Abstract

The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction=0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

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