Serum Cholesterol Levels and the Risk of Parkinson's Disease

Abstract

Several recent findings suggest a role of lipid and cholesterol metabolism in the pathogenesis of Parkinson's disease. Therefore, the authors examined the association between serum levels of cholesterol and the risk of Parkinson's disease in the prospective, population-based Rotterdam Study among 6,465 subjects aged 55 or more years with repeated in-person examination and on average 9.4 years of follow-up (1990-2004). Higher serum levels of total cholesterol were associated with a significantly decreased risk of Parkinson's disease (age- and sex-adjusted hazard ratio per mmol/liter increase in cholesterol = 0.77, 95% confidence interval: 0.64, 0.94), with evidence for a dose-effect relation. The association was restricted to women and remained unchanged after adjustment for multiple potential confounders. These findings may indicate a role of lipids in the pathogenesis of Parkinson's disease. Alternatively, they could reflect the strong correlation-especially in women-between levels of serum cholesterol and the antioxidant coenzyme Q10. If confirmed, this would provide further support for an important role of oxidative stress in the pathogenesis of Parkinson's disease.

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

“…The larger Nurses Health Study and Health Professionals Follow-up Study (in total 530 incident PD cases) found no association between self-reported high cholesterol and PD [634]. However, similar to the Rotterdam study [640], a trend of decreasing PD risk with increasing levels of self-reported total serum cholesterol was observed that was significant in women (p for trend 0.04) but not in men (p for trend 0.19) [634]. In contrast, a…”

“…The Rotterdam study also found that high serum total cholesterol was associated with lower PD risk; the association was, however, observed only in women (RR per mmol increase in cholesterol 0.59, 95% CI 0.45-0.78 in women; 1.01, 95% CI 0.78-1.30 in men) [640]. No association was observed for HDL cholesterol [640]. The larger Nurses Health Study and Health Professionals Follow-up Study (in total 530 incident PD cases) found no association between self-reported high cholesterol and PD [634].…”

“…The Rotterdam study also found that high serum total cholesterol was associated with lower PD risk; the association was, however, observed only in women (RR per mmol increase in cholesterol 0.59, 95% CI 0.45-0.78 in women; 1.01, 95% CI 0.78-1.30 in men) [640]. No association was observed for HDL cholesterol [640].…”

SERUM LIPIDS AND Lp-PLA2 ACTIVITY IN MULTIPLE SCLEROSIS

“…Impaired cholesterol homeostasis in serum and brain has been linked to chronic neurodegenerative disorders including Alzheimer's disease, Huntington's disease, Parkinson's disease, Niemann-Pick type C disease and Smith-Lemli Opitz syndrome [9]. There is now emerging evidence indicating that dyslipidaemia is associated with MS disease progression.…”

“Hot Spots” in Medicinal Chemistry

“…[33,34] Cerebral and serum cholesterol levels follow different metabolic pathways and are only indirectly connected; [34] nevertheless, an inverse correlation between serum cholesterol levels and incidence of Parkinson's disease (PD) was reported in epidemiological studies. [35][36][37] The consumption of polyunsaturated fatty acids (PUFAs) may have protective effects against chronic inflammation [38] and improve cholinergic transmission in the brain. [39] Furthermore, the cerebral levels and chain lengths of PUFAs [40] as well as of sphingolipids [41] play a role in the maintenance of the plasticity of the neuronal network, the derangement of which is closely associated with several neurodegenerative diseases including AD and PD.…”