Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression

Abstract

There is evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes.1,2⇓ Angiotensin-converting enzyme (ACE) is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of patients with Alzheimer disease (AD).1 In an animal model with AD, brain-distributing ACE inhibitors are reported to rescue neuronal damage and improve behavior.2 Furthermore, we have shown that brain-penetrating ACE inhibitors can reduce the incidence of AD in elderly hypertensive patients.3 In the present study, we tested the hypothesis that treatment with brain-penetrating ACE inhibitors3 would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension. We performed a randomized, prospective, parallel group trial with 1-year exposure to study medications. Participants were recruited from three long-term care facilities in Sendai, Japan. Patients eligible for this study had a diagnosis of mild to moderate AD,4,5⇓ were aged 65 years and older, had Mini-Mental State Examination (MMSE) scores within the range of 13 to 23, showed no evidence of stroke; insulin-dependent diabetes mellitus, or other endocrine disorders, or asthma or obstructive pulmonary disease, and had a blood pressure of higher than 140 mm Hg systolic or 90 mm Hg diastolic. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria with no clinical or laboratory evidence of a cause other than AD for dementia.5 Brain MRI was obtained in all participants within 3 months prior to the study enrollment to exclude patients with possible or probable vascular dementia and other neurodegenerative dementias. Patients …