A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease.

BACKGROUND: Recent evidence indicates that lipophilic statins have a neuroprotective benefit in animal models of Parkinson's disease (PD). The objective of this study was to evaluate whether lovastatin has the potential to slow motor symptom progression in patients with early-stage PD. METHODS: This double-blind, randomized, placebo-controlled trial enrolled 77 patients with early-stage PD between May 23, 2017, and July 12, 2018, with follow-up ending September 1, 2019. Lovastatin 80 mg/day or placebo with 1:1 randomization was administered for 48 weeks. Mean change in the parts I-III scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), changes in the striatal dopamine uptake ratio measured by 18 F-dopa PET scan, and changes in PD medications between baseline and the week 48 visit were measured. RESULTS: Of the 77 randomized patients, 70 (90.9%) completed the study. There was a slightly beneficial trend of the MDS-UPDRS motor score in the lovastatin group (-3.18 ± 5.50) compared with the placebo group (-0.50 ± 6.11); P = 0.14 adjusted for age, sex, disease duration, and baseline LEDD. Mean percentage change in the striatal 18 F-dopa uptake ratio deteriorated less in the lovastatin group than in the placebo group on the dominant side of caudate (1.2% ± 7.3% vs -7.1% ± 8.2%, P < 0.01) and putamen (2.3% ± 7.1% vs -6.4% ± 8.1%, P < 0.01). We found no between-group differences in the change in part I or part II MDS-UPDRS scores. Lovastatin was generally well tolerated. CONCLUSIONS: Lovastatin treatment in patients with early-stage PD was associated with a trend of less motor symptom worsening and was well tolerated. A future larger long-term follow-up study is needed to confirm our findings. © 2021 International Parkinson and Movement Disorder Society.

Upregulation of cluster of differentiation 36 mRNA expression in peripheral blood mononuclear cells correlates with frailty severity in older adults.

BACKGROUND: Aging-associated frailty has been connected to low-grade chronic inflammation and also to progressive monocytic activation. CD36 (cluster of differentiation 36, platelet glycoprotein 4 or fatty acid translocase) has been shown to induce the expression of pro-inflammatory cytokines and to activate macrophage connected inflammation. This study aims to examine whether the expression of CD36 is up-regulated among frail older adults. METHODS: The demographic data, Fried Frailty Index, metabolic and inflammatory parameters of our observational study were obtained from the comprehensive geriatric assessment programme of a hospital-based outpatient department. The mRNA isolated from the peripheral blood mononuclear cells (PBMCs) was used to determine the levels of CD36, tumour necrosis factor alpha (TNF-α), and CXC chemokine ligand-10 (CXCL10) mRNAs with real-time polymerase chain reaction (PCR). RESULTS: A total of 189 older adults (58% female) were included in the analysis, and the mean age was 77.19 ± 6.12 years. The numbers of participants who fitted in the groups of robust, pre-frail, and frail were 46, 106, and 37, respectively. Our data showed that CD36 mRNA expression levels in PBMCs were the highest in the frail group (1.25 ± 0.53 in robust, 2.13 ± 1.02 in pre-frail, and 2.78 ± 1.15 in frail group, P < 0.001). Further regression analyses revealed that CD36 mRNA levels were positively correlated with both the pre-frail and frailty status in the univariate analysis (both P's < 0.001). What might suggest something worthy of further investigation is that, with potential confounders being adjusted for, CD36 remained as an independent factor that positively correlated with the pre-frail and frailty status in the multivariable analysis (P < 0.001). CONCLUSIONS: CD36 mRNA levels in PBMCs in robust older adults are significantly lower than in pre-frail and in frail. Our findings suggest that CD36 mRNA levels in PBMCs may be considered a potential biomarker for frail severity.

Confidence limits for conformance proportions in normal mixture models.

Conformance proportions are important numerical indices for quality assessments. When the population is characterized by a normal mixture model, estimating conformance proportions can be a practical issue. To account for the inherent structure of normal mixture models, universal and individual conformance proportions are first defined for the purpose of evaluating the overall population and specific subpopulations of interest, respectively. On the basis of generalized fiducial quantities, a systematic method is then proposed in this paper to obtain confidence limits for the two classes of conformance proportions. The simulation results demonstrate that the proposed method can maintain the empirical coverage rate sufficiently close to the nominal level. In addition, two examples are given to illustrate the proposed method.