Association of lipid-regulating drugs with dementia and related conditions: an observational study of data from the Clinical Practice Research Datalink

2BackgroundThere is some evidence that circulating blood lipids play a role in the development of Alzheimers disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of dementia and related conditions in the Clinical Practice Research Datalink (CPRD), an United Kingdom-based electronic health record database. MethodsA retrospective cohort study was performed using routinely collected CPRD data (January 1995 and March 2016). Multivariable Cox proportional hazard models, allowing for a time-varying treatment indicator, were used to estimate the association between seven lipid-regulating drug classes (vs. no drug) and five dementia outcomes (all-cause, vascular and other dementias, and probable and possible Alzheimers disease). ResultsWe analyzed 1,684,564 participants with a total follow-up of 10,835,685 patient-years (median: 5.9 years (IQR:2.7-9.7)). We found little evidence that lipid-regulating agents were associated with incidence of Alzheimers disease (probable HR:0.98, 95%CI:0.94-1.01; possible HR:0.97, 95%CI:0.93-1.01), but there was evidence of an increased risk of all-cause (HR:1.17, 95%CI:1.14-1.19), vascular (HR:1.81, 95%CI:1.73-1.89) and other dementias (HR:1.19, 95%CI:1.15-1.24). Evidence from a number of control outcomes indicated the presence of substantial residual confounding by indication (ischaemic heart disease HR: 1.62, 95%CI: 1.59-1.64; backpain HR: 1.04, 95%CI: 1.03-1.05; and Type 2 diabetes HR: 1.50, 95%CI: 1.48-1.51). ConclusionLipid-regulating agents were not associated with reduced Alzheimers disease risk. There was some evidence of an increased the risk of all-cause, vascular and other dementias, likely due to residual confounding by indication. 3 Key messagesO_LIA large cohort of patients from the Clinical Practice Research Datalink (CPRD) electronic health record database was assembled to examine the association of lipid-regulating agents, such as statins, with dementia outcomes. C_LIO_LIThere was little evidence that lipid-regulating agents were associated with Alzheimers disease, but there was some evidence for a harmful association with all-cause, vascular and other dementias. In all cases, the estimated associations were driven by the any statin subgroup, which comprised most participants in our cohort. C_LIO_LIEvidence from the control outcome analyses indicated strong residual confounding by indication, mostly likely related to vascular factors. C_LI