Statins, plasma cholesterol, and risk of Parkinson's disease: A prospective study

Abstract

Background Previous findings on the association of statins, plasma lipids, and Parkinson’s disease are confounded by the fact that statins also affect lipid profiles. We prospectively examined plasma lipids and statin use in relation to Parkinson’s disease in the Atherosclerosis Risk in Communities (ARIC) Study. Methods Statin use and plasma lipids were assessed at baseline (Visit 1, 1987–89) and at three triennial visits thereafter (Visits 2–4) until 1998. Potential Parkinson’s cases were identified from multiple sources and validated where possible. The primary analysis was limited to incident Parkinson’s cases diagnosed between 1998 and 2008. Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Results Statin use was rare at baseline (0.57%) but increased to 11.2% at Visit 4. During this time frame, total-cholesterol levels decreased, particularly among statin users. Fifty-six Parkinson’s cases were identified after 1998. Statin use before 1998 was associated with significantly higher Parkinson’s risk after 1998 (Odds ratio = 2.39, 95% Confidence interval 1.11–5.13) after adjusting for total-cholesterol and other confounders. Conversely, higher total-cholesterol was associated with lower risk for Parkinson’s after adjustment for statin usage and confounders. Compared to the lowest tertile of average total-cholesterol, the odds ratios for Parkinson’s were 0.56 (0.30–1.04) for the second and 0.43 (0.22–0.87) for the third tertile (Ptrend=0.02). Conclusions Statin use may be associated with a higher Parkinson’s risk, whereas higher total cholesterol may be associated with lower risk. These data are inconsistent with the hypothesis that statins are protective against Parkinson’s disease.

Associations between 18F-AV133 Cerebral VMAT2 Binding and Plasma LDL and HDL Levels in Parkinson’s Disease

“…Based on the present results, high serum lipid levels may have a beneficial effect on improving the monoaminergic neuron integrity and thus slowing PD progression. In addition, the present findings suggest that lowering plasma cholesterol with statins should be considered cautiously in PD patients, as has been indicated by Huang et al [17]. Their study showed that statin usage was associated with higher risk of PD after accounting for serum LDL-cholesterol levels, which is inconsistent with the hypothesis that statins might be neuroprotective for PD [40].…”

“…Although the findings are still controversial, the overall evidence favors an association between higher total cholesterol and lower PD risk [13,17]. Recent reports revealed a direct relationship between higher cholesterol levels and a slowing in the rate of decline in Parkinson's disease patients [18].…”

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

“…The year of publication ranged from 2007 to 2016, thus spanning 10 years. Six studies were case-control design studies [8, 9, 14, 19, 22, 26], and 7 were cohort studies [17, 18, 20-24]. Eleven studies reported that the age of onset for PD development was over 65 years but 2 studies reported an age of onset below 60 years.…”

“…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.…”

Mitochondrial Quality Control as a Therapeutic Target

“…Instructively, the commercially available statins (e.g., atorvastatin and simvastatin), which lower cholesterol levels by inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have been implicated in neuroprotection against PD, AD, traumatic brain injury, and secondary progressive multiple sclerosis (Kumar et al, 2012;Malkki, 2014). In some instances, neuroprotection has been associated with the lipophilicity of the drug (Haag et al, 2009;Huang et al, 2015), but direct mitochondrial protection is not established either experimentally or clinically, and the well-known adverse effects of statins on mitochondria, such as inhibition of Coenzyme Q synthesis, is an important caveat with these agents (Golomb and Evans, 2008). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors cause a myopathy that has been attributed in part to a reduction in CoQ 10 levels (Potgieter et al, 2013).…”