Regular users of statins had a “marginally significant” lower risk of developing Parkinson’s disease than did nonusers in a prospective, observational analysis of two large, ongoing study cohorts.

The protective effect was stronger at ages younger than 60 years than at older ages, Dr. Xiang Gao and his associates reported March 12 in Archives of Neurology. Dr. Gao is in the department of nutrition at Harvard University School of Public Health and the department of epidemiology at Brigham and Women’s Hospital, both in Boston.

Dr. Xiang Gao

The study builds on several previous studies that examined the association between statin use and Parkinson’s disease (PD), but did not control for important confounders such as smoking status and caffeine intake. Given the mixed results of those studies, Dr. Gao and his colleagues advised that the marginal significance of current study’s results should be interpreted with caution and noted that further study is needed.

Statins have potent anti-inflammatory and immunomodulating effects that could be neuroprotective, but they also may lower levels of coenzyme Q, which is itself neuroprotective and is being investigated as a possible treatment for PD, the researchers said.

They assessed 90,874 women in the Nurses Health Study who were aged 30-55 years at baseline in 1976 and 38,192 men in the Health Professionals Follow-Up Study who were aged 40-75 years at baseline in 1986. In both studies, subjects updated their health information by way of questionnaires every 2 years.

During an average of 12 years of follow-up, 644 incident cases of PD developed in 338 women and 306 men. The incidence of PD was lower in statin users than in nonusers, with a pooled relative risk of PD of 0.74, the investigators reported (Arch. Neurol. 2012;69:380-4).

This association did not change when the data were adjusted to account for potential confounders such as subject age, smoking status, caffeine consumption, lactose intake, use of ibuprofen, duration of hypercholesterolemia, and comorbidities. It also remained robust when the analysis was restricted only to subjects whose PD had been confirmed by a neurologist, as well as in a sensitivity analysis that took into account the duration of statin use.

There was a significant interaction between statin use and subject age with regard to PD risk. The association between statin use and the risk of PD was significant only in those who were aged 60 years or younger at the beginning of follow-up, according to Dr. Gao and his colleagues.

These findings are consistent with the results of animal and in-vitro studies “which suggest that statins could reduce alpha-synuclein accumulation and oxidative stress, suppress cyclooxygenase 2 expression, reduce release of TNF-alpha and nuclear factor kappaB activation, activate peroxisome proliferator-activated receptor-gamma, and up-regulate dopamine D1 and D2 receptors in the brain,” they added.

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