The use of statins may not be associated with lowering risk for Parkinson’s disease, according to a new study led by researchers at Penn State College of Medicine and National Institute of Environmental Health Sciences. The findings cast doubts on reports suggesting that the cholesterol-lowering medications may protect against this neurodegenerative brain disorder.
According to the National Parkinson Foundation, Parkinson’s disease affects about one million Americans and an estimated four to six million people worldwide. Although the cause of PD is unknown, damage to dopamine-producing neurons eventually leads to the movement disorders that are a hallmark of the disease.
Xuemei Huang, professor of neurology and vice chair for research, Penn State College of Medicine, previously reported an association between high blood cholesterol levels and lower incidence of PD. A low incidence of heart attack and stroke in PD patients in movement disorder clinics, despite their usually advanced age motivated these studies. Other studies also reported similar findings.
However, evidence has been somewhat inconsistent. The use of statins has also been associated with a lower incidence of PD in several recent epidemiology studies, leading some researchers to hypothesize that these medications, which lower levels of LDL - bad cholesterol - may protect against PD. Those studies, however, failed to account for cholesterol levels prior to the widespread use of statins in the U.S. population, Huang said, noting that as a strength of the new study.
The researchers looked at blood cholesterol levels, medications and PD status in participants in the ongoing, long-term Atherosclerosis Risk in Communities study. Cholesterol readings were taken at three-year intervals over the course of a decade from 1987 to 1989, before widespread statin use began.
“We confirmed our previous finding that high total cholesterol and LDL cholesterol were associated with a lower risk of PD,” Huang said. “Moreover, statin use over the course of the study did not protect against PD, and in fact appeared to increase PD risk in the long term. Although the analysis on statin use and PD was based on a fairly small number of PD cases, this preliminary data argues against the hypothesis that statins protect against PD.”
Statin Use May Reduce Parkinson’s Risk, Study Says
Millions of Americans take statins to lower their stroke and heart attack risks, but new research from Taiwan suggests the drug may offer another health benefit: cutting the odds of developing Parkinson’s disease.
Analyzing nearly 44,000 patients, scientists found that those who discontinued taking fat-soluble statins such as simvastatin (Zocor) or atorvastatin (Lipitor) were about 58 percent more likely to develop Parkinson’s than those who kept taking the drugs.
Fat-soluble statins are believed to cross the blood-brain barrier, unlike water-soluble statins such as rosuvastatin (Crestor) and pravastatin (Pravachol). The drugs may decrease inflammation and even modify dopamine pathways in the brain, which are linked to Parkinson’s, the study authors suggested.
“We are more glad than surprised to demonstrate the relationship,” said study author Dr. Jou-Wei Lin, a cardiologist at National Taiwan University Hospital. “Our analysis is observational . . . and further clinical trials targeting the association between statin use and Parkinson’s disease are still needed.”
The study is published online July 24 in the journal Neurology.
One in four Americans aged 45 and older takes a statin, according to Harvard Health. The drugs are used to lower cholesterol levels in the liver. In the United States, patients typically take the drugs for life once prescribed. In Taiwan, however, the national health insurance program has requested doctors stop prescribing statins when a patient’s cholesterol levels reach the treatment goal.
This Taiwanese policy, set to end on Aug. 1, allowed researchers to evaluate any potential difference in Parkinson’s risk in people who stopped statin use compared to those who continued taking the drug, Lin said. Parkinson’s disease is a progressive neurological condition resulting in movement problems such as stiffness, tremors and slurred speech.
Prior research examining the link between statin use and Parkinson’s disease showed inconsistent results. The new study, which took place from 2001 to 2008 on statin patients free of Parkinson’s disease, also showed that participants taking water-soluble statins developed Parkinson’s at about twice the rate as those taking fat-soluble statins.
Dr. Michael Okun, national medical director of the National Parkinson Foundation in Miami, said the findings were “intriguing but not surprising” in light of recent interest in lipid-lowering drugs to reduce Parkinson’s risk. But Okun said caution should be exercised in interpreting the study’s results.
The researchers reported their finding in the journal Movement Disorders.
Parkinson's risk" align="right" /> “One possibility,” Huang said, “is that statin use can be a marker of people who have High cholesterol which itself may be associated with lower PD risk. This could explain why some studies have found an association between use of these medications and low incidence of PD. Most importantly, this purported benefit may not be seen over time.”
Future research should focus on if and why cholesterol may protect against PD. Although blood cholesterol is not indicative of cholesterol in the brain, there is increasing evidence that PD may begin outside the brain. Statin-induced decreases in blood cholesterol levels may have unknown consequences in these peripheral areas. A compound called coenzyme Q10 that is produced alongside cholesterol may also be an area of future PD research. Statins reduce coenzyme Q10, which helps produce energy for cells and is hypothesized to have protective qualities in nerve cells.
“Statins have been proven to be effective in the primary and secondary prevention of cardiovascular events and stroke. Although some have proposed that statins might be a ‘cure-all’ drug,” Huang said, “this might be a case where what’s good for the heart isn’t good for the brain.”
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.
An estimated 43 million Americans currently take statins or are eligible for statin therapy. Recent updates to American Heart Association guidelines are expected to increase that number to 56 million or more. The new guidelines recommend statin use for some patients without High cholesterol but who have other risk factors for heart disease and stroke.
“Statins have been very important for preventing and treating vascular disease, but we need more research to understand if in some cases there is collateral damage,” Huang said.
Parkinson's risk" align="right" /> Until more epidemiological and basic research can be conducted to further parse out the associations between PD, cholesterol and statins, physicians and scientists should be cautious in promoting health benefits of statins for PD without a good understanding of clinical evidence and potential biological mechanisms, Huang advises.
Patients and physicians considering statins for cardiovascular health and stroke prevention should consider their individual cases.
“This is evidence that personalized medicine is better than a one-size-fits-all approach,” Huang said.
Other investigators on this project were Alvaro Alonso, M.D., Ph.D., University of Minnesota; Xuguang Guo, Ph.D., Westat Inc.; David M. Umbach, Ph.D., National Institute of Environmental Health Sciences; Maya L. Lichtenstein, M.D., Department of Neurology, Penn State; Christie M. Ballantyne, M.D., Baylor College of Medicine and Methodist DeBakey Heart Center; Richard B. Mailman, Ph.D., professor, Departments of Pharmacology and Neurology, Penn State; Thomas H. Mosley, Ph.D., University of Mississippi Medical Center; and Honglei Chen, M.D., Ph.D., National Institute of Environmental Health Sciences.
The Atherosclerosis Risk in Communities study is supported by the National Heart, Lung and Blood Institute and the National Institute of Environmental Health Sciences; and Huang receives National Institutes of Health funding.