ACE and early-onset autosomal dominant Alzheimer disease: Agonism at the angiotensin type 4 receptor may improve spatial memory processing.15,16,45,55 However, it is important to recognize that unresolved complexity remains in understanding the interaction among antihypertensives, the renin angiotensin system, and cognitive outcomes.56 For example, data from human brain tissue of decedents show that domain-specific (C- and N-domain) changes in ACE1 in Alzheimer disease could promote angiotensin II–mediated disease progression.57 However, more evidence is needed on how different ACE inhibitors interact with the 2 ACE1 domains.