Statins May Curb Parkinson's Disease Risk

Megan Brooks

March 13, 2012

March 13, 2012 — Regular use of cholesterol-lowering statins may help reduce the risk for Parkinson's disease (PD), particularly in adults younger than age 60 years, according to new data from the ongoing Harvard School of Public Health Health Professionals Follow-Up Study and the Nurses' Health Study.

The data suggest that long-term use of statins "could provide a benefit against risk of developing PD," Xiang Gao, MD, PhD, from Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, who led the study, told Medscape Medical News. "However, our findings are preliminary and need to be interpreted with caution."

Dr. Xiang Gao

For example, only about 70% of those receiving cholesterol-lowering drugs in this study were actual statin users, the researchers note. The analysis yielded only marginally significant results in favor of statins' neuroprotective effects and "could be due to chance," the investigators say.

The study is published in the March issue of Archives of Neurology.

26% Risk Reduction Overall

The analysis included 38,192 men from Health Professionals Follow-Up Study and 90,874 women from the Nurses' Health Study. Information on regular cholesterol-lowering drug use, a surrogate marker of statin use, was collected via questionnaire in 1994. During 12 years of follow-up (1994 to 2006), the researchers documented 644 incident cases of PD: 338 in women and 306 in men.

The researchers report that the incidence of PD was lower among statin users relative to nonusers. The pooled relative risk (RR) of PD was 0.74 (95% confidence interval [CI] 0.54 - 1.00; P = .049) comparing current statin users with nonusers, after adjusting for several potentially confounding factors including age, smoking, caffeine intake, and the use of ibuprofen, which has been consistently found to be inversely associated with PD risk (pooled RR, 0.62), the researchers note.

There was a significant interaction between statin use and age in relation to PD risk (P for interaction = .03). A significant protective effect was apparent in subjects younger than 60 years at the beginning of follow-up but not among those who were older (Table).

Table. Reduction in Risk of Parkinson’s Disease with Statin Use By Age Group

Group Adjusted Pooled Relative Risk 95% Confidence Interval P
< 60 years 0.31 0.11 - 0.86 .02
> 60 years 0.83 0.60 - 1.14 .25

Protective Effect Plausible; Results Mixed

Recently, statins have been shown to possess potent anti-inflammatory and immune-modulating effects, which fueled the hypothesis that statins could be neuroprotective agents, Dr. Gao and colleagues note in their report. Yet, prospective and epidemiologic studies to date have generated mixed results regarding statin use and PD risk, and the overall evidence for benefit "remains unconvincing," they say.

The researchers caution that their analysis has several limitations. Chief among them is the fact that they classified use of any cholesterol-lowering drugs before 2000 as statin use; as a result, misclassification was "inevitably introduced," they say. However, based on US retail prescription data, statins accounted for 72% of total cholesterol-lowering drug use in 1994, 80% in 1996, and more than 90% in 2000.

The lack of information on which specific statin drugs were used is another limitation. "We would like to test the effects of each specific statin as their ability to enter the brain varies and so they may have different effects on PD," Dr. Gao commented.

For example, lovastatin and simvastatin have been shown to have more potency to cross the blood-brain barrier relative to atorvastatin calcium. The researchers say it is likely that their results are driven by these 2 statins given that they were the most commonly prescribed in the mid-1990s.

The authors say they cannot exclude residual confounding because of the observational nature of the study.

Clearly more study is warranted, the researchers conclude, not only because statins may have neuroprotective effects, but also because they may have unfavorable effects by lowering the level of plasma coenzyme Q10, which may itself be neuroprotective in PD.

The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Gao has been a consultant for Teva Pharmaceuticals.

Arch Neurol. 2012;69:380-384. Abstract

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