Risk of Alzheimer's Disease and Related Dementias in Persons with Glaucoma

Purpose Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks following glaucoma diagnosis in a large population-based cohort. Design National matched cohort study. Participants 324,730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3,247,300 age- and sex-matched population-based controls without prior dementia. Methods Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities. Main Outcome Measures AD, VaD, and all-cause dementia, identified from nationwide inpatient and outpatient diagnoses through 2018. Results In 16 million person-years of follow-up, 32,339 (10%) persons with glaucoma and 226,896 (7%) controls were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% CI, 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥70 and were not elevated for ages <60 years. Conclusions In this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment.