Time until incident dementia among Medicare beneficiaries using centrally acting or non‐centrally acting ACE inhibitors

BACKGROUND: Centrally active (CA) angiotensin-converting enzyme inhibitors (ACEIs) are able to cross the blood–brain barrier. Small observational studies and mouse models suggest that use of CA versus non-CA ACEIs is associated with a reduced incidence of Alzheimer's disease and related dementias (ADRD). OBJECTIVE: The aim of this research was to assess the effect of CA versus non-CA ACEI use on incident ADRD. DESIGN: This is a retrospective cohort study with a non-equivalent control group. SETTING AND PATIENTS" This study used a national random sample of Medicare beneficiaries enrolled in Part D with an ACEI prescription. A prevalent ACEI user cohort included beneficiaries (n = 107 179) with an ACEI prescription prior to 30 April 2007; beneficiaries without an ACEI prescription before this date were defined as incident ACEI users (n = 9840). MEASUREMENTS: The main outcome was time until first diagnosis of ADRD in Medicare claims. RESULTS: The unadjusted, propensity-matched and instrumental variable analyses of both the prevalent and incident ACEI user cohorts consistently showed similar time until incident ADRD in those taking CA ACEIs compared with those who took non-CA ACEIs. LIMITATIONS: The limitations of this study include the use of observational data, relatively short follow-up time and claims-based measure of cognitive decline. CONCLUSIONS: In this analysis of Medicare beneficiaries who were prevalent or incident users of ACEIs in 2007–2009, the use of CA ACEIs was unrelated to cognitive decline within 3 years of index prescription. Continued follow-up of these patients and more sensitive measures of cognitive decline are necessary to determine whether a cognitive benefit of CA ACEIs is realized in the long term.