Glaucoma Associated With Decreased Cognitive Impairment Risk

Female doctor shows a senior male patient an MRI image of his brain. The doctor is using a digital tablet.
A study shows a number of comorbidities commonly associated with poor health outcomes appear to be protective against dementia and Alzheimer disease.

Patients with open-angle glaucoma (OAG) were less likely to develop dementia compared with the general population, researchers found in a cohort study of residents in Olmsted County, Minnesota, published in Journal of Glaucoma.

While some prior studies have reported an increased risk of dementia in patients with OAG, others have found that these neurodegenerative diseases counteract each other. 

The researchers retrospectively studied all residents diagnosed with OAD from 1965 through 2000, including patients treated for ocular hypertension (OHT). Some patients with pre-perimetric glaucoma had likely been categorized as having OHT in earlier years.

Of the 509 patients included in the study, 278 had primary open-angle glaucoma (POAG), 77 had pseudoexfoliative glaucoma, 72 had treated OHT, 54 had normal tension glaucoma (NTG), and 28 had pigmentary. The researchers found that 118 patients developed dementia, including 99 diagnosed with Alzheimer disease (AD), 11 with vascular dementia, and 4 with combined vascular and AD.

The 10- and 20-year cumulative probability of developing dementia was 12% and 27% and 9.9% and 22.5% for developing AD. In the POAG subgroup, the 10- and 20-year cumulative probability of developing dementia was 10.5% and 22.9%. These probabilities for developing AD were 9.8% and 21.1%.

The 10-year-rate of dementia among patients with OAG (13.0%) was significantly less than among the general population (19.0%), as was the case for AD (OAG 9.9%, general population 19.0%) (P <.001 for all). The 10-year-rate of dementia and AD among patients with POAG (12.0% and 11.0%, respectively; P <.001 for both) and treated OHT was significantly less than expected (6.0%, 6.0%, respectively, P =.02). Observed and expected dementia and AD rates were the same among patients with NTG and pseudoexfoliation glaucoma. No patients with pigmentary glaucoma developed dementia.

In univariate analysis, patients with OAG diagnosed at an older age had a greater risk of developing dementia or AD than those diagnosed when they were younger (hazard ratio (HR): 3.24 per decade of age, HR: 3.47, P <.001 for both), which held in multivariate analysis (HR: 3.31, 95% CI 2.61-4.20) and AD (HR: 3.57, P <.001 for all).

Patients whose highest level of education was primary or secondary education were more likely to develop dementia (HR: 4.10, 3.06) and AD (HR: 4.18, 3.39) compared with those with higher education (dementia HR: 0.87, AD HR: 0.87) (P <.001 for all). Head injury was also a predictor for dementia (HR: 1.98, P =.04) and AD (HR: 2.11, P =.03).  Hypertension remained protective for dementia (HR: 0.40, P <.001) and AD (HR: 0.49, P =.002).

“Univariate and multivariate analysis revealed surprising findings in our data that must be elaborated in the context of the association between glaucoma and AD,” the study says. “Hypertension, hyperlipidemia, diabetes mellitus, and obesity were significantly protective of dementia or AD. These comorbidities are commonly associated with poor health outcomes and are not expected to be protective.”

Since age at onset of glaucoma was a significant predictor for dementia, late-onset OAG may be a different etiopathogenetic entity, the researchers said. The study did not address whether dementia patients may have an increased risk of glaucoma.

Limitations of the study included its retrospective nature and changes in understanding and diagnostic criteria for dementia over the 36 years the study spanned. The population of Olmsted County is also predominantly white, limiting generalizability.


Belamkar AV, Mansukhani SA, Savica R, et al. Incidence of Dementia in Patients With Open-angle Glaucoma: A Population-based Study. J Glaucoma. 2021;30(3):227-234. doi: 10.1097/IJG.0000000000001774