Time‐dependent impact of type 2 diabetes mellitus on incident prodromal Alzheimer disease: A longitudinal study in 1395 participants

Abstract Background and purpose This study was undertaken to investigate the longitudinal impact of type 2 diabetes mellitus (T2DM) on the prodromal and dementia stages of Alzheimer disease (AD), focusing on diabetes duration and other comorbidities. Methods A total of 1395 dementia‐free individuals aged 55–90 years with maximum 15‐year follow‐up data were enrolled from the Alzheimer's Disease Neuroimaging Initiative database. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of the incidence of prodromal or dementia stages of AD. Results Longer T2DM duration (≥5 years; multiadjusted HR = 2.19, 95% confidence interval [CI] = 1.05–4.58), but not shorter T2DM duration (<5 years), was associated with a significantly increased risk of incident prodromal AD over a mean follow‐up of 4.8 years. APOE ε4 allele (HR = 3.32, 95% CI = 1.41–7.79) and comorbid coronary artery disease (CAD; HR = 3.20, 95% CI = 1.29–7.95) further increased the risk of incident prodromal AD in patients with T2DM. No significant association was observed between T2DM and the risk of progression from prodromal AD to AD dementia. Conclusions T2DM, which is characterized by a longer duration, increases the incidence risk of prodromal AD but not AD dementia. APOE ε4 allele and comorbid CAD strengthen the relationship between T2DM and prodromal AD. These findings highlight T2DM characteristics and its comorbidities as predictors for accurate prediction of AD and screening of at‐risk populations.