Glaucoma Diagnosis Linked to Increased Alzheimer’s Risk

Previous studies have pointed to optineurin as a common shared genetic risk factor for Alzheimer’s and normal-tension glaucoma. Both primary open-angle and normotensive glaucoma were associated with Alzheimer’s in this study. Photo: Julia Reimold, OD, and Chris Wroten, OD. Click image to enlarge. Both glaucoma and Alzheimer’s disease are in the neurodegenerative disorder category, and it’s possible that shared mechanisms may exist between the two. Researchers are trying to better understand exactly what relationship exists. Glaucoma and dementia have already been shown to be related in some way, but in a new paper published in Ophthalmology, investigators specifically parse out whether certain glaucoma and dementia subtypes are related to each other.In a retrospective investigation, incidence of dementia and its subtypes across APOE genotypes in glaucoma patients was observed via data from the All of Us Research Program from the NIH. Using electronic health records, every person with glaucoma was matched with four controls; propensity score matching considered age, race, ethnicity and sex. Included for analysis were 9,444 individuals with glaucoma diagnoses (excluding those with a pre-existing dementia diagnosis) and 37,776 matched controls. During the observation period (median 6.5 years), 2.4% of individuals were diagnosed with dementia.Glaucoma was linked to significantly increased risk of all-cause dementia (adjusted hazard ratio [HR]: 1.23), Alzheimer’s disease (HR: 1.60) and vascular dementia (HR: 1.38). Among subtypes, primary open-angle glaucoma (POAG; n=5,756) and normal-tension glaucoma (n=1,106) were both found to have increased risk of Alzheimer’s disease, with HRs of 1.48 and 1.87, respectively. Conversely, angle-closure glaucoma (n=3,150) showed no significant association (HR: 1.49) with Alzheimer’s specifically. All-cause dementia was found to be of greater risk in those with glaucoma spanning all three APOE genotypes; greatest increased risk occurred with the e2/e2 genotype (n=4,965) with an HR of 1.76, followed by e3/e3 (n=23,667) and an HR of 1.45 and finally e3/e4 (n=8,544) with an HR of 1.43.When elaborating on their findings, the study authors write that “the greatest statistical strength being in the association between POAG and Alzheimer’s disease and the past literature on how POAG and Alzheimer’s disease share neurodegenerative mechanisms in common support that the overlap between glaucoma and dementia risk is most strongly driven by POAG and Alzheimer’s disease.”Even further, they suggest that these “associations are not driven purely by the vision loss that is shared across subtypes of glaucoma but share common risk factors or disease mechanisms.”However, the investigators do point out that “the data cannot yet comment on whether APOE genotype modifies the relationship between subtypes of glaucoma—POAG in particular—and Alzheimer’s disease risk nor can the data comment on the relationship between glaucoma and dementia risk in individuals with e2/e2 and e4/e4 genotypes since the rarity of the e2/e2 and e4/e4 genotypes, each comprising <1% to 3% of the population.”Click here for the journal source. Pham K, Salowe R, Di Rosa I, et al. The association between glaucoma and dementia in a national cohort of All of Us participants. Ophthalmology. September 15, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.