194 - Type 2 diabetes and risk of Alzheimer's and vascular dementia: observational and Mendelian randomization studies in >1 million individuals. (ID 1224)
Abstract
Background and Aims
Several large observational studies and meta-analyses have shown that type 2 diabetes is associated with higher risk of dementia. The causal nature of this association remains unanswered.
Methods
In the present nationwide registry study we investigated the associations between type 2 diabetes and Alzheimer’s disease, vascular dementia, unspecified dementia, and all-cause dementia. Further, we tested whether the observational association between type 2 diabetes and Alzheimer’s disease is of a causal nature by applying a two-sample Mendelian randomization strategy. We addressed key biases inherent in Mendelian randomization approaches.
Results
Multifactorial adjusted hazard ratios were 1.13 (1.06-1.21) for Alzheimer’s disease, 1.98 (1.83-2.14) for vascular dementia, 1.53 (1.48-1.59) for unspecified dementia, and 1.48 (1.44-1.53) for all-causes dementia in persons with type 2 diabetes versus without. The two-sample Mendelian randomization estimate for the association between the genetic instrument and Alzheimer’s disease was 1.04 (0.98-1.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias, and weak instrument bias.
Conclusions
In the present study, we showed in the nationwide observational study that type 2 diabetes is associated with Alzheimer’s disease, vascular dementia, unspecified dementia, and all-cause dementia. In a two-sample Mendelian randomization approach using genetic consortia, we found no indication for a causal association between type 2 diabetes and Alzheimer’s disease. The strong observational association between type 2 diabetes and vascular dementia may suggest presence of a causal pathway. However, since no publicly available consortia data exist for vascular dementia, we were unable to test the causal nature of this association.
