Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA.
Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA.
J Parkinsons Dis. 2022;12(3):821-830. doi: 10.3233/JPD-212819.
Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson's disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance.
Investigate a potential effect of statins on PD progression.
Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participating in the PD Biomarker Program (PDBP, 2012-2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the "on" drug state. R2* values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions.
Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2* (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= -7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2* did not reach statistical significance (β= 2.5, p = 0.24).
This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.
最近使用疏水性他汀类药物的随机临床试验报告称，其对帕金森病（PD）的临床进展没有影响。疏水性是影响血脑屏障通透性的关键决定因素。
研究他汀类药物对 PD 进展的潜在影响。
在我们的研究中心参与 PD 生物标志物计划（PDBP，2012-2015 年）的 125 例 PD 患者中，根据疏水性在基线时确定他汀类药物的使用情况，并进行亚型分类。在基线和 18 个月时获得临床（N=125）和易感性 MRI（N=86）数据。使用运动障碍协会统一 PD 评定量表跟踪非运动（MDS-UPDRS-I）和运动（MDS-UPDRS-II）症状以及处于“开”药状态的患者的基于评定者的评分（MDS-UPDRS-III）。使用 R2* 值捕获黑质的病理性进展。使用线性混合效应回归评估他汀类药物使用、其亚型与 PD 进展之间的关系。
与他汀类药物非使用者相比，总体他汀类药物或亲脂性他汀类药物使用并未显著影响 PD 的临床或影像学进展。然而，亲水性他汀类药物使用者的非运动症状 [MDS-UPDRS-I（β=4.8，p=0.010）] 和黑质 R2*（β=3.7，p=0.043）的临床进展更快。MDS-UPDRS-II（β=3.9，p=0.10）也发现了类似的趋势，但基于评定者的 MDS-UPDRS-III（β=-7.3，p=0.10）则呈现相反的趋势。与亲脂性他汀类药物使用者相比，亲水性他汀类药物使用者的非运动症状临床进展也更快[MDS-UPDRS-I（β=5.0，p=0.020）]，但 R2* 未达到统计学意义（β=2.5，p=0.24）。
这项研究表明，亲水性而非亲脂性他汀类药物可能与 PD 进展更快有关。未来的研究可能具有临床和科学意义。
