title: Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1.
abstract: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients.
  
  
  
  To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline.
  
  
  
  The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually.
  
  
  
  1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002).
  
  
  
  Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.
authors.affiliation: Departments of Neurology, Molecular Pharmacology and Physiology, University of South Florida, Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa FL, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
authors.forename: Ruosha
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pérez
authors.affiliation: Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
authors.forename: Xuehan
authors.initials: X
authors.lastname: Ren
authors.affiliation: Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Medical University of South Carolina, Department of Public Health Sciences, Charleston, SC, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Elm
authors.affiliation: Department of Neurology, Michigan State University, East Lansing, MI, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Goudreau
authors.affiliation: National Parkinson Foundation Center of Excellence, Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morgan
authors.affiliation: Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: John Y
authors.initials: JY
authors.lastname: Fang
authors.affiliation: University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Aminoff
authors.affiliation: University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Chadwick W
authors.initials: CW
authors.lastname: Christine
authors.affiliation: The Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Dhall
authors.affiliation: Division of Movement Disorders, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Chizoba C
authors.initials: CC
authors.lastname: Umeh
authors.affiliation: Department of Neurological Sciences, University of Vermont, College of Medicine, Burlington, VT, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Boyd
authors.affiliation: Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Natividad
authors.initials: N
authors.lastname: Stover
authors.affiliation: Department of Neurology, University of Colorado, School of Medicine, Aurora, CO, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Leehey
authors.affiliation: Department of Neurology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Zweig
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Nicholas
authors.affiliation: Departments of Neurology and Ophthalmology, Parkinson's Disease and Related Disorders Clinic, Center of Excellence, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bodis-Wollner
authors.affiliation: Department of Neurology, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Willis
authors.affiliation: University of Rochester, Center for Human Experimental Therapeutics, Rochester, NY, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.affiliation: Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Tilley
mesh_terms: D000368:Aged; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010300:Parkinson Disease / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D008996:Monoamine Oxidase Inhibitors
keywords: MAO-B inhibitor; Parkinson’s disease; disease modification; rasagiline; selegiline; treatment