Angiotensin-converting enzyme inhibitors (ACE inhibitors) that cross the blood-brain barrier may slow the rate of cognitive decline associated with Alzheimer’s disease, according to an article in the October 12th issue of Neurology.

The Japanese study involved 162 people living in long-term care facilities who had mild to moderate Alzheimer’s disease and hypertension. Participants were divided into three groups for one year based on type of antihypertensive medication: a brain-penetrating ACE inhibitor, a non-brain-penetrating ACE inhibitor, or a calcium channel blocker. The two brain-penetrating ACE inhibitors used were perindopril or captopril.

The participants’ thinking and memory skills were tested at the beginning of the study and again at the end. The cognitive skills of those who took the brain-penetrating ACE inhibitors declined only slightly over the year. In contrast, the skills of those who took the other drugs declined significantly.

At the beginning of the study, participants had an average score of about 20 on the exam. The scores of those on brain-penetrating ACE inhibitors declined by an average of 0.6 points. The scores of those on non-brain-penetrating ACE inhibitors declined by an average of 4.6 points. The average decline was 4.9 points for those on calcium channel blockers.

“These brain-penetrating ACE inhibitors might have benefits not only for the prevention but also for the treatment of mild to moderate Alzheimer’s,” said study author Takashi Ohrui, MD, of Tohoku University School of Medicine in Sendai, Japan.

“These findings are provocative and exciting, but the results must be replicated in carefully controlled, randomized, blinded studies,” said neurologist David Knopman, MD, who wrote a commentary on the study.

Knopman noted that the study has several limitations. The participants knew which drug they received, and the researchers were not blinded to which participants received which drug. Another weakness is that there is no way to tell whether one of the brain-penetrating ACE inhibitors was more effective than the other in slowing the effects of Alzheimer’s disease, Knopman added.

The researchers do not know how the brain-penetrating ACE inhibitors acted to slow the cognitive decline seen in the patients. The brain-penetrating ACE inhibitors did not lower blood pressure more than the other drugs in the study. Researchers have found more angiotensin-converting enzyme (ACE) in the brains of people with Alzheimer’s disease than people who don’t have the disease. The brain’s renin-angiotensin system controls blood pressure and may play an important role in learning and memory processes.

“The ACE inhibitors may work directly on the renin-angiotensin system in the brain,” Ohrui said.