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Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.

ABSTRACT: BACKGROUND:Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson's disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression. METHODS:Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CI) were determined for increasing serum cholesterol concentration (in quintiles) for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins). RESULTS:The overall mean cholesterol level was 216 mg/dL (range 100-355). The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95%CI), for each higher quintile (in ascending order) are 0.83 (0.59-1.16); 0.86 (0.61-1.20); 0.84 (0.60-1.18); and 0.75 (0.52-1.09). The HR for one standard deviation (SD) increase?=?0.90 [(0.80-1.01), p for trend?=?0.09]. This trend was found in males (HR per SD?=?0.88 [(0.77-1.00), p for trend?=?0.05], but not in females [HR?=?1.03 (0.81-1.32)]. CONCLUSIONS:This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.

SUBMITTER: Huang X

PROVIDER: S-EPMC3154909 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.

Huang Xuemei X Auinger Peggy P Eberly Shirley S Oakes David D Schwarzschild Michael M Ascherio Alberto A Mailman Richard R Chen Honglei H

PloS one 20110811 8

<h4>Background</h4>Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson's disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression.<h4>Methods</h4>Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants we ...[more]

PMID: 21853051

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Project description:Background: Orthostatic hypotension (OH) in Parkinson's disease (PD) can lead to falls, impair quality of life, and increase mortality. A trajectory analysis of OH could be useful to predict and prevent the hypotension incidence early. Methods: The longitudinal data of 660 patients with PD with disease duration up to 12 years were extracted from an integrated PD database. We used latent class mixed modeling (LCMM) to identify patient subgroups, demonstrating trajectories of changes in orthostatic blood pressure (BP) over time. The optimal number of subgroups was selected by several criteria including the Bayesian Information Criterion. Baseline information comparison between groups and backward stepwise logistic regression were conducted to define the distinguishing characteristics of these subgroups and to investigate the predictors for BP trajectory. Results: We identified three trajectories for each orthostatic change of systolic blood pressure (ΔSBP), namely, Class 1 (i.e., the increasing class) consisted of 18 participants with low ΔSBP that increased continuously during the follow-up; Class 2 (i.e., the low-stable class) consisted of 610 participants with low ΔSBP that remained low throughout the follow-up; and Class 3 (i.e., the high-stable class) consisted of 32 participants with high ΔSBP at baseline that was relatively stable throughout the follow-up. Several parameters differed among subgroups, but only male sex [odds ratio (OR) = 4.687, 95% confidence interval (CI) = 1.024-21.459], lower supine diastolic blood pressure (DBP) (OR = 0.934, 95% CI = 0.876-0.996), and lower level of total protein at baseline (OR = 0.812, 95% CI = 0.700-0.941) were significant predictors of an increasing ΔSBP trajectory. Conclusion: This study provides new information on the longitudinal development of ΔSBP in patients with PD with distinct trajectories of rapidly increasing, low-stable, and high-stable class. The parameters such as male sex, lower supine DBP, and lower total proteins help to identify the rapidly increasing class.

Project description:BackgroundThe immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD.MethodsSerum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale - part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated.ResultsTNF-?, IL1-?, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P ? 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P < 0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed "anti-inflammatory" component score was the strongest predictor of slower motor progression (? = -0.22, P = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (? = -0.175, P = 0.007).ConclusionsSerum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.

Publications

Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.

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