Herpes Zoster Ophthalmicus and 3-Year Dementia Risk: Association and Modification by Prior Zoster Vaccination in a...

To compare 3-year incident dementia risk in adults with herpes zoster ophthalmicus (HZO) versus uncomplicated (nonophthalmic) herpes zoster (HZ), and to evaluate whether prior zoster vaccination modifies dementia risk in these groups.

Deidentified electronic health records from the TriNetX US Collaborative Network (71 health care organizations) were used to identify adults ≥50 years with incident HZ between January 01, 2005 and January 01, 2024.

In an overall matched analysis irrespective of vaccination status, HZO was associated with higher 3-year incident dementia risk compared with uncomplicated nonophthalmic zoster (2.45% vs. 1.88%; aHR 1.37, 95% CI 1.24-1.48). In vaccination-stratified matched analyses, dementia risk was also higher among patients with HZO compared with uncomplicated nonophthalmic zoster in both vaccinated stratum (2.30% vs. 1.78%; aHR 1.33, 95% CI 1.02-1.73) and unvaccinated stratum (2.67% vs. 2.34%; aHR 1.13, 95% CI 1.01-1.27). In separate within-phenotype matched analyses, prior zoster vaccination was associated with lower dementia risk among patients with HZO (2.48% vs. 2.89%; aHR 0.77, 95% CI 0.64-0.97) and among patients with uncomplicated nonophthalmic zoster (1.81% vs. 2.15%; aHR 0.75, 95% CI 0.69-0.80). Age-stratified analyses showed no significant difference in dementia risk for HZO versus uncomplicated nonophthalmic zoster in patients aged 50 to 69 years, but significantly elevated risk for HZO in those aged 70 to 79 years (1.66% vs. 1.09%; aHR 1.56, 95% CI 1.18-2.04) and 80 to 89 years (3.42% vs. 2.88%; aHR 1.21, 95% CI 1.04-1.41).

HZO is associated with a modest but significant increase in 3-year dementia risk compared with uncomplicated zoster, particularly among adults aged ≥70 years. Prior zoster vaccination is associated with substantially lower dementia risk in both HZO and uncomplicated zoster cohorts, supporting current shingles vaccination recommendations and suggesting potential cognitive benefits even when zoster is not fully prevented.