Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease

Abstract

The apolipoprotein E (APOE) ε2 allele has been associated with both Parkinson's disease (PD) and lower low density lipoprotein cholesterol (LDL-C). The study is to test the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 110 controls, the PD cases recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and controls recruited from the spouse populations of the same clinic. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterollowering agents. Lower LDL-C concentrations were associated with a higher prevalence of PD. Compared with participants with the highest LDL-C (≥139 mg/dL), the OR was 2.2 (95% CI 0.9-5.1) for participants with LDL-C of 115-138, 3.5 (95% CI 1.6-8.1) for LDL-C of 93-114, and 2.6 (95% CI 1.1 -5.9) for LDL-C ≤ 92. Interestingly, use of cholesterol lowering drugs or just statins was related to lower PD prevalence. Our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence; either of which findings warrant further investigations. KeywordsParkinson's disease; LDL cholesterol; apolipoprotein E; statin; case control study Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder affecting 1-2% of the population over the age of 60 years. The lifetime risk for PD is higher in men than in women. 1 Although a few PD cases are due to several known genetic mutations, the disorder is largely idiopathic, and likely involves interactions of the genome and the environment 2 .The role of apolipoprotein (APOE) in Alzheimer's disease (AD), another age-related neurodegenerative disease, has been elucidated in the past decade. It is generally believed that the ε4 allele is a major susceptibility gene, whereas the ε2 allele is protective for AD and possibly other neurological disorders see review 3 . A recent systematic review, however, Previous epidemiological evidence on dietary fats/cholesterol and PD risk has not been consistent. 10;11 Further, these studies are not directly relevant to the potential role of cholesterol in PD etiology, as non-dietary factors may play more important roles in regulating serum lipid levels. For example, the APOE ε4 allele has been associated with higher low density lipid cholesterol (LDL-C), whereas the ε2 allele has been consistently associated with lower plasma LDL-C. 12;13 Interestingly, there has been one published abstract reporting lower plasma cholesterol concentrations in PD patients than in controls. 14 Further, Musanti et al. 15 reported dramatically lower cholesterol biosynthesis in PD patients than in controls, although there has been no subsequent follow up on this association. The above evidence, coupled with the association between ε2 and PD, led us to test hypothesis that lower serum LDL-C may be ass...

Statin use and the risk of Parkinson disease

“…16 Interestingly, the only previous study to examine associations between statins and prevalent PD also reported a protective effect, even after adjustment for LDL-C concentration. 4 However this study heavily relied on statin use for the post-diagnosis period and prevalent PD cases with a moderately to long duration of disease. Post-diagnosis statin use may not properly reflect pre-diagnosis use.…”

“…2,3 Two studies reporting an association between low cholesterol and PD suggest that low cholesterol or low Co-enyzme Q10 increase the risk of Parkinson's disease (PD) thus raising the possibility that statin use might be harmful to the dopaminnergic system. 4,5 On the other hand there is considerable biological evidence suggesting that statins have neuroprotective properties. Statins scavenge oxygen-derived free radicals, which studies suggest may help ameliorate free radical injury.…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…However, for high serum triglycerides, the multivariate analyses showed lower PD risk (OR 0.49, 95% CI 0.27-0.89) [631]. A hospital-based case-control study, in which spouses of patients from a movement disorder clinic were used as controls, reported increased PD risk with lower serum low-density lipoprotein (LDL) cholesterol (OR for lowest category versus highest 2.6, 95% CI 1.1-6.0), but no significant association for total and high-density lipoprotein (HDL) cholesterol [638].…”

The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns

“…A strong association between lower cholesterol and Parkinson disease risk has been reported, such that each mmol/L increase in total cholesterol was accompanied by a 23% decrease in the risk of developing Parkinson disease. The risk reduction was significant in women but not in men [24].…”