Some blood pressure drugs may protect the brain

Blood pressure-lowering drugs called ACE inhibitors that penetrate the blood-brain barrier cut the risk of dementia, new research suggests.

Conversely, ACE inhibitors that do not get past the blood-brain barrier appear to increase the risk of dementia, relative to other blood pressure-lowering drugs.

The blood-brain-barrier refers to a protective mechanism that keeps many types of pathogens from entering the brain. Although this often prevents infectious agents from entering the brain, it keeps therapeutic agents from passing through as well.

Previous studies comparing the “neuroprotective” properties of different blood pressure medicines have yielded conflicting results, Dr. Kaycee M. Sink from Wake Forest University Medical Center in Winston-Salem, North Carolina, and her associates note.

To investigate further, they evaluated 1054 elderly men and women taking medication to control High Blood Pressure. All of them underwent brain imaging tests between 1991 and 1994. Subjects with evidence of dementia or heart failure were excluded.

According to a report in the latest issue of Archives of Internal Medicine, 414 study subjects were exposed to ACE inhibitors, including 224 who took only those drugs that cross the blood-brain barrier - namely, captopril, fosinopril, lisinopril, perindopril, ramipril, or trandolapril. Additionally, 138 subjects took only agents that do not cross the blood-brain barrier - namely, benazepril, enalapril, moexipril, or quinapril. Forty-five study subjects took both types of ACE inhibitors at different times, and the remainder took other blood pressure-lowering drugs.

During an average follow-up of 6 years, overall exposure to ACE inhibitors was not significantly different from other antihypertensives in reducing risk of dementia.

However, 3 years’ exposure to ACE inhibitors that do not cross the blood-brain barrier was associated with a 73% higher risk of the development of dementia and a 56% greater risk of disability in terms of being able to perform “activities of daily living” such as getting dressed and taking a shower.

By contrast, the use of ACE inhibitors that do cross the blood-brain barrier was associated with a 65% reduction in cognitive decline per year of exposure.

“Qualitatively,” Sink and associates write, “the direction of results for all outcomes favored ACE inhibitors that cross the blood-brain barrier.”

They call for a randomized controlled trial to confirm their findings.

SOURCE: Archives of Internal Medicine, July 13, 2009.