Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.

ABSTRACT: We developed an endophenotype disease module-based methodology for Alzheimer's disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier. Based on retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio = 0.31, 95% confidence interval 0.25-0.39, P<1.0×10^-8). Propensity score stratified analyses confirmed that sildenafil is significantly associated with a decreased risk of AD across all four drug cohorts we tested (diltiazem, glimepiride, losartan and metformin) after adjusting age, sex, race, and disease comorbidities. We also found that sildenafil increases neurite growth and decreases

SUBMITTER: Fang J 

PROVIDER: S-EPMC9097949 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature