Longitudinal Assessment of Age-Related Macular Degeneration and Risk of Dementia Using Clinical Setting Data

To examine whether there is an association between age-related macular degeneration (AMD) and dementia using a large, multi-institutional clinical data.

A retrospective cohort study.

Patients with AMD, including both neovascular AMD (nvAMD) and non-neovascular AMD (non-nvAMD) types, along with matched controls who had a record of eye examination but no diagnosis of AMD.

Data were extracted from the 3 largest TriNetX networks (Global, United States, and Europe, Middle East, and Africa [EMEA]). Dementia diagnoses (Alzheimer disease [AD], vascular dementia, and unspecified dementia) and dementia-related medication use were compared between AMD and non-AMD groups. Diagnoses were identified using International Classification of Diseases, 10th Revision codes. Survival analyses were performed using Kaplan-Meier curves, and hazard ratios (HRs) were estimated using Cox proportional hazards models across 5-, 7-, and 10-year follow-up periods.

Hazard ratios for dementia subtypes in AMD patients versus non-AMD patients and in nvAMD patients versus non-nvAMD patients.

No significant association between AMD and AD was observed in the global network. In the United States, AMD was associated with a reduced risk of AD at 5 and 7 years (HR = 0.79 and 0.75; P < 0.0001), but not at 10 years. In the EMEA cohort, a protective association emerged at 7 and 10 years (HR = 0.16 and 0.33; P = 0.0063 and 0.0265). Vascular dementia showed no global association but was reduced in the United States at 5 and 7 years (HR = 0.73 and 0.79; P < 0.0001 and 0.0003). Unspecified dementia was associated with increased risk globally (HR = 1.17-1.27; P ≤ 0.0016), while the US data indicated a protective trend at 5 and 7 years. Dementia medication use was elevated in the global network at 7 years (HR = 1.27, P < 0.0001), but lower in the United States across all time points (P < 0.01). The negative control outcome (appendicitis) showed no difference between groups. No significant differences in AD or vascular dementia were found between nvAMD and non-AMD patients, although unspecified dementia and dementia medication use were lower in the nvAMD group.

Age-related macular degeneration was not consistently positively associated with AD or vascular dementia across networks. Regional variation, particularly negative associations in the United States, suggests underlying health care or diagnostic differences.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.