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Delaying Parkinson’s Disease Onset with Statin Therapy

Can statins provide neuroprotective properties in diabetes patients?

The use of statins has been widely implemented in the management of hyperlipidemia, diabetes, and other cardiovascular disease. Studies have shown benefits from the medications that go beyond their ability to inhibit the rate-limiting step in cholesterol biosynthesis. This inhibitory effect has made these agents a pivotal part of maintaining LDL-C levels in patients with type 2 diabetes mellitus. Statins have shown to provide anti-inflammatory and antioxidant effects in the vascular endothelium, which have made this class of medications useful for preventing vascular injury and reducing atherosclerosis risk. Based on these findings, researchers have been studying the use of statins in Parkinson’s Disease (PD). A meta-analysis conducted by Shuang Bai et al., looked in the use of statins and the risk of Parkinson’s Disease. In this study, researchers found that statin use (i.e. lovastatin, simvastatin, pravastatin, atorvastatin, and rosuvastatin) is associated with a reduced risk of Parkinson’s Disease. From the different statins used in this study, it was discovered that simvastatin and atorvastatin provided the most benefit in the risk of developing Parkinson’s Disease due to their lipophilicity and ability to readily cross the blood-brain barrier.

Pravastatin showed least benefit due to its lipophilicity and inability to cross the blood-brain barrier when compared to atorvastatin and simvastatin. Findings from this and other studies show conflicting data, which warranted more research to further highlight the potential benefits from statin therapy in PD patients.

Recently, K.D. Lin and colleagues expanded on this topic and looked at the association between the use of statins and onset of Parkinson’s Disease in diabetes patients. A total of 50,432 patients were enrolled in the study. Diagnosis of diabetes was established by the use of ICD-9-CM codes. Those patients who had 3 outpatient visits within the follow-up year were assigned to the diabetes group. The study took into consideration other comorbidities, such as hypertension, hyperlipidemia, ischemic heart disease, and stroke. Patients were followed for 7.84 ± 3.79 years. From the study subjects, 76.28% were diagnosed with hypertension, out of which 54.02% were statin users. A total of 69.13% were diagnosed with hyperlipidemia and only 64.23% were statin users. Subsequently, stroke was the diagnosis for 28.14% of patients and an ischemic heart disease diagnosis was established for 39.59% of patients, out of which 53.29% and 56.91% were on statin therapy, respectively.

Results from this research study show a lower incidence rate of Parkinson’s Disease in those patients receiving statin therapy (crude HR: 0.63; 95% CI 0.57-0.69; p<0.001 based on dose-dependent trends). A regression analysis showed a higher RR in the incidence of PD in patients diagnosed with stroke (crude HR: 1.78; 95% CI 1.60-2.00). This can be explained by the neurological damages a stroke can cause in the patient.  It was also found that older patients, those with low socioeconomic status, and patients with hyperlipidemia and no statin use were at an increased risk for Parkinson’s Disease. Another finding from this study shows that all statins except lovastatin demonstrated protective effects on PD incidence, which may be attributed to their pharmacological properties.

These findings can support the use of statins in diabetes patients who are at risk for PD. Even though there is evidence supporting the use of statins in Parkinson’s Disease, some of the results seem inconclusive. Some limitations from this study include the fact it did not take into consideration confounding factors, such as nutrition status, alcohol use, and smoking/nicotine levels. Additionally, the study did not look into specific laboratory values for lipid levels, which have been shown to be inversely proportional with the incidence of Parkinson’s Disease. These characteristics can help guide future studies in a more diverse population, which includes all of these variables, therefore making it more applicable to our patient population. Nonetheless, the current evidence shows that statin therapy can have protective effects in the substantia nigra, in addition to attenuating glial activation, inhibiting neuronal inflammatory process, promoting antioxidant pathways, and providing protection to dopaminergic neurons.

Practice Pearls:

  • Statins have the potential of decreasing the onset of Parkinson’s Disease in diabetes patients through neuroprotective effects.
  • Statin therapy with lovastatin provides least benefit in delaying the onset of Parkinson’s Disease in diabetes patients when compared to other statins.
  • More studies are needed in order to establish the exact response from statins in patients with Parkinson’s Disease

References:

Bai, Shuang, Yi Song, Xin Huang, Lidan Peng, Jie Jia, Yu Liu, and Hong Lu. “Statin Use and the Risk of Parkinson’s Disease: An Updated Meta-Analysis.” PLOS ONE PLoS ONE 11.3 (2016): n. pag. Web

Lin KD, Yang CY, Lee MY, Ho SC, Liu CK, Shin SJ. “Statin Therapy Prevents the Onset of Parkinson Disease in Patients with Diabetes” Ann Neurol. (2016). Web. doi: 10.1002/ana.24751. [Epub ahead of print]

 

Researched and prepared by Pablo A. Marrero-Núñez – USF College of Pharmacy Student Delegate – Doctor of Pharmacy Candidate 2017,  reviewed by Dave Joffe, BSPharm, CDE