Global, Regional and National burden of dementia attributable to metabolic dysregulation from 1990 to 2021, with projections of burden to 2050: An analysis of the global burden of disease study 2021.

Background

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Aims

We quantified dementia burden attributable to high fasting plasma glucose (FPG) and high body mass index (BMI), projected trends to 2050, and examined metabolic traits using Mendelian randomization (MR).

Methods

Global Burden of Disease (GBD) 2021 data from 204 countries and territories were analyzed by age, sex, and Socio-demographic Index. Future burden was projected using time-series and Bayesian age-period-cohort models. Two-sample MR used European-ancestry genetic summary data with inverse-variance weighted estimates and sensitivity analyses.

Results

Metabolic-attributable dementia burden increased, with a steeper rise for high BMI than high FPG. Genetically predicted hypertension was associated most clearly with vascular dementia (odds ratio 2.72, 95% confidence interval 1.66-4.45; P = 0.0001) and was supported by the weighted-median estimator. Genetically predicted high-density lipoprotein cholesterol (HDL-C) showed only a nominal association with Alzheimer disease (odds ratio 1.09, 95% confidence interval 1.00-1.19; P = 0.0459) that was not consistently supported across MR methods. Mediation analyses were not significant.

Conclusions

Metabolic-attributable dementia burden is increasing globally. High BMI was a prominent contributor in GBD analyses, whereas MR most strongly supported hypertension and vascular dementia. The HDL-C finding is exploratory, and MR does not directly validate the BMI or FPG burden estimates.