The predictor of interest was cumulative exposure to ACE inhibitors. Participants brought in all medications used in the prior two weeks and each was recorded by study staff. ACE inhibitors were classified into two groups according to their ability to cross the blood brain barrier. These determinations were made based primarily on experiments in rats. The two most common means of measuring ability to cross the blood brain barrier were 1) analysis of ground up, tissue specific ACE activity after administration of ACE inhibitors orally or subcutaneously and 2) tissue specific imaging of a radio-labeled ACE inhibitor after administration of various ACE inhibitors (which compete for binding with the radio-labeled ACE inhibitor).After review of the literature and pharmaceutical package inserts, captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril were classified as crossing the blood brain barrier, while benazepril, enalapril, moexapril, and quinapril were classified as not (Box). 20 (link)–28 (link) If data on use of ACE inhibitors were missing for an examination, and the values before and after that examination agreed, the missing value was replaced with the value observed for those visits. If data for more than two visits were missing, no imputations of missing data were attempted. Only 1.3% of the values were imputed.