Mendelian randomization study of diabetes and dementia in the Million Veteran Program

Abstract

INTRODUCTION: Diabetes and dementia are diseases of high healthcare burden worldwide. Individuals with diabetes have 1.4 to 2.2 times higher risk of dementia. Our objective was to evaluate evidence of causality between these two common diseases. METHODS: We conducted a one-sample Mendelian randomization (MR) analysis in the U.S. Department of Veterans Affairs Million Veteran program. The study included 334,672 participants at least 65 years of age with type 2 diabetes and dementia case-control status and genotype data. RESULTS: For each standard deviation increase in genetically-predicted diabetes, we found increased odds of three dementia diagnoses in non-Hispanic White participants (all-cause: OR=1.07[1.05-1.08],P=3.40E-18; vascular: OR=1.11[1.07-1.15],P=3.63E-09, Alzheimers: OR=1.06[1.02-1.09],P=6.84E-04) and non-Hispanic Black participants (all-cause: OR=1.06[1.02-1.10],P=3.66E-03, vascular: OR=1.11[1.04-1.19],P=2.20E-03, Alzheimers: OR=1.12 [1.02-1.23],P=1.60E-02) but not in Hispanic participants (all P>.05). DISCUSSION: We found evidence of causality between diabetes and dementia using a one-sample MR study, with access to individual level data, overcoming limitations of prior studies utilizing two-sample MR techniques.

Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross‐sectional study with 2020 participants

“…Previous studies investigating diabetes and VaD correlation were also consistent with the results. Studies analyzing data from databases in the United States, Denmark, Switzerland, and the United Kingdom all found a positive correlation between diabetes and VaD (Celis‐Morales et al., 2022; Litkowski et al., 2023; Thomassen et al., 2020; Wang et al., 2023). However, the study aimed the association between diabetes and VaMCI was few.…”