SEATTLE – Statin use was associated with protection against the development of Parkinson’s disease in a population-based historical cohort study of 94,308 middle-aged and older adults in Israel.

Statin users, who accounted for one-third of the cohort, had a 27% lower risk of Parkinson’s disease (PD), compared with nonusers, after accounting for potential confounders.

"Statins, in addition to lowering cholesterol levels and reducing cardiovascular risk, may have a protective effect on the incidence" of PD, lead investigator Dr. Amnon Lahad said at the annual meeting of the North American Primary Care Research Group.

PD, which is a central nervous system degenerative disease, "may react like other cardiovascular diseases in responding to statins," he said, speculating that ischemia plays a role in its pathogenesis, much as it does for dementia. "It is probably at the level of the microvasculature. We don’t really know how to test [for it], but it’s there."

About half a dozen studies have assessed the association between statins and PD in recent years, but their conclusions have been inconsistent. Most have found that statin use confers increased risk, with a subset suggesting that this association is mediated through cholesterol levels, making statins simply a confounder, according to Dr. Lahad, chairman of the department of family medicine at the Hebrew University of Jerusalem.

In the study, he and his colleagues searched the database of the largest health maintenance organization in Israel to identify all patients older than 45 years in a single administrative region during 2001-2007.

They excluded patients who had PD or took statins before the study period, used neuroleptic drugs at any time, changed health insurance, or did not have a record of LDL cholesterol values.

Statin use and chronic illnesses were also ascertained from the database. Family history on PD was not available, and body mass index was not used because it was inconsistently recorded, according to Dr. Lahad.

Analyses were based on 94,308 patients, he reported. The cohort was nearly equally divided by sex. About a fifth of patients had low socioeconomic status, as indicated in the database by the waiving of their copayment for prescriptions.

Substantial proportions of the cohort smoked (20%) and had diabetes (22%), hypertension (51%), or ischemic heart disease (19%), or had previously experienced a stroke (8%).

Some 32% of the patients were classified as statin users because they filled at least six monthly statin prescriptions during a 9-month period. The rest were classified as nonusers.

Overall, 1.1% of the cohort developed PD during the study period, as ascertained from their filling of at least two monthly prescriptions for an antiparkinsonian medication.

In a Cox regression analysis, the risk of PD was elevated for men compared with women (hazard ratio, 1.57; P less than .0001), for patients with low socioeconomic status compared with their better-off peers (HR, 1.33; P less than .0001), and for patients who had experienced a stroke compared with those who had not (HR, 1.96; P less than .0001).

"Surprisingly, the other diseases or conditions [hypertension, ischemic heart disease, diabetes, and smoking] were not related, even in a pretty big group," to PD, Dr. Lahad said. "The most surprising is smoking, which in the literature is connected."

LDL cholesterol level at baseline was not significantly associated with the risk of PD. However, there was a trend for an increased risk of PD with an LDL level greater than 100 mg/dL, as well as a lower risk of the disease in individuals with LDL levels greater than about 160 mg/dL.

When statin use was added to the analysis, statin users had about a one-fourth reduction in the risk of PD relative to nonusers (HR, 0.73; P = .001), and the other significant associations persisted.

However, when the investigators accounted for statin use, the individuals with the highest LDL cholesterol levels no longer had a reduced risk of the disease. "It probably was the effect that this group got statins much more often, so it did protect them," Dr. Lahad speculated. "And it showed, without the statin, purely the effect of the cholesterol."

The risk of PD fell with an increasing duration of statin use (as assessed from the number of prescriptions and months of use). But in this case, the association was weaker. "It was a trend; it wasn’t by itself significant," he noted.

"Of course, it’s not a randomized controlled trial," Dr. Lahad acknowledged, so it is possible that other factors explain the observed association. "But at least we don’t find the alarming finding of previous studies that show that statins are connected to an increase in morbidity."

Dr. Lahad reported that he had no relevant conflicts of interest.

Statin Use Reduced Risk of Parkinson's in Cohort Study