Atovaquone/Proguanil and Zoster Vaccines Reduce Alzheimer’s Risk: A Role for Toxoplasma gondii?
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INTRODUCTION
Identifying modifiable risk factors for Alzheimer’s disease (AD) may provide insights into its etiology and inform prevention strategies.
METHODS
We analyzed 9,124 AD patients and 18,248 matched controls from a national cohort (2004– 2024). Logistic regression, adjusted for age, gender, socioeconomic status, and comorbidities, identified medications tied to significant AD risk reduction (OR<0.5, FDR<0.05) for the decade following their uptake. Findings were validated in TriNetX (120M U.S. patients) using propensity score-matched Cox models for dementia hazard ratios (HR).
RESULTS
Atovaquone/proguanil (Ato/Pro) use was associated with lower AD risk (OR 0.36 [95% CI, 0.20– 0.61]; HR 0.43 [95% CI, 0.35–0.53]), as were both varicella-zoster virus (VZV) vaccines (OR 0.16–0.37). Toxoplasma gondii seropositivity increased AD risk (HR 2.43, p=0.001).
DISCUSSION
Ato/Pro and VZV vaccines were AD-protective, with Ato/Pro’s effect strongest in VZV-unvaccinated patients, supporting a hypothesis that latent T. gondii infection, reactivated by herpesvirus superinfection, may drive AD pathogenesis.
