Stopping Statins May Be Associated with the Development of Parkinson Disease

Summary and Comment |
July 24, 2013

Stopping Statins May Be Associated with the Development of Parkinson Disease

  1. Michael S. Okun, MD

In an observational study, patients who stopped lipophilic (but not hydrophilic) statins had an increased risk for incident PD.

  1. Michael S. Okun, MD

Findings associating statin discontinuation with Parkinson disease (PD) risk have been inconsistent. Now, researchers in Taiwan examined the effect of discontinuing lipid-lowering, statin-based therapy on the incidence of PD. Participants were identified between 2001 and 2008 from the comprehensive National Health Insurance Research Database.

The researchers identified 43,810 statin initiators. The observed incidence of PD was different between lipophilic and hydrophilic statins (1.68 vs. 3.52 per 1,000,000 person-days). Compared with discontinuation, continuation of lipophilic, but not hydrophilic, statins was associated with a decreased risk for incident PD (hazard ratio, 0.42). After adjustment for comorbidities and medications, the results were unchanged. The apparent benefit of continuation was strongest with simvastatin and atorvastatin. This effect was more pronounced in women taking simvastatin (HR, 0.11). Among people taking atorvastatin, those aged 65 or older benefited the most (HR, 0.42). The long-term use of statins was not associated with incident PD.


The mechanism of action for statins as a disease modifier in Parkinson disease and other brain disorders is unknown. However, as this study demonstrates, any drug aimed at a neurodegenerative disease must cross the blood–brain barrier. Once a statin enters the brain, hypothetically it decreases abnormal protein clumps, decreases inflammation, and potentially even modifies the brain's dopaminergic and glutamatergic pathways. The results of this study are intriguing, but not surprising, given that lipophilic statins penetrate the brain. The authors were clever in asking what would happen if you stop a statin, rather than conducting a typical association study.

Study limitations include a relatively small source population, lack of direct information about smoking (which protects against PD), and lack of PD diagnosis by a movement disorders specialist or use of strict criteria. In general, these types of population studies are prone to error and should not be used to make large-scale changes in medical practice. However, at-risk individuals (e.g., those who have a family member with PD) may elect to take a lipophilic statin with the hope of delaying the appearance of PD symptoms. Additionally, for patients currently taking one of these statins, continued use may be advisable (especially for those at increased risk for PD). There is no proven benefit to starting one of these drugs after a formal diagnosis of PD.

Editor Disclosures at Time of Publication

  • Disclosures for Michael S. Okun, MD at time of publication Grant / research support NIH; National Parkinson Foundation; Michael J. Fox Foundation Editorial boards Parkinsonism and Related Disorders; Tremor and Hyperkinetic Disorders Leadership positions in professional societies National Parkinson Foundation (Medical Director and Ask the Doctor Director); Tourette Syndrome Association (Medical Advisory Board)


Reader Comments (9)

Marc Sapir Physician, Family Medicine/General Practice, public clinic

Interesting but as above this PD association is pretty much a zebra on the savannah, mainly of interest in terms of setting the table for other investigations in neurological interactions. I think that recent studies showing statins associated with increases of both hyperglycemia and incident DM (with most statins), and the recent study claiming that previous work has far underestimated the muscle deteriorating impacts of statins are outcomes of far greater concern to clinicians in deciding how to balance risk and benefits--even when we know statins reduce both CHD risk and all cause mortality. I'm moving many patients with DM, hyperglycemia, hypertriglyeridemia and obesity over to pravastatin, even though it's less potent than most because of the glycemia issue.

Michael Okun MD Physician, Neurology, University of Florida

Thank you for the comment. I am the summary author and though this particular paper did not specifically address the glycemia-statin issue, you bring up an important clinical point we should all pay attention to.

David Keller, MD Physician, Internal Medicine, Disabled

Patients with progressive incurable diseases like Parkinson's are often willing to try a possible remedy based on weak evidence if there is little potential for harm. Epidemiological studies involving statins can be confounded by "indication bias", making it difficult to determine whether a benefit was associated with taking the statin, or with a lifetime of elevated lipids which was the indication for taking the statin. If the latter, then hyperlipidemia might be protective against PD (as nicotine may be) and taking a statin might actually worsen matters. This study reduces the worry about indication bias by showing a clear separation between the effects of lipophilic versus hydrophilic statins. Professor Okun states that there is "no proven benefit to starting [a statin] after a formal diagnosis of PD", but neither does this study prove that stopping statin therapy increases the risk of PD. This study merely highlights an association, without demonstrating cause and effect the way a controlled trial could. However, this study has decreased my concerns about indication bias to the point where I will now take simvastatin for the approved indication of improving my lipids, with more confidence that it will not accelerate the progression of my PD, and a justifiable glimmer of hope that it might actually help, while we await a more conclusive prospective controlled trial of simvastatin.

Hourez Physician, Neurology, CHU Charleroi / Belgium

In the absence of distingue by Movement Disorders specialist, could it be that patients treated with lipophilic statins were better protected against vascular lesions/subclinical strokes resulting in less patients with VASCULAR parlinsonism - the connection would BE direct through this mechanism...

Dennis Jay, D.D.S. Other, Dentistry, Retired

Too bad this study did not compare to the incidence of Parkinson's in a group who never did take statins at all.

Paul block md Physician, Urology, Office

Interested to know if the lipophilic statins and their effect on the brain has any effect on Alzheimer's

JAMES RECHT Physician, Psychiatry

I apologize in advance if my question sounds dense, but is it possible that the authors have things backwards, i.e. that PD may in the observed cases actually be caused (or exacerbated) by the statins (and their subsequent withdrawal)? We see an analogous mechanism, for example, in the incidence of rebound anxiety and panic symptoms caused by chronic benzodiazepine therapy followed by benzodiazepine discontinuation. In many cases, the resulting symptoms are significantly more severe than those at initial presentation. I recognize that this may be stretching the analogy a bit -- and I look forward to hearing from those with greater expertise in the area of PD on this issue. Other Healthcare Professional, Pharmacology/Pharmacy

I find articles like this to be more disturbing than helpful. Retrospectively looking at 1 commonality without addressing other risk factors and seeing increases in 1-3 per million seems to be looking for ways to publish rather than really addressing reasonable medical risks/benefits. In this case the assumption of benefits would so far outweigh this risk that this almost belongs in the irrelevant column. It raises the question of whether good science is really going into publications now.

Brian Mahood MA FRACP Physician, Pulmonary Medicine, Retired

Simvastatin has already been shown to decrease recurrences of MS apparently by affecting both the ratio of both types and level of activity of the lymphocytes which cross the blood brain barrier and have been shown be involved in the inflammatory processes in the brain. As noted the sample size is far too small and the study needs to be repeated with an appropriate number of patients to conform that if symptoms increase after cessation that they are 'caused' by an increase in focal inflammation.

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