Risk of Dementia in Type 2 Diabetes Patients With Open-Angle Glaucoma: Insights From a Nationwide Real-World Cohort Study.

PURPOSE

To evaluate whether open-angle glaucoma (OAG) serves as a risk marker for subsequent dementia in patients with type 2 diabetes mellitus (T2DM), a population at elevated risk for both conditions.

DESIGN

Retrospective cohort study using longitudinal electronic health record (EHR) data.

PARTICIPANTS

A total of 1,580,368 adults with T2DM from the Merative™ ExplorysTherapeutic Dataset (2010-2022), including 12,405 patients diagnosed with OAG.

METHODS

OAG was treated as a time-dependent exposure in Cox proportional hazards models to account for variable onset timing relative to T2DM diagnosis. The primary outcome was the first recorded diagnosis of all-cause or subtype-specific dementia. Models were adjusted for demographic, clinical, behavioral, and ocular covariates. Kaplan-Meier and subtype-specific time-dependent Cox analyses were performed to evaluate crude and adjusted associations.

MAIN OUTCOME MEASURES

Hazard ratios for incident all-cause and subtype-specific dementia.

RESULTS

Compared to T2DM patients without OAG, those with OAG had significantly reduced dementia-free survival (log-rank p < .001). After covariate adjustment, OAG was associated with a 13% increased risk of all-cause dementia (HR = 1.13, 95%

CI

1.09-1.17). Subtype-specific analysis revealed elevated risks for vascular (HR = 1.37, 95%

CI

1.08-1.74) and frontotemporal dementia (HR = 1.39, 95%

CI

1.06-1.82), but no evidence of increased risk for Alzheimer's disease (HR = 0.63, 95%

CI

0.52-0.76). Stroke and depression were also strong independent risk factors.

CONCLUSIONS

In patients with T2DM, OAG was associated with an increased risk of non-Alzheimer's dementia, particularly vascular and frontotemporal types. These findings support the hypothesis of shared neurovascular mechanisms and highlight the potential of ophthalmic assessments for early dementia risk stratification in high-risk populations.