Parkinson's Disease Progression and Statins: Hydrophobicity Matters

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.