Statin responder analysis for precision prevention of Alzheimer’s Disease

Abstract

AbstractBackgroundPreviously we identified reduced risk of Alzheimer’s Disease (AD) in statin users (Torrandell‐Haro et al. 2020). Identifying the subgroup of responders is an important step towards a precision statin therapy approach. This study aimed to investigate the effect of statin therapy on the incidence of Alzheimer’s Disease (AD) and other age‐related neurodegenerative diseases (NDD) by therapy, sex, and age group. Moreover, it sought to identify and describe responder vs non‐responder phenotypes to statin therapy based on demographic characteristics, comorbidity burden, and drug exposure.MethodA retrospective analysis was conducted using a US‐based insurance claims dataset of 53 million participants. Inclusion criteria included participants aged 45 years old or older, with no prior history of NDD before statin use, and with claims enrolled for at least 6 months prior and 3 years after start of statin therapy. A propensity score‐matched based on age, gender, region, comorbidities and cci was applied for group assignment. Records were surveyed for a diagnosis of AD 1 year after statin exposure. Sensitivity analyses for the detection of responders based on comorbidities and drug combinations were conducted.ResultOf the 1,293,952 participants who met inclusion criteria, 646,976 participants were exposed to statin therapy and were propensity score‐matched to 646,976 patients without exposure. Statin use was associated with a decreased risk of AD (RR [95% CI]: 0.54 [0.52–0.57]; P < .001) and other NDD. Additionally, men exhibited a greater risk reduction than women, which was driven by atorvastatin and simvastatin. Responders had a higher incidence of obesity and asthma whereas non‐responders were predominantly female and had an overall higher incidence of cardiovascular and cerebrovascular comorbidities.ConclusionStatin use was associated with a reduced risk of AD and other NDD, replicating previous results. Non‐responders were predominantly women with a high incidence of cardiovascular comorbidities. Characterization of responders to statin exposure advances a precision prevention approach, in which prescription guidelines consider neurological health and are adapted for at‐risk populations.This work was supported by the National Institute on Aging (grant R01AG057931), and the Women’s Alzheimer’s Movement and the Center for Innovation in Brain Science to Dr Brinton.