Statins Protective Against Parkinson's: More Evidence

July 26, 2013

Further evidence that statin use is associated with a reduction in risk for Parkinson's disease has come from a population study from Taiwan.

The study, published online in Neurology on July 24, was conducted by a team led by Yen-Chieh Lee, MD, Cathay General Hospital, Taipei, Taiwan.

In a large population of statin users, they found a lower risk for Parkinson's in those who continued taking lipophilic statins compared with those who discontinued statins upon 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 PD [Parkinson's disease], and possibly other neurologic disorders as well."

More Basic Science Needed

Commenting on the study, James Beck, PhD, vice president of scientific affairs at the US Parkinson's Disease Foundation, said, "For the 1 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." Dr. Beck was not involved in the study.

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

For the current study, the researchers 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 by 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 the discontinuation of statin therapy once low-density lipoprotein (LDL) cholesterol levels fall below 100 mg/dL, the researchers evaluated the effect of discontinuing statins on risk for Parkinson's.

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

Hydrophilic/Lipophilic Differences

Results showed the incidence rate for Parkinson's was 1.68 per 1 million person-days for patients taking lipophilic statins and 3.52 per 1 million person-days for those taking hydrophilic statins.

Continuation of lipophilic statins was associated with a decreased risk for Parkinson's as compared with statin discontinuation, and this association was not modified by comorbid conditions or medications. But there was no association between hydrophilic statins and incidence of Parkinson's.

Table. Parkinson's Risk on Continuing versus Discontinuing Statin Therapy

Endpoint Lipophilic Statins Hazard Ratio (95% Confidence Interval) Hydrophilic Statins Hazard Ratio (95% Confidence Interval)
Main analysis 0.42 (0.27 - 0.64) 0.95 (0.55 - 1.65)
Multivariable analysis (adjusted for multiple confounders) 0.44 (0.29 - 0.66) 0.91 (0.53 - 1.58)


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

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

Is It Statins or Cholesterol?

The researchers acknowledge that cholesterol levels or mortality rates may have affected their results, with the possibility that patients who continued to receive statins would have had higher levels of LDL cholesterol than those who discontinued and hence may have had a higher mortality that resulted in a lower incidence of Parkinson's. But on examination of mortality rates in the 2 patient groups, they found that patients who continued to receive statins actually had a lowered chance of dying than those who discontinued the drugs.

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

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

But they also point out that there was a lack of information 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 with statins had much higher cholesterol levels and this could have an effect on Parkinson's risk.

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

The study was supported by the Taiwan Ministry of Education. The authors have disclosed no relevant financial relationships.

Neurology. 2013;81:1-7. Published online July 24, 2013. Abstract   Editorial


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