Glycemic status, early-onset and late-onset dementia, dementia-free lifespan, and brain structure: A population-based cohort study

To evaluate associations of glycemic status with incident early-onset dementia (EOD) and late-onset dementia (LOD), dementia-free life expectancy, brain MRI structure measures, as well as the mediation pathway of depressive episode METHODS: A population-based cohort study based on UK Biobank, enrolling a total of 286 743 (mean [SD] age, 51.5 [5.9] years) and 330 103 participants (mean [SD] age, 60.7 [5.0] years) for analyzing EOD and LOD, respectively. Incident EOD was defined as dementia diagnosis before age 65, and LOD defined as dementia after age 65. Diabetes participants with optimal glycemic control respectively had a 47 % lower EOD incidence and a 17 % lower LOD incidence, up to 3.2 years longer dementia-free lifespan at age 50, and better dementia-related brain structure measures, compared to counterparts with worse glycemic status. Incident depressive episode mediated 18.8 % (P = 0.014) and 7.8 % (P < 0.001) of associations between glycemic status with EOD and LOD, respectively. Better glycemic status was associated with reduced EOD and LOD risks, prolonged dementia-free lifespan, and brain MRI measures, partiality mediated by depressive episode. These findings support the potential significance of reaching ideal glycemic status to prevent dementia onset and prolong dementia-free longevity at the early pre-symptomatic stage in young diabetes.