Brain-penetrating ACE inhibitors slow Alzheimer's

Drugs usually used to treat high blood pressure and heart failure may also be helpful for Alzheimer's patients, Japanese researchers report.

Certain angiotensin-converting enzyme (ACE) inhibitors such as captopril and perindopril (brand-name Aceon), which are able to cross the blood-brain barrier, appear to slow the progression of Alzheimer's disease, according to a report in the medical journal Neurology.

"Use of brain-penetrating ACE inhibitors might provide clinical benefits for the treatment of Alzheimer's disease patients with hypertension," Dr. Takashi Ohrui from Tohoku University School of Medicine, told Reuters Health.

Ohrui and colleagues compared mental status scores for 162 Alzheimer's patients before and after treatment with a brain-penetrating or non-brain-penetrating ACE inhibitor or a calcium-channel blocker.

After 1 year of treatment, the deterioration in mental performance was lowest in the group treated with brain-penetrating ACE inhibitors captopril or perindopril, the authors report, averaging a decline of 0.6 points.

The declines in mental status scores were considerably larger (4.6 points) in patients treated with non-brain-penetrating ACE inhibitors enalapril (e.g., Vasotec, Lexxel) or imidapril (Tanatril), and in those treated with calcium-channel blockers (average decline, 4.9 points).

"These results suggest that brain-penetrating ACE inhibitors might have a clinical benefit even in patients with limited activities of daily living," the authors conclude.

"This study's findings are provocative and exciting," writes Dr. David S. Knopman from the Mayo Clinic in Rochester, Minnesota, in a related commentary, "but readers must be skeptical."

He cites a number of weaknesses in the study, and says the findings "must be replicated in carefully controlled, randomized, blinded studies."

Ohrui added, "We plan to do experimental research using an animal model to study the effectiveness of brain-penetrating ACE inhibitors in Alzheimer's disease."

SOURCE: Neurology, October 2004.