January is Glaucoma Awareness Month, a good time to take a look at recently published research from the field. A forthcoming study in the Journal of Alzheimer’s Disease uses data from a prospective cohort study called Adult Changes in Thought (ACT), which follows cognitively normal older adults until Alzheimer’s disease and related dementia development. Those included in the group were study participants with a diagnosis of glaucoma who filled prescriptions for glaucoma medications (including alpha-adrenergic agonists, beta-adrenergic antagonists, miotics, carbonic anhydrase inhibitors, and prostaglandins) for at least ten years.
Davidson et al. cite sensory impairment as one modifiable potential source of dementia risk. Glaucoma is a common cause of visual impairment in older adults, and several past studies have suggested glaucoma may be associated with a higher risk of dementia, although this is not yet proven. Additionally, glaucoma and dementia may potentially share molecular pathways and clinical features which are associated with neurodegeneration.
Treatment of glaucoma focuses on reduction of intraocular pressure through daily use of topical eye drops. Because both glaucoma and dementia are highly prevalent in older adults, therefore Davidson et al. feel it is important to study the potential connections between the two.
Patients included in this study are older adults at risk of dementia from Kaiser Permanente Washington (state). Participants are followed by ACT until they develop Alzheimer’s disease and related dementia. The study looked at age and dementia risk, first glaucoma medication fill, in addition to other factors. 521 participants in the ACT study were ultimately included in this analysis. 62% were female, and beta-adrenergic antagonists were the most frequently prescribed type of medication. The mean exposure time for each study participant to beta-adrenergic antagonists was 1.4 years.
The study concluded that with each year of alpha-adrenergic agonists (AAA), there was a 33% higher risk of dementia (but not Alzheimer ’s-type dementia). The findings of Davidson et al showed that beyond AAA, there was no other glaucoma medication class associated with dementia or Alzheimer’s-type dementia. This constitutes a new finding, because exposure to glaucoma medication use has not been studied extensively, nor has use of AAA previously been linked to an increased risk of dementia. It is important to note that some studies have also pointed to adrenergic dysregulation as playing a role in cognitive decline. Topical use of AAA drops induces central adrenergic activity in some patients, which the authors hypothesize could be a mechanism leading to adrenergic dysregulation.
The authors note that their findings were unexpected, and they cannot fully rule out that the association between AAA glaucoma medication and dementia is related to patients who have more severe glaucoma. (Data on the severity of the glaucoma was unavailable to researchers.) AAA was not a first-line medication, but rather one prescribed to patients after beta blockers or prostaglandins are unsuccessful. In the cohort being studied, AAA was the third most prescribed medication for glaucoma.
While Davidson et al. acknowledge study limitations, this finding indicates an important area for future research, to look at medication exposure time and other factors such as other drugs patients have been taking concurrently with glaucoma medications.
References
Davidson, O., Lee, M. L., Kam, J. P., Brush, M., Rajesh, A., Blazes, M., Arterburn, D. E., Duerr, E., Gibbons, L. E., Crane, P. K., Lee, C. S., & Eye ACT study group (2025). Associations between dementia and exposure to topical glaucoma medications. Journal of Alzheimer's disease: JAD, 13872877241305745. Advance online publication. https://doi.org/10.1177/13872877241305745