Acetylcholinesterase inhibitors considerably affect the salivary microbiome in patients with Alzheimer's disease.

Microbiome alterations are reportedly linked to systemic disease progression and medication. However, the effects of central nervous system drugs on the microbiome of patients with neurodegenerative diseases, such as Alzheimer's or Parkinson's disease, are poorly understood. Here, we comprehensively analyzed the effects of medication on the salivary and gut microbiomes of patients with Alzheimer's or Parkinson's disease. Comparative analyses of the effects of disease severity and drug use revealed that anti-dementia (DE) drugs, particularly acetylcholinesterase inhibitors, had a greater effect on compositional changes in the salivary microbiome than on those in the gut microbiome. Multivariate analyses incorporating anti-DE drug use showed that microbial signatures may serve as promising disease biomarkers, enabling the development of more precise predictors of cognitive function. Our findings will facilitate the advancement of diagnostic tools leveraging the salivary microbiome.