TOPLINE: 

Compared with people without glaucoma, those diagnosed with the condition had a 23% higher risk of developing dementia, and were at increased risk for both Alzheimer's disease and vascular dementia. These associations persisted across subtypes of glaucoma and apolipoprotein E (APOE) genotypes. 

METHODOLOGY:

• Researchers conducted a retrospective longitudinal cohort study to assess the risk for incident dementia and its subtypes in patients with glaucoma, with the subtypes of glaucoma assessed including primary open-angle, normal-tension, and angle-closure forms of the eye condition.
• They identified 9444 individuals with glaucoma and matched them with 37,776 control individuals without the condition on the basis of age, race, ethnicity, and sex; those diagnosed with dementia prior to glaucoma were excluded from the analysis.
• This study also leveraged whole genome sequencing data from the dataset to stratify the association between glaucoma and dementia by APOE genotype — the strongest genetic risk factor for Alzheimer's disease — and matched patients with glaucoma to control individuals on the basis of genetic similarity.
• The following genotypes of APOE were analyzed: epsilon 2/epsilon 2, epsilon 2/epsilon 3, epsilon 2/epsilon 4, epsilon 3/epsilon 3, epsilon 3/epsilon 4, and epsilon 4/epsilon 4.
• The median follow-up duration was 6.5 years.

TAKEAWAY:

• Patients with glaucoma had significantly higher risks for all-cause dementia (adjusted hazard ratio [aHR], 1.23; 95% CI, 1.08-1.40), Alzheimer's disease (aHR, 1.60; 95% CI, 1.26-2.02), and vascular dementia (aHR, 1.38; 95% CI, 1.04-1.83) than control individuals.
• Both primary open-angle glaucoma and normal-tension glaucoma were significantly linked to an increased risk for Alzheimer's disease (aHR, 1.48; 95% CI, 1.11-1.96 and aHR, 1.87; 95% CI, 1.09-3.18, respectively); angle-closure glaucoma was associated with an increased risk for dementia (aHR, 1.31; 95% CI, 1.03-1.67).
• Analysis across APOE genotypes revealed the greatest increase in risk for all-cause dementia in epsilon 2/epsilon 3 carriers (aHR, 1.76; 95% CI, 1.11-2.79), followed by epsilon 3/epsilon 3 (aHR, 1.45; 95% CI, 1.19-1.75) and epsilon 3/epsilon 4 (aHR, 1.43; 95% CI, 1.09-1.87) carriers.

IN PRACTICE:

“Glaucoma was associated [with] an increased risk of dementia using a demographically matched control cohort and adjusting for comorbidities. Our results align with previous meta-analyses that demonstrated an association between glaucoma and dementia risk ," the researchers reported.

SOURCE:

The study was led by Kenneth Pham, BA, of the Department of Ophthalmology at the University of Pennsylvania Perelman School of Medicine, in Philadelphia. It was published online on September 15, 2025, in Ophthalmology.

LIMITATIONS:

The study relied on self-reported healthcare access due to which cases of glaucoma and dementia may have been missed. Limited eye care access among some study participants also may have led to underdiagnosis or misdiagnosis of glaucoma. The study was also limited by a short duration of follow-up. 

DISCLOSURES:

The study received support from the National Eye Institute, Vision Research Core Grant, and other sources. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.