OBJECTIVES: Numerous studies have reported the protective effect of renin-angiotensin system (RAS) inhibitors on neurodegenerative diseases. Some studies have also reported that the blood-brain barrier (BBB) permeability of RAS inhibitors could be linked to greater neuroprotection and a lower risk of Alzheimer’s disease (AD). This study aimed to assess the effects of different types of RAS inhibitors on the risk of incidence of AD.

METHODS: We conducted a population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. Patients aged 60 years or older, who had been diagnosed with ischemic heart disease between January 1, 2009, and June 31, 2009, were recruited. The association between the use of RAS inhibitors and incident AD was evaluated using a multivariate Cox proportional hazard regression model by adjusting age, sex, type of insurance, comorbid diseases, and concurrent medications.

RESULTS: A total of 82,456 subjects identified, 9,682 individuals were classified as new users of RAS inhibitors and 72,774 did not use any RAS inhibitors. After propensity score matching, 9,682 participants in both RAS and non-RAS groups were included in the analyses. The results showed that the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) was not statistically associated with a reduced risk of AD. However, individuals who received BBB-crossing RAS inhibitors had a lower risk of AD (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.83–0.98), compared to non-RAS users. Further analyses demonstrated that BBB-crossing ARBs significantly reduced the risk of incident AD (aHR, 0.81; 95% CI, 0.73–0.90).

CONCLUSIONS: The risk of occurrence of AD was prevented by the use of BBB-crossing ARBs, but not by other types of RAS inhibitors.