Statins protective against Parkinson's: More evidence

Taipei, Taiwan - Further evidence that statin use is associated with a reduction in risk of Parkinson's disease has come from a population study conducted in Taiwan [1].

The study, published online July 24, 2013 in Neurology, was led by Dr Yen-Chieh Lee (Cathay General Hospital, Taipei, Taiwan).

In a large population of statin users, researchers found a lower risk of Parkinson's in those who continued taking lipophilic statins compared with those who discontinued, having reached their cholesterol goal.

Authors of an accompanying editorial conclude: "For those who have to be on statins, it is a comforting thought that there is a potential added advantage of having a lower risk of Parkinson's disease and possibly other neurologic disorders as well" [2].

More basic science needed

Commenting on the study, Dr James Beck (Parkinson's Disease Foundation, New York, NY) said: "For the one million people with Parkinson's disease in the US who need better treatments now, this is good news. However, we must remember that without a solid footing of how statins and similar drugs work, widespread testing or use of these drugs are like an expensive house built upon sand: it will be of little scientific benefit if it meets failure. We need scientists conducting the basic science to understand the drugs, if they are to be of benefit over the long term."

In the Neurology paper, Lee et al explain that a possible protective role for statins has been suggested because of their potent anti-inflammatory effects, and in animal models, they have been shown to reduce intraneuronal alpha-synuclein aggregations, a protein associated with Parkinson's. Some previous studies have reported a link between statins and reduced incidence of Parkinson's disease, but most of these have relied on self-report questionnaires to gather information on statin use, and some studies failed to control for important confounders, such as diabetes and use of certain drugs often used by patients taking statins that have been shown to affect the risk of Parkinson's.

In the current study, Lee and colleagues took advantage of Taiwan's compulsory national health insurance program, which allowed capture of comprehensive data on use of statins and other drugs. Dispensing records were available for validation. The development of Parkinson's disease was identified using hospital diagnosis codes.

A total of 43 810 patients who were taking statins but did not have a Parkinson's diagnosis were recruited between 2001 and 2008. Because Taiwan's reimbursement policy requests statin discontinuation once LDL-cholesterol falls below 100 mg/dL, researchers could evaluate the effect of discontinuing statins on risk of Parkinson's.

Given that the lipophilicity of statins affects their penetration through the blood-brain barrier, researchers focused on differences in Parkinson's incidence between patients taking lipophilic and hydrophilic statins.

Hydrophilic/lipophilic differences

Results showed that the incidence rate for Parkinson's in patients taking lipophilic or hydrophilic statins was 1.68 vs 3.52 per one million person-days, respectively.

Continuation of lipophilic statins was associated with a decreased risk of Parkinson's compared with statin discontinuation, and this association was not modified by comorbidities or medications. There was no association between hydrophilic statins and incidence of Parkinson's.

Parkinson's risk on continuing vs discontinuing statin therapy

Among lipophilic statins, a significant effect was observed for both simvastatin (HR 0.23) and atorvastatin (HR 0.33). Lovastatin and fluvastatin also showed a trend toward reduced risk of Parkinson's. The effect was stronger in women than in men and was obvious at all age groups.

However, researchers found no effect of long-term statin use or cumulative dose on the incidence of Parkinson's.

Is it statins or cholesterol?

The researchers acknowledge that there may be an effect of cholesterol levels or mortality rates on their results, with the possibility that patients who continued on statins would have had higher levels of LDL-cholesterol than those who discontinued and hence may have had a higher mortality rate that resulted in a lower incidence of Parkinson's. However, on examination of mortality rates, they found that patients who continued on statins actually had a lower chance of dying compared with those who discontinued use.

Unfortunately, data on cholesterol levels were not available, and the authors note that further longitudinal studies, including measures of cholesterol levels over time, are needed to clarify the interrelated roles of LDL-cholesterol, statin use, and Parkinson's disease.

In an accompanying editorial, Drs Eng-King Tan and Louis CS Tan (Duke NUS Graduate Medical School, Singapore) note that the use of a compulsory national health insurance program to access comprehensive data on statin use was a key strength of the study, and the observed differential effect between lipophilic and hydrophilic statins provides additional insights into the possible underlying pathophysiologic mechanism of the potential protective effect.

However, they also point out that there was a lack of information about cigarette smoking and caffeine intake and that it is not clear whether the study was sufficiently powered to detect the differential effect between hydrophilic or lipophilic statins based on the amount of exposure.

"While there is some consensus that lipophilic statins can easily cross the blood-brain barrier and are likely to have a direct neuroprotective effect, the possibility of an indirect effect through changes in cholesterol or other lipids cannot be discounted," they write. They add that, as actual levels of cholesterol and lipids were not available, it is possible that those who continued taking statins had much higher cholesterol levels, which could affect Parkinson's risk.

The editorialists report that there is mounting evidence supporting an effect of statins on pathophysiologic processes linked with Parkinson's, such as mitochondrial function, oxidative stress, and protein accumulation. "While there is a biological basis for the association between statin use and Parkinson's disease, more research is required to further decipher the specific pathways or targets that are involved in statin-induced neuroprotection," they state.

Source: www.theheart.org