Adults who regularly take aspirin NSAIDs have a decreased risk of Parkinson’s disease compared with controls, researchers reported in the November 6 Neurology. An even stronger effect was observed among regular nonaspirin NSAID users, according to lead investigator Beate Ritz, MD, PhD, and colleagues.

The investigators found that risk of Parkinson’s disease among regular nonaspirin NSAID users was 48% lower than in controls and 56% lower for those who reported two or more years of use. Regular use of aspirin was protective only for women, especially among long-term regular users. However, Dr. Ritz told Neurology Reviews that she suspects this is because the researchers asked about numbers of tablets taken per week, and men may be more likely to take the low-dose aspirin tablets commonly recommended for cardiovascular protection. These would not provide the anti-inflammatory effect thought to be the reason for the neuroprotection in women, who were 49% less likely to develop Parkinson’s disease if they reported more than two years of regular aspirin use. “Overall, we found that nonaspirin NSAIDs and aspirin were associated with up to a 40% to 50% decrease in the risk of Parkinson’s disease in regular users,” said Dr. Ritz, who is a Professor of Epidemiology at the University of California, Los Angeles.

A PROTECTIVE ROLE FOR NSAIDS

The study included 293 patients with Parkinson’s disease and 286 age-, race-, and gender-matched controls. Participants were asked if they had taken, at any point in their lifetime, a number of different types of aspirin or nonaspirin NSAIDs once a week or more for at least one month. They were also asked about the number of pills taken per day or week, the length of treatment by month or year, and the age at first and last use of each drug.

The odds ratios for developing Parkinson’s disease were 0.80 for regular (at least two pills per week for at least one month) aspirin users, 0.52 for regular nonaspirin NSAID users, 0.44 for nonaspirin NSAID users of at least two years, and 0.51 for women with long-term aspirin use.

Dr. Ritz related that the connection to apparent protection against Parkinson’s disease was a serendipitous finding in a study designed to simply document lifetime use of analgesics. “We were just asking about painkiller use,” she said. She theorized that the link to Parkinson’s disease became apparent, because, unlike prior case-control studies, this study included lifetime use (compared with only five to seven years before disease onset) and did not rely on prescription data. “Most of this use is not for prescription drugs,” she pointed out.
The duration of use required to produce the apparent protective effect is unknown, but Dr. Ritz predicted that “regular use of these medications at age 30 to 50, long before the diagnosis of Parkinson’s disease,” may be important.

“A protective role for NSAIDs is biologically plausible, although an understanding of the exact mechanism of NSAIDs’ potential protective effect remains elusive,” the authors wrote. “NSAIDs may exert their anti-inflammatory effect by inhibiting proinflammatory cyclooxygenase (COX) enzymes, which have been implicated in the pathogenesis of Parkinson’s disease. COX-2 is upregulated in the dopaminergic neurons of both patients with Parkinson’s disease and mouse models of Parkinson’s disease.... NSAIDs may also protect against reactive oxidative species or protect neurons from glutamate-induced toxicity by inhibiting the activation of nuclear factor-kB.”

In addition, said Dr. Ritz, “Other studies have shown that inflammatory markers are associated with increased rates of Parkinson’s disease. Inflammation contributes to brain death in the regions affected in Parkinson’s disease. The process may be that cells die, which induces microglia, which leads to a chronic inflammatory process and more nerve cell death. There is probably a subgroup of people who are inherently more vulnerable, in whom inflammation triggers development or progression of Parkinson’s disease. If we could find ways to identify people at risk, using biomarkers, family history, or other factors, it might be possible to develop a protective strategy based on anti-inflammatory drugs.” Dr. Ritz noted that validating such an approach would be difficult. “It will require identifying currently healthy people who are at increased risk for Parkinson’s disease, randomizing them to NSAIDs or aspirin at certain doses versus placebo, and treating them in their 40s for a disease they would not be diagnosed with typically until in their 60s,” she said.

OPTIMIZING TREATMENT IN PATIENTS

However, there is little downside risk to routine use of a few tablets of NSAIDs or aspirin per week, Dr. Ritz pointed out. “If you’re really worried about Parkinson’s disease, maybe this is an alternative,” she said. “If the patient has a risk profile, such as family history, and no indications of risk for gastrointestinal bleeding or other NSAID-related side effects, why not?” Dr. Ritz and colleagues are conducting a study in Denmark that will include 2,000 to 3,000 patients with Parkinson’s disease and 30,000 matched case-control subjects, drawing data on lifetime use of analgesics of all types from the Danish national health system and pharmacy databases. The researchers expect to report data on Parkinson’s disease rates and prescription analgesic use early next year and on lifetime use of all analgesics (which requires in-depth interviews with patients and controls) in about two years.

NR

—Janis Kelly

Suggested Reading
Bornebroek M, de Lau LM, Haag MD, et al. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Neuroepidemiology. 2007;28(4):193-196.
Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology. 2007;69(19):1836-1842.

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