This retrospective cohort study used TriNetX global data (2005–2025) to assess 10-year risk trajectories of neurodegenerative diseases (MCI, Alzheimer's disease, vascular dementia, unspecified dementias, Parkinson's disease) in 384,256 propensity-matched glaucoma–control pairs, stratified by age onset (<45 vs >65 years) and glaucoma subtype (POAG, PACG, NTG).
Glaucoma was associated with elevated 10-year risks for AD (HR 1.485), vascular dementia (HR 1.213), and Parkinson's disease (HR 1.115, peaking at 10 years); early-onset glaucoma showed a notably high AD risk at 10 years (HR 2.320). By subtype, NTG was the only subtype with a significant Parkinson's disease link (HR 1.283), while AD associations were non-significant across all three individual subtypes.
- Observational design from a real-world database precludes causal inference; associations may reflect shared risk factors or surveillance bias. - ICD-10 code–based outcome ascertainment may undercount or misclassify neurodegenerative diagnoses. - Subtype-level analyses (especially PACG and NTG) likely had smaller sample sizes, reducing power for some comparisons.
Clinicians managing glaucoma patients—especially those with early-onset disease or NTG—should maintain a low threshold for neurocognitive screening, given the observed associations with dementia and Parkinson's disease over 10 years. These findings are correlational, not causal, so they should inform monitoring rather than change treatment targets.
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