to SBP improved the estimation of major macrovascular events and death but not major microvascular events among individuals with T2D.

Current and future burdens of heat-related dementia hospital admissions in England.

INTRODUCTION: The impacts of a changing climate on current and future dementia burdens have not been widely explored. METHODS: Time-series negative binomial regression analysis was used to assess acute associations between daily ambient temperature and counts of emergency admissions for dementia in each Government region of England, adjusting for season and day-of-week. Using the latest climate and dementia projections data, we then estimate future heat-related dementia burdens under a high emission scenario (Representative Concentration Pathway (RCP8.5), where global greenhouse gas (GHG) emissions continue to rise, and a low emissions scenario (RCP2.6), where GHG emissions are sizeably reduced under a strong global mitigation policy. RESULTS: A raised risk associated with high temperatures was observed in all regions. Nationally, a 4.5% (95% Confidence interval (CI) 2.9%-6.1%) increase in risk of dementia admission was observed for every 1 °C increase in temperature above 17 °C associated with current climate. Under a high emissions scenario, heat-related admissions are projected to increase by almost 300% by 2040 compared to baseline levels. CONCLUSIONS: People living with dementia should be considered a high-risk group during hot weather. Our results support arguments for more stringent climate change mitigation policies.

Contextualising sex and gender research to improve women's health: An early- and mid-career researcher perspective.

The field of sex and gender research in health and medicine is growing, and many early- and mid-career researchers (EMCRs) are developing skills in this area. As EMCRs specialising in sex and gender research, we aim to better understand sex- and gender-based determinants of human health, challenge long-standing and pervasive gender biases, and contribute to improving the evidence base upon which clinical guidelines and policy interventions are developed. To effectively achieve these goals, we believe that EMCRs would benefit from understanding the challenges of working in this space and participate in driving change in three key areas. First, in creating greater links between the goals of sex and gender research and addressing systemic bias against women and gender minorities, to effectively translate knowledge about sex and gender differences into improved health outcomes. Second, in expanding the reach of sex and gender research to address women's health in an intersectional way and ensure that it also benefits the health of men, transgender and gender-diverse people and those who are intersex. Third, in working with others in the scientific community to improve methods for sex and gender research, including updating data collection practises, ensuring appropriate statistical analyses and shifting scientific culture to recognise the importance of null findings. By improving focus on these three areas, we see greater potential to translate this research to improve women's health and reduce health inequities for all.

Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank.

Background: Serum lipid traits are associated with cardiovascular disease, but uncertainty remains regarding their associations with dementia. Methods: From 2006 to 2010, 254,575 women and 214,891 men were included from the UK Biobank. Cox regression estimated overall and sex-specific hazard ratios (HRs) for apolipoprotein A (ApoA), apolipoprotein B (ApoB), HDL, LDL, total cholesterol, triglycerides, lipoprotein A, and various lipid ratios, by quarters and standard deviation (SD) higher, associated with all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD). Subgroup analyses by age and social deprivation were conducted. Findings: Over 11·8 years (median), 3734 all-cause dementia (1,716 women), 1231 AD and 929 VaD were recorded. Compared to respective lowest quarters, highest quarter of ApoA was associated with lower dementia risk (HR, [95% confidence interval (95% CI)]: 0·77 [0·69, 0·86]) while the highest quarter of ApoB was associated with greater risk (HR, 1·12 [1·01, 1·24]). Higher HDL/ApoA and ApoB/ApoA, were associated with greater risk of dementia (HR, 1·12 [1·00, 1·25], per standard deviation (SD), 1.23 [1·11, 1·37], per SD, respectively), LDL/ApoB was inversely associated (HR, 0·85 [0·76, 0·94], per SD. Higher triglycerides was associated with higher dementia risk in <60 years, but the inverse was observed for ≥60 years. Similar associations were observed for VaD and AD. Interpretation: Apolipoproteins, and their ratios, were associated with the risk of dementia. It may be prudent to consider apolipoproteins, along with circulating cholesterol, when assessing dementia risk. Funding: University of New South Wales, UK Medical Research Council, and the Australian National Health and Medical Research Council.

Dementia clinical trials over the past decade: are women fairly represented?

Background: Lack of progress in finding disease-modifying treatments for dementia may be due to heterogeneity in treatment effects among subgroups, such as by sex. Therefore, we investigated the characteristics of dementia trials completed in the last decade, with a focus on women's representation and sex-disaggregated outcomes. Methods: Clinical trials on dementia completed since 2010 were identified from ClinicalTrials.gov. Randomised, phase III/IV trials with ≥100 participants were selected to quantify women's representation among participants, by computing the participation to prevalence ratio (PPR) and investigate whether sex-disaggregated analyses had been performed. Results: A total of 1351 trials were identified between January 2010 and August 2021 (429 520 participants), of which 118 were eligible for analysis of women's representation and sex-stratified analysis. Only 113 reported the sex of participants and were included in the analysis of women's representation. Of the 110 469 participants in these 113 trials, 58% were women, lower than their estimated representation in the global dementia population of 64%. The mean PPR was 0.90 (95% CI 0.86 to 0.94). Women's participation tended to be higher when the first or last authors of the trial report were women. Eight out of the 118 trials reported sex-disaggregated outcomes, and three of those found significant sex differences in efficacy outcomes. None of the trials reported screening failures or adverse events stratified by sex. Conclusions: Overall, women and men were equally represented in dementia trials carried out over the past decade, but women's representation was lower than in the underlying dementia population. Sex-disaggregated efficacy and safety outcomes were rarely reported.

Trends of Hypercholesterolemia Change in Shenzhen, China During 1997-2018.

To demonstrate the trends of hypercholesterolemia change in Shenzhen, China from 1997 to 2018. Participants were residents aged 18 to 69 years in Shenzhen, China, and were recruited using multi-stage cluster sampling. All participants were surveyed about their socio-demographics, lifestyle, occupation, mental health, and social support. Physical measurements and blood samples for subsequent measurements were collected according to a standardized protocol. A total of 26,621 individuals participated in the three surveys with 8,266 in 1997, 8,599 in 2009, and 9,756 in 2018. In both women and men, there was a significant downward linear trend in age-adjusted mean high-density lipoprotein-cholesterol (HDL-C) from 1997 to 2018 (women: 0.17 ± 0.06, p = 0.008 vs. men: 0.21 ± 0.04, p < 0.001). In contrast, the age-adjusted total triglycerides and total cholesterol in both sexes have demonstrated an increasing trend in the past two decades. However, no significant changes in age-adjusted low-density lipoprotein-cholesterol (LDL-C) in both men and women between 2009 and 2018 were found (women: 0.00 ± 0.02, p = 0.85 vs. men 0.02 ± 0.03, p = 0.34). The age-adjusted prevalence of hypercholesterolemia observed a rapid rise from 1997 to 2009 and appeared to be stabilized in 2018, which was similar to the trend of the prevalence of high total triglycerides in women. Changes in trends were varied by different types of lipids traits. Over the observed decades, there was a clear increasing trend of prevalence of low HDL-C (<1.04 mmol/L) in both sexes (women: 8.8% in 1997 and doubled to reach 17.5% in 2018 vs. men was 22.1% in 1997 and increased to 39.1% in 2018), particularly among younger age groups. Hence, a bespoke public health strategy aligned with the characteristics of lipids epidemic considered by sex and age groups needs to be developed and implemented.

Sex differences in predictors for cognitive decline and dementia in people with stroke or transient ischemic attack in the PROGRESS trial.

BACKGROUND: Stroke and transient ischemic attack confer greater risk of cognitive decline and dementia. AIMS: We used data from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a blood pressure-lowering randomized controlled trial in stroke/transient ischemic attack. We evaluated overall and sex-specific differences in treatment effects for cognitive decline/dementia, as well as associations with vascular and stroke-specific predictors,considering death as a competing risk. METHODS: Multinomial logistic regression was used to estimate overall and sex-specific odds ratios (OR) (95% confidence intervals (CI)) for treatment effects and predictors associated with the risk of cognitive decline/dementia, and the women-to-men ratio of odds ratio (RORs). RESULTS: Over a median four years, 763 cognitive decline/dementia (30.9% women) were recorded in 5888 participants. Women had lower odds of cognitive decline/dementia than men (OR 0.78, 95%CI 0.63-0.95). Active treatment was associated with lower odds of cognitive decline/dementia (0.84, 0.72-0.98), with no evidence of sex difference. Higher education (0.96,0.94-0.98 (per year)) and baseline Mini-Mental State Examination (MMSE)) were associated with lower odds of cognitive decline/dementia (0.84,0.82-0.86 (per point higher)). Higher diastolic blood pressure (1.11,1.02-1.20 (per 10 mmHg)), low estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (1.27,1.03-1.58), and peripheral arterial disease (1.78,1.26-2.52) were associated with higher odds of cognitive decline/dementia. APOE ɛ4 was not associated with cognitive decline/dementia (1.05 (0.85-1.30)). Low eGFR was more strongly associated with cognitive decline/dementia in women than men (RORs, 1.60 (1.03-2.48)). Diabetes was more strongly associated with men than women. CONCLUSIONS: Several risk factors were associated with cognitive decline/dementia in people with prior stroke/transient ischemic attack, with notable sex differences. Long-term cognitive sequelae of stroke should be considered to strengthen joint prevention strategies for stroke, cognitive decline, and dementia.Trial Registration: This trial was not registered because enrolment began before 1 July 2005.

Prospective associations between depressive symptoms and cognitive functions in middle-aged and elderly Chinese adults.

OBJECTIVE: To examine prospective associations of clinically relevant depressive symptoms with cognitive functions and rates of cognitive decline among Chinese adults aged 45 years and older. METHODS: Data was from the China Health and Retirement Longitudinal Study (CHARLS) with a follow-up of 4 years. Based on the Chinese version of 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), clinically relevant depressive symptoms were defined with a CESD-10 score≥10 points. Cognitive functions were measured in three domains: episodic memory, mental status and global cognition. Linear mixed models were used to assess the associations between clinically relevant depressive symptoms and cognitive functions. RESULTS: A total of 7335 participants (50.10% men; mean age: 57.47) were included in analyses. Participants with clinically relevant depressive symptoms showed poorer episodic memory (ß=-0.35; 95% CI:-0.41, -0.29), mental status (ß=-0.48; 95% CI: -0.57, -0.39), and global cognition (ß=-0.82; 95% CI: -0.94, -0.70) during the follow-up. Compared with counterparts, rates of decline in episodic memory, mental status, and global cognition increased by 0.04 (ß=0.04; 95% CI: 0.02, 0.06), 0.06 (ß=0.06; 95% CI: 0.02, 0.09) and 0.11 (ß=0.11; 95% CI: 0.06, 0.15) units per year in participants with clinically relevant depressive symptoms. LIMITATIONS: A major limitation is that clinically relevant depressive symptoms were assessed by a screening tool and the follow-up was short. CONCLUSION: More severe clinically relevant depressive symptoms were associated with poorer cognitive functions and moderately faster cognitive decline in episodic memory, mental status and global cognition in middle-aged and elderly Chinese adults.

Association between arthritis and depression risk: a prospective study and meta-analysis.

OBJECTIVE: Our research aimed to prospectively evaluate the association between arthritis and depression among middle-aged and elderly Chinese and confirmed this association in other populations. METHODS: Data from the China Health and Retirement Longitudinal Study were analyzed. Participants were enrolled in this study in 2011-2012 (Wave 1) and followed up in 2013-2014 (Wave 2) and 2015-2016 (Wave 3). Depression was defined as having a score equal to over 10 using the Chinese version of 10-item Center for Epidemiological Studies Depression scale. Arthritis was assessed by self-reported physician diagnosis in Wave 1. Cox proportional hazards regression models were fitted to evaluate prospective associations between baseline arthritis status and incident and persistent depression. Summary effect estimates were pooled from our findings and those reported in literature by applying random effects models. RESULTS: The study included 7,386 participants aged 58.48 years (standard deviation, 9.59) for final analyses. Individuals with arthritis had a 35% higher risk (multivariable-adjusted hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 1.23, 1.49) and 50% higher risk (HR: 1.50; 95% CI: 1.22, 1.84) of developing incident and persistent depression compared with those without arthritis. The meta-analysis of prospective studies confirmed increased risk of depression in individuals with arthritis (summary HR: 1.42, 95% CI, 1.34, 1.52). LIMITATIONS: Depression was assessed by a screening tool and arthritis was assessed by self-reported physician diagnosis. CONCLUSIONS: A positive relationship between arthritis and depression was noted in the middle-aged and elderly Chinese adults and other populations.

A Call to Action to Address Sex Differences in Alzheimer Disease Clinical Trials.

This Viewpoint calls for comprehensive investigations into sex differences associated with treatments in existing Alzheimer disease and integration into future Alzheimer disease and related dementia clinical trials.