Proposal to study antacids (PPIs and H2 blockers) and cognitive decline or
incident disease
 
   Lead Investigator:    Kyle Steenland
   Institution      :    Emory ADC
   E-Mail           :    nsteenl@emory.edu
   Proposal ID      :    682



   Proposal Description:
   Two recent reports of longitudinal data from Germany indicate that users  of proton pump inhibitors (PPIs), antacids used to treat heartburn, have an increased risk of dementia on the order of 40 (Gomm et al. 2016, Haenisch et al. 2015).  Kuller (2016) has discussed different mechanisms which might be involved, including increasing both production and degradation of amyloid (in animal models),  binding to tau, and lowering of B12-vitamin levels.  We seek to explore these findings in the NACC data base.  We plan to explore the association of baseline PPIs with incident MCI and dementia/AD, among those normal and those MCI at baseline, respectively.  We plan to use longitudinal (survival) analyses of progression to a worse diagnosis via Cox regression.  We also plan to analyze those always taking PPIs vs those never taking PPIs during follow-up We also plan to assess cognitive decline among users vs non-users of PPIs at baseline.  Again we will consider a group composed of those always taking PPIs vs those never taking PPIs during follow-up.  This analysis will use linear regression with mixed models to assess the interaction between a variable for follow-up time and use of PPIs our hypothesis is that those using PPIs will decline faster over time than those not using PPIs.  We will consider 10 cognitive tests from the UDS battery.  It will be important in both these analyses to control for covariates such as age/gender/race/education/smoking/obesity, and co-morbidities such as depression, diabetes, heart disease and hypertension.  We will also include a variable in the model for whether individuals are taking B12 vitamins and/or multivitamins.  We will exclude those with stroke from the analyses. We will follow methods used previously with NACC data (Steenland et al. 2012, Steenland et al. 2013, Goldstein et al . 2013, Wharton et al. 2015 ) Medication lists will be used to identify PPIs. Preliminary data indicate that about 12 of normals and MCI subjects in the NACC