NEW YORK (Reuters Health) - Findings from the Cardiovascular Health Study-Cognition Substudy suggest that angiotensin-converting enzyme (ACE) inhibitors that cross the blood-brain barrier reduce the risk of incident dementia. Conversely, non-centrally active ACE inhibitors appear to increase the risk, relative to other antihypertensive drugs, investigators report in the Archives of Internal Medicine for July 13.
According to lead author Dr. Kaycee M. Sink from Wake Forest University Medical Center in Winston-Salem, North Carolina, and her associates, previous research comparing neuroprotective properties of different antihypertensives has yielded conflicting results.
In a prospective, population-based study, Dr. Sink’s group evaluated the incidence of cognitive decline, dementia and incident disability based on performance of activities of daily living in 1054 subjects (mean age 75 years; 64% female; 76% white) who underwent brain MRI between 1991 and 1994. All of the subjects were taking medication to control hypertension. Those with prevalent dementia or congestive heart failure were excluded.
The authors report that 414 subjects were exposed to ACE inhibitors, including 224 who took only centrally active agents (captopril, fosinopril, lisinopril, perindopril, ramipril, or trandolapril);138 took only noncentrally active agents (benazepril, enalapril, moexipril, or quinapril), 45 who took both at different times, and the remainder took other antihypertensive drugs.
During a mean 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 incident dementia and a 56% greater risk of disability in terms of incident instrumental activities of daily living.
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, according to Modified Mini-Mental State Examination scores, “a global measure of cognition.”
“Qualitatively,” Dr. 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 of a centrally active ACE inhibitor to confirm their findings.
References:
Arch Intern Med 2009;169:1195-1202.
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