To establish efficacy of and molecular pathways for statins that have the potential to impact incidence of age-related neurodegenerative diseases. 

The pan-neurodegenerative risk profile among patients with statin exposure is unclear.

This retrospective cohort study surveyed U.S.-based Humana claims, which includes prescription and patient records from private-payer and Medicare insurance. Claims from 288,602 patients, aged 45 years and older without prior history of NDD or neurological surgery, were surveyed for a diagnosis of NDD starting 1 year following statin exposure. Patients were required to be enrolled with claims data for at least 6 months prior to first statin prescription and at least 3 years thereafter. Computational system biology analysis was conducted to determine unique target engagement for each statin.

Of the 288,602 participants included in the study, 144,214 patients (mean [SD] age, 67.22 [3.8] years) exposed to statin therapies, and 144,301 patients (65.97 [3.2] years) were not treated with statins. The mean (SD) follow-up time was 5.1 (2.3) years. All NDD incidence for all statins -except fluvastatin- was reduced with variances in individual risk profiles (3.60% vs 6.40%; RR, 0.56; 95%CI, 0.54-0.58; P <.001). To better understand the differences in the risk reduction efficacy profiles, a systems biology approach was conducted to identify protein/gene pathways associated with each statin. This analysis determined common vs unique biological mechanisms associated with each statin and enabled the identification of trends.