Neurodegenerative diseases such as dementia and Alzheimer’s disease (AD) have been linked to ocular pathology, particularly thinning of the RNFL, retinal ganglion cell loss and increased optic nerve head cupping. Studies have also identified certain biomolecules commonly found in those with AD in the eyes of patients with open-angle glaucoma (OAG). Following up on these findings, researchers investigated the risk of developing dementia or AD in patients newly diagnosed with OAG and found that these patients are actually at decreased risk compared with the general population.

The retrospective, population-based study included 509 patients with OAG (58.9% female, median age 67.5) from a single county in Minnesota who were followed for over 36 years.

Patient diagnoses were as follows: 54.6% had primary OAG, 15.1% had pseudoexfoliation, 14.1% had treated ocular hypertension, 10.6% had normal-tension glaucoma and 5.5% had pigmentary glaucoma. Over the course of the study, 118 (23%) and 99 (19.4%) of the total patients developed dementia and AD, respectively.

The researchers reported 10-year cumulative probabilities of developing dementia and AD of 12% and 9.9%, respectively. They noted that these observed incidences dementia and AD were significantly lower than the expected population incidence, which was 19% for each.

The investigators reported that the usual comorbid and health risk factors associated with glaucoma weren’t statistical predictors for AD development, but the typical clinical predictors of AD were significant indicators for disease risk. These include level and years of education, history of stroke and past head injury. “Interestingly, older age of onset of OAG was found to be a strong predictor for the development of dementia,” they wrote in their paper.

Those who were diagnosed with OAG at an older age had an approximately 3.5-times greater risk of developing dementia than patients diagnosed at a younger age. “This suggests that although phenotypically comparable, OAG with later onset likely represents a different etiopathogenic entity,” the researchers explained. “Optic nerve head changes in this cohort are possibly occurring as part of more generalized neurodegenerative processes which later clinically manifest as dementia or AD. This would be consistent with the finding of ‘senile sclerotic’ discs in older OAG patients, compared with the steeply excavated discs of younger OAG patients.”

They concluded that OAG patients may be at decreased risk for developing dementia or AD compared with the general population, and that late-onset OAG may be a different etiopathogenic entity similar to neurodegenerative mechanisms in dementia and AD.

Belamkar AV, Mansukhani SA, Savica R, et al. Incidence of dementia in patients with open-angle glaucoma: A population-based study. J Glaucoma. 2021;30:227-34.