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.

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 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.

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.

Serum lipid traits are associated with cardiovascular disease, but uncertainty remains regarding their associations with dementia. 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. 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. 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. University of New South Wales, UK Medical Research Council, and the Australian National Health and Medical Research Council.

The impacts of a changing climate on current and future dementia burdens have not been widely explored. 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. 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. 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.