Objective: To compare the response of motor and non-motor symptoms (NMS) to a L-dopa challenge test  between late stage (LS) PD patients and advanced stage (AD) PD patients.

Background: L-dopa efficacy on PD cardinal motor symptoms may decrease with disease progression. If so, a simplification of drug therapy regimen in later disease stages may be beneficial.

Method: A case-control study on 17 LSPD patients (Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 in MED ON) and 17 advanced (AD) PD (presence of L-dopa induced motor complications) patients matched for age at disease onset underwent an acute levodopa challenge test and a cross-sectional clinical assessment for motor, NMS, namely blood pressione (BP), pain and fatigue, and quality of life (QoL).

Results: Demographic and clinical data of patients are detailed in Table 1. Fourteen LSPD patients (82%) had fulfil the criteria for probable PDD (MDS Task Force criteria). After L-dopa intake improved 14% the MDS-UPDRS-III score (p<0.001) of LSPD patients, including improvement of gait and freezing of gait (FOG) (p<0.05) but no other axial signs, but had and no effect on NMS, except for a lowering of orthostatic BP. Conversely, the MDS-UPDRS-III score of ADPD patients improved 51% (p<0.001) with L-dopa, including most axial signs. L-dopa improved fatigue and pain of ADPD patients, despite worsening, orthostatic BP (Table 1). In LSPD, ∆MDS-UPDRS-III had a positive correlation with MDS-UPDRS-IV, item 4.2 and ∆AIMS (R=0.536/0.730/0.535), while no significant  correlations wereare found for ADPD patients. Multiple regression analysis showed that PDD was the only variable that independently predicted  a worse L-dopa response (β=-14.4; p=0.011; R2:0.691).

Conclusion: The L-dopa response on motor and non-motor symptoms is worse in LSPD patients compared to ADPD patients, despite similar age, age at PD onset and disease duration. Dementia is highly predictive of a worse a response to L-dopa, probably reflecting more disease progression. Identification of clinical markers of better or worse L-dopa responsiveness could help clinicians in the challenging treatment management of these patients and in the education of patients and families.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-response-in-later-stages-of-parkinsons-disease-a-case-control-study/