Abstract
BACKGROUND: Evidence suggests that some infectious diseases, such as herpes zoster (HZ), are associated with elevated risk of subsequent dementia, while certain anti-viral medications are associated with lower risk. We sought to evaluate associations between HZ diagnosis and treatment with incident dementia in a large, retrospective matched cohort. METHODS: Using ICD-9 and ICD-10 diagnosis codes in electronic medical records, we identified members of Kaiser Permanente Northwest age 50 and older from 2000-2019 with a HZ diagnosis during this period. A comparison group without HZ diagnosis was individually matched 3:1 on age at HZ diagnosis date (index date), sex, and membership length prior to index date. We excluded subjects with dementia diagnosed before the index date. Antiherpetic medication was identified using pharmacy fills 1 month before to 12 months after the index date. We employed survival analysis to examine the associations between dementia and HZ diagnosis and antiherpetic medication, adjusting multivariable models for demographic and clinical factors. We stratified on age and sex and conducted a sensitivity analysis with a 5-year lag period. RESULT: The study included 101,328 persons, 25,332 with HZ. Over a median follow-up of 4.8 years, 6,000 developed dementia. HZ diagnosis was not associated with higher hazard of dementia (hazard ratio (HR) = 0.99, 95% CI 0.93-1.05) in the primary analysis. Among persons with HZ diagnoses, the HR for receipt of any antiherpetic medication was 0.79 (95% CI 0.70-0.90) in univariate analysis and 0.88 (95% CI 0.77-1.00) after adjustment for demographic and clinical factors. Dementia was not associated with trends in duration of medication use or cumulative dose. CONCLUSIONS: We found little evidence for an association between HZ diagnosis and dementia overall. Antiherpetic medication prescribed around the time of HZ diagnosis was statistically associated with lower risk of subsequent dementia in some but not all analyses and subgroups.