Second-Generation Antihistamines Not Linked to Higher Dementia Risk, Finds Study

The study cohort was carefully chosen to include individuals who are at least 50 years old and who have been diagnosed with either chronic urticaria, chronic sinusitis, or allergic rhinitis but not those who had a prior diagnosis of dementia at the beginning of the study period. The studied group was further stratified into two carefully chosen treatment groups, which consist of those taking either first-generation antihistamines (fgAH), second-generation antihistamines, or some other kind of appropriate alternatives that are not related to taking any antihistamines.

The controls consisted of nasal corticosteroids for individuals suffering from allergic rhinitis or chronic sinusitis, and short-term oral steroids for those having chronic urticaria. Propensity-score matching was used to account for selection bias among registry data by matching precisely based on 38 covariates, including demographics, socioeconomic variables, cardiovascular diseases, and healthcare use at the start of the study period.

Key findings:

• After stringent propensity matching, the statistical evaluation included a combined group of 48,238 chronic urticaria patients, 21,611 patients with chronic sinusitis, and 36,802 patients with allergic rhinitis, along with perfectly matched, equally sized control subjects.
• Hazard ratios computed across all comparative study groups showed that there were no increases in the risk of newly developed dementia among antihistamine users compared to controls without antihistamines during the course of the five-year observation period.
• Statistical analyses showed that there were no statistically relevant differences in the risk of developing long-term dementia between second-generation antihistamines versus first-generation users or steroid controls.
• In the subset of allergic rhinitis patients, the active use of intranasal corticosteroids was associated with a statistically lower risk of long-term dementia (p = 0.007).

To conclude, the overall results of this study do not show any higher risks of developing dementia related to the consumption of sgAHs. The low risk of dementia among patients with AR receiving corticosteroid treatment could be associated with its protective action, but not because of any negative influence of sgAHs on patients' health. These convincing results obtained during the TriNetX target trial emulation are a significant step toward preventive medicine.

Reference:

Olbrich, H., Kolkhir, P., Zuberbier, T., Ludwig, R. J., & Metz, M. (2026). Second-generation H1-antihistamines do not alter dementia risk in type 2 inflammatory diseases: A target trial emulation using real-world data. The Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2026.05.031