POAG Not Clearly Associated with Risk of Developing Alzheimer's Over 20 Years

Despite the lack of a strong association in this study, a biological link between POAG and Alzheimer's disease remains plausible and is worthy of further exploration in future research. Photo: Michael Dorkowski, OD. Click image to enlarge. Previous research revealed a potential association between glaucoma and the development of cerebral neurodegenerative conditions such as Alzheimer’s disease. Given the shared pathophysiology of both conditions, researchers of a 20-year study investigated whether primary open-angle glaucoma (POAG) is associated with an increased long-term risk of developing Alzheimer's. No clear overall association was observed; however, when accounting for death as a competing risk, a small increased risk of Alzheimer’s was found among men with POAG. The findings were reported in Acta Ophthlamologica.This longitudinal, registry-based matched cohort study was conducted using Danish national health registries from 1998 to 2018. The authors noted that this is among the largest cohort studies published examining the association between POAG and Alzheimer’s disease, as it included individuals aged 65 years or older—61,829 with POAG and 306,794 matched controls (42.63% men, 57.37% women). Each individual with POAG was randomly matched with five controls of the same sex and birth year.Alzheimer’s developed in 1.61% of individuals with POAG and 1.59% of controls, but POAG did not appear to increase the risk of Alzheimer's. Competing risk analyses found a slightly increased risk of the disease observed among men with POAG, whereas no association was found among women. While the study was statistically robust, the authors wrote that this finding should primarily be viewed as an indicator of a potential link rather than a clinically important risk elevation.Despite the lack of a strong association in this study, a biological link between POAG and Alzheimer’s remains plausible, they maintain, as both conditions involve neurodegeneration and share overlapping pathological features, such as abnormal aggregation of β-amyloid and tau protein. “Given that the retina is considered an extension of the central nervous system, it is possible that retinal changes in glaucoma reflect neurodegenerative processes similar to those seen in Alzheimer's disease,” the authors explained in their paper.One of the strengths of this study was its incorporation of a competing risk analysis, which accounted for the high mortality rates in this elderly population. This ensured that the associations between POAG and Alzheimer’s were not overestimated due to deaths occurring before the development of the disease. Important confounders, such as comorbidities, age and sex, also strengthened the validity of the analyses. However, the authors noted that other unmeasured elements, such as lifestyle factors, genetic predispositions and socioeconomic conditions, could influence the observed associations and contribute to differences seen across countries.“Moreover, in large register-based studies, even small increases in risk may reach statistical significance due to the high statistical power provided by very large sample sizes,” the authors wrote in their paper. “In this context, the observed 12% increased risk of Alzheimer’s disease among men should be interpreted with caution. Although the association remained statistically significant after accounting for the competing risk of death, its magnitude is modest and unlikely to represent a clinically meaningful difference at the individual level.”This sex-specific difference may point to underlying biological mechanisms that differ between men and women, however, warranting further research to explore this possible link, as well as the shared neurodegenerative features of POAG and Alzheimer’s disease.Click here for the journal source. Kronvold C, Sperling S, Moller S, et al. Primary open-angle glaucoma as a marker of upcoming Alzheimer’s disease: a 20-year Danish National Registry-based study. Acta Ophthalmologica. November 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.