Background Given the projected trends in population ageing and population growth, the number of people with dementia is expected to increase. In addition, strong evidence has emerged supporting the importance of potentially modifiable risk factors for dementia. Characterising the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritisation. This study aimed to improve on previous forecasts of dementia prevalence by producing country-level estimates and incorporating information on selected risk factors. MethodsWe forecasted the prevalence of dementia attributable to the three dementia risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (high body-mass index, high fasting plasma glucose, and smoking) from 2019 to 2050, using relative risks and forecasted risk factor prevalence to predict GBD risk-attributable prevalence in 2050 globally and by world region and country. Using linear regression models with education included as an additional predictor, we then forecasted the prevalence of dementia not attributable to GBD risks. To assess the relative contribution of future trends in GBD risk factors, education, population growth, and population ageing, we did a decomposition analysis. FindingsWe estimated that the number of people with dementia would increase from 57•4 (95% uncertainty interval 50•4-65•1) million cases globally in 2019 to 152•8 (130•8-175•9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0•1% [-7•5 to 10•8]). We estimated that there were more women with dementia than men with dementia globally in 2019 (female-to-male ratio of 1•69 [1•64-1•73]), and we expect this pattern to continue to 2050 (female-to-male ratio of 1•67 [1•52-1•85]). There was geographical heterogeneity in the projected increases across countries and regions, with the smallest percentage changes in the number of projected dementia cases in high-income Asia Pacific (53% [41-67]) and western Europe (74% [58-90]), and the largest in north Africa and the Middle East (367% [329-403]) and eastern sub-Saharan Africa (357% [323-395]). Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected incr...

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Introduction Incidence estimates of mild cognitive impairment (MCI) range widely. We obtained contemporary age‐specific MCI incidence rates and examined sources of heterogeneity. Methods We conducted a systematic review of population‐based studies from the Americas, Europe, and Australia using restrictive inclusion criteria to limit heterogeneity. Incidence was examined using 5‐year age categories for MCI and amnestic/nonamnestic subtypes. Data were synthesized using quantitative and qualitative descriptive analyses and quantitative meta‐analyses. Results Meta‐analysis estimates (95% CI) of MCI incidence per 1000 person‐years were 22.5 (5.1–51.4) for ages 75–79y, 40.9 (7.7–97.5) for ages 80–84y, and 60.1 (6.7–159.0) for ages 85+y. Despite restrictive inclusion criteria, considerable heterogeneity (measured by I2) remained. Meta‐analysis findings and simple descriptive statistics were consistent and supported by qualitative review. Discussion Heterogeneity in MCI incidence estimates persisted across age‐specific estimates from population samples, likely reflecting differences in populations and methods. Incidence rate ranges are important to consider with summary point estimates.

Tumorigenesis is a multistep process in which oncogenes play a key role in tumor formation, growth, and maintenance. MET was discovered as an oncogene that is activated by its ligand, hepatocyte growth factor. Deregulated signaling in the c-Met pathway has been observed in multiple tumor types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.

Introduction Clinical trials involving patients with Alzheimer's disease (AD) continue to try to identify disease‐modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods A systematic review sought research that elicited information from people with AD, their caregivers, and health‐care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.