The study was conducted by Yuto Yoshida from the Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan, and colleagues. While glaucoma is primarily known as an eye disorder characterized by progressive optic nerve damage, growing evidence points to shared neurodegenerative mechanisms with Alzheimer’s disease. However, data specifically examining its relationship with early-onset Alzheimer’s disease have been limited.
To explore this association, the researchers performed a large case-control analysis using data from a nationwide Japanese administrative claims database covering the period from 2006 to 2022. The study focused on adults aged 40 to 64 years, an age group relevant for early-onset Alzheimer’s disease. A total of 2,344 individuals with EOAD were identified based on a diagnosis of Alzheimer’s disease along with prescriptions for Alzheimer’s medications. These patients were matched in a 4:1 ratio by age and sex with 9,376 control participants without Alzheimer’s disease. The mean age across both groups was 58 years, and just over half of the participants were men.
Exposure to open-angle glaucoma was defined as having received an OAG diagnosis at least 12 months before the index date, which was the first prescription of Alzheimer’s medication. Using conditional logistic regression, the investigators assessed the association between prior OAG and the risk of EOAD, while also examining the role of other comorbidities.
The researchers reported the following findings:
- Open-angle glaucoma was more common in patients with early-onset Alzheimer’s disease (16%) than in controls (12.5%).
- Open-angle glaucoma was linked to a 22% higher risk of early-onset Alzheimer’s disease.
- The association between glaucoma and early-onset Alzheimer’s disease was significant in men but not in women.
- Depression showed the strongest association with early-onset Alzheimer’s disease.
- Excessive alcohol use, diabetes, and hypertension were also significantly associated with early-onset Alzheimer’s disease.
- No significant association was observed between early-onset Alzheimer’s disease and dyslipidemia, hearing loss, or obesity.
The authors emphasized that while the increased risk associated with OAG was modest, it remains clinically relevant given the shared neurodegenerative features of glaucoma and Alzheimer’s disease. They suggested that individuals diagnosed with open-angle glaucoma, particularly middle-aged men, may benefit from closer observation for early cognitive symptoms.
“In conclusion, individuals with OAG exhibit a modestly increased risk of developing early-onset Alzheimer’s disease and should be monitored for cognitive symptoms to facilitate early detection and timely intervention,” the investigators noted. They also cautioned that further research is needed to clarify the biological mechanisms underlying this association and to determine whether targeted screening strategies could improve outcomes for patients at risk.
Reference:
Yoshida, Y., Michihata, N., Tanito, M., Hiratsuka, Y., Nakao, S., & Yasunaga, H. (2025). Association between open angle glaucoma and early onset Alzheimer's disease. Journal of Alzheimer’s Disease. https://doi.org/10.1177/13872877251410501
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