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Statins and Alzheimer Disease Risk

Friday, October 29, 2010 // Uncategorized

3/18/2009 10:27:52 PM

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People often worry about side effects of medications.  It’s a reasonable thing to do.  They worry about the effect on the liver which occurs early on and is not common.   statins are effective at reducing the risk of cardiovadcular disease.  Can they reduce the risk of other disease as well or is this some covert campaign by the pharmaceutical inductry to get us to prescribe more of them.  Don’t laugh.  there is a lot of money at stake. Some statins are soluble in water (hydrophilic) and others are soluble in fat (lipophilic).  I started taking a statin some years ago, not because my cholesterol was that high  (it had been creeping up in spite of diet and exercise, but my HDL was quite high), but because of the AFCAPS/TEXCAPS  study which was a primary prevention trial that showed that taking Mevacor (Lovastatin) reduced the risk of heart disease.  I don’t dread dropping dead of a heart attack, but the prospect of slowly losing my cognitive abilities was terrifying.  The part that interested me was that there was an approximately 30% risk reduction in the development of dementia.  I chose a lipophilic one because I thought that since the brain cells contain fat that one that penetrates fat may be more effective.  This study suggests that either category of statin may reduce the risk of alzheimer’s disease.Statins and Risk for Alzheimer Disease
In a large, prospective study, use of statin cholesterol-lowering drugs was associated with reduced risk for Alzheimer disease, independent of the drug’s lipophilicity.

These authors investigated the associations between statin and nonstatin cholesterol-lowering drugs and the development of Alzheimer disease (AD). They also distinguished between hydrophilic and lipophilic statins, as the latter have greater brain penetration.

For a mean of about 9 years, investigators followed 6992 nondemented individuals aged 55 or older at baseline who were participating in the Rotterdam Study, a prospective population study. The investigators obtained information about medication use from automated pharmacy services and performed comprehensive screening and follow-up cognitive evaluations. They compared the risk for AD in participants with any prior use of cholesterol-lowering drugs and those with no prior use, accounting for variations in demographics, vascular risk factors, duration of medication use, and presence of apolipoprotein E4 gene.

A total of 582 participants developed AD. Even after accounting for the potential confounders mentioned above, the use of statin cholesterol-lowering drugs (but not nonstatin cholesterol-lowering drugs) was associated with a lower AD risk compared with no cholesterol-lowering drug use (hazard ratio, 0.57). Moreover, both lipophilic and hydrophilic statins were associated with reduced risks for AD, with no significant difference between the two. The authors conclude that statins, but not nonstatin drugs, are associated with a reduced risk for AD, regardless of the statin’s lipophilicity.

Comment: This is the largest prospective study to date specifically designed to assess cognitive function in elders that addresses the relation between statin use and development of AD. The findings of this well-designed, comprehensive, and statistically rigorous study corroborate the results of most other epidemiologic studies in the field (e.g., JW Neurol Nov 4 2008). As an editorialist notes, two large studies in patients with cardiovascular disease did not show a significant reduction of dementia risk with statins, but the researchers did not adequately assess cognitive function. The editorialist also mentions two recent drug trials that did not show efficacy of commonly used statins in the treatment of mild-to-moderate AD. Therefore, statins might be more effective in preventing than in treating AD. A randomized clinical prevention trial could address this question, but such a trial would be difficult to design and complete, because follow-up might take many years to show any preventive benefits of the drug. Therefore, we will likely have to rely on the currently available data.

— Gad A. Marshall, MD

Dr. Marshall is Instructor in Neurology, Harvard Medical School, and Associate Neurologist, Memory Disorders Unit, Brigham and Women’s Hospital, Boston.

Published in Journal Watch Neurology March 17, 2009

Citation(s):
Haag MDM et al. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 2009 Jan; 80:13.

Original article (Subscription may be required)
Medline abstract (Free)

Sparks L. Statins and cognitive function. J Neurol Neurosurg Psychiatry 2009 Jan; 80:1.

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