Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1

Robert A. Hauser, Ruosha Li, Adriana Pérez, Xuehan Ren, Dan Weintraub, Jordan Elm, John L. Goudreau, John Christopher Morgan, John Y. Fang, Michael J. Aminoff, Chadwick W. Christine, Rohit Dhall, Chizoba C. Umeh, James T. Boyd, Natividad Stover, Maureen Leehey, Richard M. Zweig, Anthony P. Nicholas, Ivan Bodis-Wollner, Allison WillisKarl Kieburtz, Barbara C. Tilley

Research output: Contribution to journalArticle

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Abstract

Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalJournal of Parkinson's Disease
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Monoamine Oxidase Inhibitors
Parkinson Disease
Activities of Daily Living
Neuroprotective Agents
England
Disease Progression
Linear Models
Observation
Outcome Assessment (Health Care)
Clinical Trials

Keywords

  • MAO-B inhibitor
  • Parkinson's disease
  • disease modification
  • rasagiline
  • selegiline
  • treatment

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease : An Analysis of NET-PD LS1. / Hauser, Robert A.; Li, Ruosha; Pérez, Adriana; Ren, Xuehan; Weintraub, Dan; Elm, Jordan; Goudreau, John L.; Morgan, John Christopher; Fang, John Y.; Aminoff, Michael J.; Christine, Chadwick W.; Dhall, Rohit; Umeh, Chizoba C.; Boyd, James T.; Stover, Natividad; Leehey, Maureen; Zweig, Richard M.; Nicholas, Anthony P.; Bodis-Wollner, Ivan; Willis, Allison; Kieburtz, Karl; Tilley, Barbara C.

In: Journal of Parkinson's Disease, Vol. 7, No. 1, 01.01.2017, p. 117-127.

Research output: Contribution to journalArticle

Hauser, RA, Li, R, Pérez, A, Ren, X, Weintraub, D, Elm, J, Goudreau, JL, Morgan, JC, Fang, JY, Aminoff, MJ, Christine, CW, Dhall, R, Umeh, CC, Boyd, JT, Stover, N, Leehey, M, Zweig, RM, Nicholas, AP, Bodis-Wollner, I, Willis, A, Kieburtz, K & Tilley, BC 2017, 'Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1', Journal of Parkinson's Disease, vol. 7, no. 1, pp. 117-127. https://doi.org/10.3233/JPD-160965
Hauser, Robert A. ; Li, Ruosha ; Pérez, Adriana ; Ren, Xuehan ; Weintraub, Dan ; Elm, Jordan ; Goudreau, John L. ; Morgan, John Christopher ; Fang, John Y. ; Aminoff, Michael J. ; Christine, Chadwick W. ; Dhall, Rohit ; Umeh, Chizoba C. ; Boyd, James T. ; Stover, Natividad ; Leehey, Maureen ; Zweig, Richard M. ; Nicholas, Anthony P. ; Bodis-Wollner, Ivan ; Willis, Allison ; Kieburtz, Karl ; Tilley, Barbara C. / Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease : An Analysis of NET-PD LS1. In: Journal of Parkinson's Disease. 2017 ; Vol. 7, No. 1. pp. 117-127.
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T1 - Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease

T2 - An Analysis of NET-PD LS1

AU - Hauser, Robert A.

AU - Li, Ruosha

AU - Pérez, Adriana

AU - Ren, Xuehan

AU - Weintraub, Dan

AU - Elm, Jordan

AU - Goudreau, John L.

AU - Morgan, John Christopher

AU - Fang, John Y.

AU - Aminoff, Michael J.

AU - Christine, Chadwick W.

AU - Dhall, Rohit

AU - Umeh, Chizoba C.

AU - Boyd, James T.

AU - Stover, Natividad

AU - Leehey, Maureen

AU - Zweig, Richard M.

AU - Nicholas, Anthony P.

AU - Bodis-Wollner, Ivan

AU - Willis, Allison

AU - Kieburtz, Karl

AU - Tilley, Barbara C.

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N2 - Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: 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.

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