Glaucoma and Neurodegenerative Disease Risk: A 10-Year Assessment of Real-World Global Data.
Glaucoma and Neurodegenerative Disease Risk: A 10-Year Assessment of Real-World Global Data.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Taipei, TW · Author affiliation
From the Department of Medical Education (M.S.W.), National Taiwan University Hospital, Taipei, Taiwan.Location evidence
New Taipei City, TW · Author affiliation
Department of Research (J.W.), Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Biomedical Sciences (J.W.), Queensland University of Technology, Brisbane, Australia.Location evidence
Brisbane, AU · Author affiliation
Department of Research (J.W.), Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Biomedical Sciences (J.W.), Queensland University of Technology, Brisbane, Australia.Location evidence
Kaohsiung, TW · Author affiliation
Cheng Ching Eye Center (C-W.W.), Kaohsiung City, Taiwan.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
PURPOSE: To evaluate 10-year risk trajectories of newly diagnosed neurodegenerative diseases among glaucoma patients across age-stratified cohorts and clinical subtypes. DESIGN: Retrospective cohort study. METHODS: Using TriNetX data (2005-2025), glaucoma patients were propensity-matched 1:1 to controls based on baseline demographics, comorbidities, medications, and laboratory metrics. Outcomes were defined using International Classification of Diseases, Tenth Revision codes. Risks for mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VD), unspecified dementias, and Parkinson's disease (PD) were assessed. Cohorts were stratified by age (<45 vs >65 years) and subtype (primary open-angle [POAG], primary angle-closure [PACG], and normal-tension [NTG] glaucoma). MAIN OUTCOME MEASURES: 1-, 3-, 5-, and 10-year hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 384,256 matched pairs, glaucoma correlated with elevated 10-year risks for AD (HR = 1.485; 95% CI,1.427-1.546; P < .001), VD (HR = 1.213; 95% CI, 1.159-1.27; P < .001), and a delayed PD risk peaking at 10 years (HR = 1.115; 95% CI, 1.066-1.167; P < .001). AD and VD risks emerged early in late-onset glaucoma but showed delayed emergence in early-onset patients, where AD risk peaked at 10 years (HR = 2.320; P = .03). Subtype analysis revealed no significant AD associations for POAG (HR = 1.044; P = .10), PACG (HR = 1.096; P = .13), or NTG (HR = 1.097; P = .19). However, VD risk was elevated in POAG (HR = 1.203; 95% CI, 1.129-1.281; P < .001) and PACG (HR = 1.224; 95% CI, 1.056-1.419; P = .007), but not NTG (P = .08). MCI risk increased in POAG (HR = 1.201; 95% CI, 1.120-1.288; P < .001) and NTG (HR = 1.235; 95% CI, 1.089-1.401; P = .001). NTG demonstrated the only significant PD association (HR = 1.283; 95% CI, 1.043-1.577; P = .018), while POAG (P = .05) and PACG (P = .58) showed no correlation. All 3 subtypes maintained significant associations with unspecified dementia (all P < .05). CONCLUSIONS: Glaucoma is observationally associated with subsequent neurodegenerative diagnoses, with statistical trajectories varying by onset age and clinical subtype. These findings indicate population-level correlations rather than causal mechanistic linkages.