Association of probiotic medication use with incident Parkinson disease and alzheimer disease: a nationwide nested case-control study.

BACKGROUND

Growing evidence suggests that the intestinal environment may be involved in neurodegeneration, but evidence regarding routine probiotic medication use and subsequent neurodegenerative disease risk remains limited. We examined whether probiotic medication use was associated with the risk of incident neurodegenerative disease in a nationwide Japanese claims database.

METHODS

We conducted a nested case-control study using a Japanese health insurance claims database from January 2005 through April 2025. Adults aged 20-74 years with a first diagnosis of Parkinson disease or Alzheimer disease were identified as cases, and each case was matched with 3 controls by age, sex, and duration of insurance enrollment using incidence density sampling. Probiotic medication use was identified from outpatient prescription claims during a retrospective exposure window ending 2 years before the index month. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS

Among 20,322 cases (mean [SD] age, 51.7 [14.5] years; 10,595 [52.1%] males) and 60,966 matched controls, 6,485 cases (31.9%) and 23,235 controls (38.1%) had used probiotic medication. Overall, probiotic medication use was associated with a lower risk of incident neurodegenerative disease (Parkinson disease or Alzheimer disease) (OR, 0.56; 95% CI 0.54-0.58). In disease-specific analyses, the association remained directionally consistent for both Parkinson disease (OR, 0.54; 95% CI 0.52-0.57) and Alzheimer disease (OR, 0.63; 95% CI 0.58-0.68).

CONCLUSIONS

Probiotic medication use was associated with a lower risk of incident neurodegenerative disease. These findings support the potential relevance of the intestinal environment to neurodegeneration and warrant further investigation in prospective studies better suited to causal inference.