Investigating the Relationship Between Type 2 Diabetes and Dementia Using Electronic Medical Records in the GoDARTS Bioresource

Objective: To investigate the impact of type 2 diabetes on incidence of major dementia subtypes, Alzheimer and vascular dementia, using electronic medical records (EMR) in the GoDARTS bioresource.

Research Design and Methods: GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) comprises a large case-control study of type 2 diabetes with longitudinal follow-up in EMR. Dementia case subjects after recruitment were passively identified in the EMR, and using a combination of case note review, an Alzheimer-specific weighted genetic risk score (wGRS), and APOE4 genotype, we validated major dementia subtypes. We undertook a retrospective matched cohort study to determine the risk of type 2 diabetes status for incident dementia accounting for competing risk of death.

Results: Type 2 diabetes status was associated with a significant risk of any dementia (causespecific hazard ratio [csHR] 1.46, 95% CI 1.31-1.64), which was attenuated, but still significant, whencompeting risk of death was accounted for (subdistribution [sd]HR 1.26, 95% CI 1.13-1.41). The accuracy of EMR-defined cases of Alzheimer or vascular dementia was highdpositive predictive value (PPV) 86.4% and PPV 72.8%, respectivelydand wGRS significantly predicted Alzheimer dementia (HR 1.23, 95% CI 1.12-1.34) but not vascular dementia (HR 1.02, 95% CI 0.91-1.15). Conversely, type 2 diabetes was strongly associated with vascular dementia (csHR 2.47,95%C1.92-3.18) but not Alzheimer dementia, particularly after competing risk of death was accounted for (sdHR 1.02, 95% CI 0.87-1.18).

Conclusions: Our study indicates that type 2 diabetes is associated with an increased risk of vascular dementia but not with an increased risk of Alzheimer dementia and highlights the potential value of bioresources linked to EMR to study dementia.