Parkinson’s Disease Progression and Statins: Hydrophobicity Matters

Article type: Research Article

Authors: Lewis, Mechelle M.^{a; b; 2} | Albertson, Richard M.^{a; 1; 2} | Du, Guangwei^a | Kong, Lan^c | Foy, Andrew^{c; d} | Huang, Xuemei^{a; b; e; f; g; *}

Affiliations: [a] Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [b] Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [c] Department of Public Health Sciences, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [d] Department of Medicine, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [e] Department of Radiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [f] Department of Neurosurgery, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA | [g] Department of Kinesiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA

Correspondence: [*] Correspondence to: Xuemei Huang, MD, PhD, Professor of Neurology, Penn State Hershey Medical Center, 500 University Dr., H-037, Hershey, PA 17033-0850, USA. Tel.: +1 717 531 0003, ext. 287082; Fax: +1 717 531 0266; [email protected]

Note: [1] Current affiliation: UH Internal Medicine Core, University of Michigan, Ann Arbor, MI, USA.

Note: [2] These authors contributed equally to this work.

Abstract: Background: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. Objective:Investigate a potential effect of statins on PD progression. Methods: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. Results: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). Conclusion:This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

Keywords: Parkinson’s disease, lipophilic statins, hydrophilic statins, MDS-UPDRS scores, susceptibility imaging, MRI, substantia nigra, R2^*

DOI: 10.3233/JPD-212819

Journal: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 821-830, 2022