Blood Cholesterol Decreases as Parkinson's Disease Develops and Progresses

Background: Literature shows an inverse association of circulating cholesterol level with the risk of Parkinson's disease (PD); this finding has important ramifications, but its interpretation has been debated. Objective: To longitudinally examine how blood total cholesterol changes during the development of PD. Methods: In the Health, Aging and Body Composition study (n = 3,053, 73.6±2.9 years), blood total cholesterol was measured at clinic visit years 1, 2, 4, 6, 8, 10, and 11. We first examined baseline cholesterol in relation to PD risk, adjusting for potential confounders and competing risk of death. Then, by contrasting the observed with expected cholesterol levels, we examined the trajectory of changes in total cholesterol before and after disease diagnosis. Results: Compared to the lowest tertile of baseline total cholesterol, the cumulative incidence ratio of PD and 95% confidence interval was 0.41 (0.20, 0.86) for the second tertile, and 0.69 (0.35, 1.35) for the third tertile. In the analysis that examined change of total cholesterol level before and after PD diagnosis, we found that its level began to decrease in the prodromal stage of PD and became statistically lower than the expected values ∼4 years before disease diagnosis (observed-expected difference, -6.68 mg/dL (95% confidence interval: -13.14, -0.22)). The decreasing trend persisted thereafter; by year-6 post-diagnosis, the difference increased to -13.59 mg/dL (95% confidence interval: -22.12, -5.06), although the linear trend did not reach statistical significance (p = 0.10). Conclusion: Circulating total cholesterol began to decrease in the prodromal stage of PD, which may in part explain its reported inverse association with PD.