Primary open-angle glaucoma as a marker of upcoming Alzheimer's disease: A 20-year Danish National Registry-Based...

To investigate whether primary open-angle glaucoma (POAG) is associated with an increased long-term risk of developing Alzheimer's disease, given its shared neurodegenerative features.

A 20-year longitudinal, registry-based matched cohort study was conducted using Danish national health registries from 1998 to 2018. Individuals aged 65 years or older with POAG identified by registration with the diagnostic code (ICD-10 = H40.1*) or at least four redeemed glaucoma prescriptions (ATC = S01E*) within 1 year entered the cohort. Each individual with POAG was randomly matched with five controls of the same sex and birth year. The outcome of Alzheimer's disease was defined by registration with the diagnostic code (ICD-10 = G30*, F00*). A Cox regression model adjusting for age, sex and systemic comorbidities estimated the hazard ratio (HR) for Alzheimer's disease and a Fine-Grey competing-risk model accounted for death as a competing event.

The study included 61 829 individuals with POAG and 306 794 matched controls (42.63% males, 57.37% females; median age 75.22 years, IQR: 70.35-80.63). Alzheimer's disease developed in 1.61% of individuals with POAG and 1.59% of controls. POAG did not appear to increase the risk of Alzheimer's disease (adjusted HR 0.98, 95% CI: 0.93-1.03). Competing risk analyses found a slightly increased risk of Alzheimer's disease observed among men with POAG (sHR 1.12, 95% CI: 1.03-1.21), whereas no association was found among women (sHR 1.00, 95% CI: 0.94-1.07).

In this nationwide matched cohort study, POAG was not clearly associated with an overall increased risk of developing Alzheimer's disease over 20 years.