Reassessing diabetes and APOE genotype as potential interacting risk factors for Alzheimer’s disease

Objective: To assess whether diabetes alone or in association with Apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s Disease (AD) diagnosis. Methods: A retrospective cohort study of 33,456 participants from the National Alzheimer’s Coordinating Center database. Results: Participants with one or two APOE ε4 alleles had 2.71 (CI:2.55–2.88) and 9.37 (CI:8.14–10.78) times higher odds of AD diagnosis, respectively, relative to those with zero ε4 alleles. In contrast, diabetic participants showed 1.07 (CI:0.96–1.18) times higher odds of AD relative to nondiabetics. Diabetes did not exacerbate the odds of AD in APOE ε4 carriers. APOE ε4 carriage was correlated with declines in long-term memory and verbal fluency, which were strongly correlated with conversion to AD. However, diabetes was correlated with working memory decline, which had a relatively weak correlation with AD. Conclusions: Unlike APOE ε4, there was little evidence that diabetes was a risk factor for AD.