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ACE Inhibitors May Slow Cognitive Decline
Centrally acting angiotensin-converting enzyme inhibitors (CACE-Is) reduce the rate of cognitive decline in patients with dementia, regardless of blood pressure levels at the time of their hypertension diagnosis, a new study has found.
The study also shows that the rate of cognitive change was improved in the first 6 months after dementia patients started taking these drugs.
“There’s a growing body of literature now showing that these drugs slow down the deterioration that people with Alzheimer’s disease experience, probably by between 20% and 30% a year compared to another antihypertensive drug or no centrally acting ACE inhibitor,” said study author D. William Molloy, professor, Center for Gerontology and Rehabilitation, University College Cork, Cork City, Ireland.
The results prompt the question of whether these CACE agents would actually delay or prevent the onset of Alzheimer’s disease (AD) in people with normal blood pressure who are at risk for dementia, said Dr. Molloy.
The study was published online July 22 in BMJ Open.
Newly treated patients also showed improvements. The median decline in scores for the NewACE-I group on the SMMSE was -1.2 points during the first 6 months of taking the drug.
Unlike some studies that show significant change but aren’t clinically significant, this study uncovered a more definitive effect from use of CACE-I drugs, said Dr. Molloy. “This was clearly clinically significant, I think; it’s not just Mickey Mouse change; it’s significant change.”
Among the different CACE-I agents, perindopril appeared to outperform the others, according to Dr. Molloy. “From the data we looked at, my impression was that perindopril was better than ramipril. It has a longer half-life so it has a smoother action over 24 hours, and it might have better tissue penetration.”
It didn’t seem to matter how long patients had been taking a CACE-I. Researchers didn’t have enough data on dosage to determine whether this affected the rate of cognitive decline, said Dr. Molloy.
What’s clear from this study is that CACE-I drugs, which are lipid soluble, do not work by lowering blood pressure, said Dr. Molloy. “We show here that in the ACE inhibitor class, it’s the ones that cross the blood-brain barrier that are having the effect, suggesting that it’s not a blood pressure–lowering effect, that there’s something about this penetration of the central nervous system.”
Anti-inflammatory Effect
But it’s not clear how CACE drugs actually slow down cognitive decline in patients with AD. Dr. Molloy believes, though, that AD is probably the result of chronic inflammation in the brain and that CACEs have an effect on that inflammation.
By crossing over, they may penetrate the tissues and they may be having some kind of anti-inflammatory effect or somehow switch off the inflammation.
In addition to ACE inhibitors, other antihypertensive drugs have been associated with a lower risk of developing dementia, including calcium channel blockers, diuretics, and angiotensin-receptor blockers.
BMJ Open. Published online July 22, 2013.
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