Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea

Jooyun Kim, Hyeri Seok, Ji Hoon Jeon, Won Suk Choi, Gi Hyeon Seo, Dae Won Park

Scrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data. This population-based cohort study enrolled patients aged 60-89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer's disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity. During the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.15, p < 0.001). The Kaplan-Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer's disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13-1.18, p < 0.001). In conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer's disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.