Comorbidities and apolipoprotein E genotypes of patients with mild cognitive impairment in transition to Alzheimer's disease.

Background: Three common chronic diseases in the elderly: diabetes, hypertension, and hypercholesterolemia, associate with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Objective: We will examine the association of apolipoprotein E (APOE) ε4 allele, diabetes, hypertension, and hypercholesterolemia (in combination) with the transition of MCI to AD.

Methods: We examine patients from the National Alzheimer's Coordinating Center database from June 2005 to May 2021. AD converted from MCI, stable MCI, and non MCI/AD control subjects were analyzed using Cox proportional hazard models with propensity score weights on matching demographic information and medications prescribed at baseline.

Results: With MCI time of diagnosis as the index date, MCI patients with diabetes and hypertension carried a higher risk of developing AD (HR = 1.17, 95%CI (1.04, 1.31), p = 0.01) compared to MCI patients with a single condition. A similar observation was found among MCI patients with diabetes and hypercholesterolemia (HR = 1.20, 95%CI (1.07, 1.36), p = 0.002). Compared to MCI patients who had a single condition and without APOE ε4 allele, MCI patients with APOE ε4/4 and both diabetes and hypertension have a significantly higher risk of AD onset (HR = 7.6, 95%CI (5.02, 11.5), p < 0.0001). Those with APOE ε3/4 also have a significantly high risk (HR = 2.3, 95%CI (1.92, 2.75), p < 0.0001). Comparable outcomes were found among those with diabetes and hypercholesterolemia.

Conclusions: The combination of diabetes with hypertension or hypercholesterolemia have a significant association with the progression of MCI to AD, and APOE ε4 allele enhances the association of these selected comorbidities in promoting this conversion.