Simvastatin Linked to Reduced Incidence of Dementia, Parkinson's Disease

July 24, 2007 — Research links simvastatin to a reduction in the incidence of both dementia and Parkinson's disease (PD) of greater than 50%.
In contrast, atorvastatin is associated with a modest, but insignificant, reduction in the incidence of the 2 diseases, and lovastatin has no impact on incidence.
"This study suggests brain penetrant statins are more effective at preventing neurodegenerative disease than impenetrant statins," principal investigator Benjamin Wolozin, MD, from Boston University School of Medicine in Massachusetts, told Medscape.
"There are many statins out there. Some are very effective for preventing cardiovascular disease but not all of them cross the blood-brain barrier equally and, therefore, may not have the same impact on neurodegenerative disease.
"Simvastatin crosses into the brain very effectively, whereas atorvastatin just doesn't achieve as high a level [in the brain]. Lovastatin crosses the blood-brain barrier nicely but it is a first generation statin and therefore is just not as potent as some of the newer agents," he added.
The study is published in the July 19 issue of BMC Medicine.
Previous Research Yielded Conflicting Results
According to Dr. Wolozin, previous research looking at a potential protective effect of statins and dementia, including work by his group, has yielded conflicting results. In part, this was because the numbers of study subjects were not sufficiently powered to detect any statistically significant effect of statins on incident dementia.
However, the current study used the Decision Support System database of the US Veterans Affairs medical system. This large population-based database contains diagnostic, medication, and demographic information on 4.5 million subjects, 94.4% of whom are men.
Prescription utilization was tracked for every subject between 2003 and 2005. Lovastatin, simvastatin, and atorvastatin all had large numbers of prescriptions during this period. Data were obtained for 727,128 subjects taking simvastatin, 53,869 subjects taking atorvastatin, and 54,052 who were prescribed lovastatin.
Fluvastatin and pravastatin were also included. However, according to the authors, the number of subjects taking pravastatin was too small to produce reliable data. Furthermore, a marked increase in fluvastatin during the study period meant subjects' duration of exposure to this statin was much less than that for the other 3 agents. As a result, researchers did not pursue further studies of fluvastatin or pravastatin.
Magnitude of Effect Surprising
Using 3 models for analysis, researchers looked at the incidence of dementia and PD among subjects who had continuously used a statin for at least 7 months.
The first model adjusted only for age; the second model, for 3 major dementia risk factors, including cardiovascular disease, hypertension, and diabetes; and the third model, for the Charlson index, which is an index that provides a broad assessment of chronic disease.
With respect to dementia, researchers found simvastatin was associated with significant reduction in the incidence of dementia using any of the 3 models. In addition, said Dr. Wolozin, the study revealed a similar decrease in incident PD associated with simvastatin.
"We were very surprised by the size of the effect associated with simvastatin and that it worked for both Parkinson's disease and dementia. We were also surprised that atorvastatin hardly had any impact on the incidence of either disease," he said.
While a number of researchers have speculated that statins' apparent protective effect against dementia is caused by an amyloid-lowering mechanism, this study refutes that hypothesis.
"Dementia and Parkinson's disease are both neurodegenerative conditions. Dementia is typically characterized by the build-up of β-amyloid plaques, but this is not the case with Parkinson's. If you accept that statins are acting by a similar mechanism in both diseases it makes it very unlikely that it is acting through an amyloid-lowering mechanism. The most likely mechanism, and one that is most commonly accepted, is that statins protect the brain through an anti-inflammatory mechanism," he said.
Potential Mechanisms
On the other hand, he said a "provocative and interesting" animal study conducted by Johnson-Anuna and colleagues at the University of Minnesota and published in the February 2005 issue of the Journal of Pharmacology and Experimental Therapeutics suggests the neuroprotective effect of statins may be related to their ability to increase growth factors in the brain.
Based on the study's results, Dr. Wolozin said clinicians might want to consider an individual patient's family history when choosing a statin.
"If a patient has a family history of dementia, simvastatin may be a better choice than other agents. On the other hand, we know atorvastatin is somewhat better than simvastatin at preventing morbidity from cardiovascular disease, so if a patient has no dementia history but has cardiovascular risk factors, they may be better off taking atorvastatin. It really boils down to personalized medicine," said Dr. Wolozin.
He added that these findings need to be prospectively confirmed in other population-based studies.
BMC Med. Published online July 19, 2007.