Low LDL, Statin Use, and Parkinson's Disease Point to Possible Paradox

Shelley Wood

January 18, 2007

January 18, 2007 (Chapel Hill, NC) - Researchers in North Carolina say that a link they found between low LDL-cholesterol concentrations and Parkinson's disease
(PD), coupled with signs that PD incidence is lower in people taking statins, may have important implications for PD etiology and public health [1].

The observations further complicate the PD/CVD paradox, lead author on the study Dr Xuemei Huang (University of North Carolina, Chapel Hill) explained to heart wire : risk factors for CVD, such as smoking, have been linked to reduced PD, while incidence of MI and stroke is reduced in PD patients.

"The peak age for developing Parkinson's is between 50 and 70 years of age, yet these patients have remarkable cardiovascular health, even though this is also a peak time for stroke and heart attack," Huang said. "I did a search on this topic and found some studies in the literature to support my hunch that yes, Parkinson's patients do seem to have lower prevalence of heart disease and stroke."

By contrast, there is almost no published data linking LDL levels, statins, and PD, Huang said.

Making waves in the mainstream press

Results of the study appeared online December 18, 2006 in Movement Disorders, but the story has since made waves in the mainstream press, with several stories suggesting that ever-increasing statin use could lead to more Parkinson's disease.

But speaking with heart wire , Huang was insistent that their retrospective study is one of the first studies to examine the link between LDL-C and Parkinson's disease and is primarily hypothesis generating. "This study was retrospective in nature, and we could not make a casual inference between LDL-C and/or statin use and risk of PD," the authors write.

Huang et al obtained fasting lipid profiles from 124 patients with PD recruited from a hospital-affiliated movement disorder clinic and 112 controls, made up of spouses of the PD patients. The authors found that after adjustment for age, gender, smoking status, and use of cholesterol-lowering medications, low LDL was associated with a higher occurrence of PD. Compared with people with the highest LDL (>139 mg/dL), patients with the lowest LDL (<92) were more than twice as likely to have Parkinson's disease. Equally intriguing, however, they found that the use of statins was related to lower PD occurrence.

"The main finding is that people with lower LDL cholesterol, which is usually a good thing, have an increased prevalence of PD, which adds another paradox to the Parkinson's/heart-disease relationship," Huang said. "We also found that Parkinson's patients, compared with people who don't have PD, are less likely to use statins, and this was a pretty significant finding."

There are two ways to interpret this secondary finding, Huang said. "Number one, it's possible that PD patients have lower LDL all their lives, so they are less likely to see a doctor for high cholesterol and require a statin."

The second hypothesis relates to other recent findings suggesting that statins may be neuroprotective, as seen in studies of dementia, Alzheimer's, and multiple sclerosis. "Our data tend to support the idea that Parkinson's patients, because they have a lower cholesterol to start with, are less likely to be put on statins and so couldn't benefit from the statin's neuroprotective effect," Huang explained. "Statins may be helpful in protecting against Parkinson's, or by lowering cholesterol, they may contribute causally to Parkinson's disease. So two very opposite scenarios that could have a huge public-health impact. . . . Either way, it's very interesting and deserving of further study."

Statin-Parkinson'slink makes sense

Commenting on the study for heart wire , Dr Benjamin Wolozin (Boston University, MA) called the data "reasonably robust" but cautioned, "The study is small and the confidence intervals are wide, which is oftentimes an indication that the study's findings are relatively weak and need to be replicated."

Wolozin rejects the suggestion that higher statin use, by lowering LDL, could lead to increased Parkinson's disease. More plausibly, he suggests, the Parkinson's disease process itself may affect cholesterol levels, rather than the reverse. In Alzheimer's disease, for example, mid-life cholesterol levels may be more telling than cholesterol levels once Alzheimer's is diagnosed, he said. "There's actually not a strong correlation between cholesterol and Alzheimer's disease late in life. It seems that, early in the disease process, probably 15 years before people develop AD, their cholesterol starts to go down." Extrapolating to PD, says Wolozin, "you could argue either that people with PD have lower cholesterol or that their cholesterol was decreasing at a faster rate than the people who didn't have PD."

As for the link between statins and PD, Wolozin says he presented data at a recent Alzheimer's meeting also showing a "robust" link between statin use and reduced PD—his study is currently under review for publication.

A "relatively simple" hypothesis explains the link, he suggests.

"Statins inhibit cholesterol production; if you inhibit cholesterol production enough, you also inhibit inflammation, and inflammation is probably linked to almost every disease. So statins are a pretty safe pill that do have some side effects, but less than most. And because of their ability to inhibit inflammation they do a fair bit of good."

  1. Huang X, Chen H, Miller WC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov Disord 2006; DOI: 10.1002/mds.21290. Available at: https://www.interscience.wiley.com.

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