Statin therapy prevents the onset of Parkinson disease in patients with diabetes

Abstract

Objective: We studied the association between the statin dosage and the risk of Parkinson disease (PD) in diabetic patients in Taiwan. Methods: One million patients were randomly sampled from a National Health Insurance (NHI) database and followed from 2001 to 2008. Diabetic patients were screened by diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and statin dosage was determined according to the NHI pharmacy database. PD was diagnosed on the basis of ICD-9-CM codes and anti-Parkinson medication use. Statin users was classified by statin dose-duration-day > 28 and matched with nonusers of statins using a coarsened exact matching method. There were 50,432 patients, and half of them were statin users. We examined the risk of PD between statin users and nonusers of statins and further tested the trends of the relative risk between the statin dosage and PD. Results: The PD incidence rate was lower in statin users than in nonusers of statins. The crude hazard ratio of PD incidence in statin users was 0.65 (95% confidence interval [CI] 5 0.57-0.74) in females and 0.60 (95% CI 5 0.51-0.69) in males compared with nonusers of statins. After Cox regression analysis, all statins except lovastatin exerted protective effects on PD incidence and had a significant dose-dependent trend. Interpretation: In Taiwanese diabetic patients, the risk of PD is lower in statin users than in nonusers of statins. Statin users, except lovastatin users, are dose-dependently associated with a decreased incidence of PD compared with nonusers of statins. This finding provides a new indication for statin beyond lipid control and cardiovascular events in diabetic patients. ANN NEUROL 2016;80:532-540 P arkinson disease (PD) is the second most common neurodegenerative disease. It causes irreversible, progressive disability that is characterized by muscle rigidity, slowing of physical movements, behavioral abnormalities, and autonomic impairments. 1,2 PD causes progressive disability and imposes a burden on patients and their families. The etiology of PD is inconclusive but is associated with multiple factors, such as genetic variety, oxidative stress, and progressive neuroinflammation. 3 According to recent reports, diabetes mellitus (DM) and elevated cardiovascular risk factors might play a role in the development of PD. 4-6 Some studies on animal and human models have indicated that tumor necrosis factora, nitric oxide, inducible nitric oxide synthase (iNOS), and oxygen-derived free radicals play a role in the development of PD. 3,7,8 Statin is a competitive 3-hydroxy-3-methylglutarylcoenzyme A reductase competitive inhibitor and is widely used for treating hypercholesterolemia, particularly for maintaining low-density lipoprotein (LDL) cholesterol View this article online at wileyonlinelibrary.com.

Exploring the Association between Statin Use and the Risk of Parkinson’s Disease: A Meta-Analysis of Observational Studies

“…Of the included studies, 6were from North America [14, 18-20, 22, 26] 4 were from Europe [8, 9, 17, 24], and 3 were from Asia [21, 23, 25]. The year of publication ranged from 2007 to 2016, thus spanning 10 years.…”

“…However, only 5 observational studies mentioned about individual statin use such as simvastatin and atorvastatin and other statin [8, 18, 23, 24, 26]. A total of 4,877,059 study subjects were included in our quantitative synthesis of which 1,269,095 and 1,243,616 were men and women respectively; the discrepancy in these numbers is due to 2 studies, which did not contain information on gender [17, 18].…”

Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2–ARE pathway

“…Greater than 50% of subjects participating in clinical trials of Alzheimer's disease are positive for ApoE4 [17]. Similarly, two meta-analyses have reported a correlation between statin therapy and a reduced risk in the development of Parkinson's disease [18,19]. Rosuvastatin, a widely prescribed HMG-CoA reductase inhibitor, has been used for the treatment of dyslipidemia (LDL-C) and has been proven to be more effective in comparison to other members of its class [20].…”

Simvastatin is associated with decreased risk of Parkinson disease

“…Lin and colleagues recently reported that among Taiwanese diabetic patients, statin use was associated with reduced risk of Parkinson disease (PD) . In their study, patients were randomly sampled from a National Health Insurance (NHI) database with follow‐up time from 2001 to 2008.…”