Differential Temporal Dynamics and Motor-Non-Motor Dissociation After Inhaled Levodopa in Parkinson's Disease: A Post Hoc Analysis of the INLEVO-LIFE PD Study.
10 affiliations
- 1Department of Neurology, Complejo Hospitalario Universitario de A Coruña (CHUAC), 15006 A Coruña, Spain.
- 2Grupo de Investigación en Enfermedad de Parkinson y Otros Trastornos del Movimiento, INIBIC (Instituto de Investigación Biomédica de A Coruña), 15006 A Coruña, Spain.
- 3Hospital San Rafael, 15006 A Coruña, Spain.
- 4Fundación Degen, 15006 A Coruña, Spain.
- 5Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- 6Complejo Hospitalario de Cartagena, 30202 Murcia, Spain.
- 7Complejo Hospitalario Universitario de Ourense (CHUO), 32005 Ourense, Spain.
- 8Complejo Hospitalario Universitario de Pontevedra (CHOP), 36164 Pontevedra, Spain.
- 9Complejo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain.
- 10Hospital de Povisa, 36211 Vigo, Spain.
Abstract
Background/objectives
OFF episodes in Parkinson's disease (PD) include motor and non-motor manifestations, but their resolution after on-demand therapy may not be synchronous. We examined within-patient temporal dynamics of motor and non-motor responses after inhaled levodopa.Methods
This post hoc analysis used data from the prospective, multicenter, open-label INLEVO-LIFE PD study. At week 12, UPDRS-III and 10 OFF-related non-motor symptoms (NMSs) were assessed in OFF and 30, 60, and 90 min after inhaled levodopa. The principal post hoc outcome was the proportion of maximum early (30-60 min) benefit retained at 90 min for motor versus non-motor outcomes. Individual trajectories were also examined descriptively.Results
Thirty-four participants had complete serial assessments. Mean UPDRS-III scores were 25.91, 11.21, 12.00, and 16.00 at OFF, 30, 60, and 90 min, respectively (p < 0.0001); corresponding NMSS-OFF/ON total scores were 6.65, 2.09, 1.91, and 2.71 (p < 0.0001). Among 28 participants with early improvement in both outcomes, median benefit retained at 90 min was 67.1% for motor symptoms versus 100% for NMSs (p = 0.0011). Motor and non-motor improvement magnitudes were not significantly correlated at any time point. Individual trajectories showed marked interindividual heterogeneity in the timing and persistence of motor and non-motor responses.Conclusions
Motor and non-motor OFF manifestations improved rapidly after inhaled levodopa but showed partially dissociated temporal trajectories, challenging the assumption that OFF resolution is necessarily synchronous across symptom dimensions. Greater relative persistence of non-motor benefit at 90 min is hypothesis-generating and requires confirmation using validated NMF instruments and controlled designs.
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BibTeX
@article{garcia2026differential,
title = {{Differential Temporal Dynamics and Motor-Non-Motor Dissociation After Inhaled Levodopa in Parkinson's Disease: A Post Hoc Analysis of the INLEVO-LIFE PD Study.}},
author = {Diego Santos García and María Cerdán Sánchez and Rosa Yáñez Baña and Iria Cabo and Maria Icíar Cimas Hernando},
journal = {Medical sciences (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/medsci14060680},
url = {https://europepmc.org/article/MED/42930600},
note = {CC BY},
}
RIS
TY - JOUR
TI - Differential Temporal Dynamics and Motor-Non-Motor Dissociation After Inhaled Levodopa in Parkinson's Disease: A Post Hoc Analysis of the INLEVO-LIFE PD Study.
AU - Diego Santos García
AU - María Cerdán Sánchez
AU - Rosa Yáñez Baña
AU - Iria Cabo
AU - Maria Icíar Cimas Hernando
PY - 2026
DA - 2026/10/17
JO - Medical sciences (Basel, Switzerland)
DO - 10.3390/medsci14060680
UR - https://europepmc.org/article/MED/42930600
AB - Background/objectives OFF episodes in Parkinson's disease (PD) include motor and non-motor manifestations, but their resolution after on-demand therapy may not be synchronous. We examined within-patient temporal dynamics of motor and non-motor responses after inhaled levodopa.Methods This post hoc analysis used data from the prospective, multicenter, open-label INLEVO-LIFE PD study. At week 12, UPDRS-III and 10 OFF-related non-motor symptoms (NMSs) were assessed in OFF and 30, 60, and 90 min after inhaled levodopa. The principal post hoc outcome was the proportion of maximum early (30-60 min) benefit retained at 90 min for motor versus non-motor outcomes. Individual trajectories were also examined descriptively.Results Thirty-four participants had complete serial assessments. Mean UPDRS-III scores were 25.91, 11.21, 12.00, and 16.00 at OFF, 30, 60, and 90 min, respectively (p < 0.0001); corresponding NMSS-OFF/ON total scores were 6.65, 2.09, 1.91, and 2.71 (p < 0.0001). Among 28 participants with early improvement in both outcomes, median benefit retained at 90 min was 67.1% for motor symptoms versus 100% for NMSs (p = 0.0011). Motor and non-motor improvement magnitudes were not significantly correlated at any time point. Individual trajectories showed marked interindividual heterogeneity in the timing and persistence of motor and non-motor responses.Conclusions Motor and non-motor OFF manifestations improved rapidly after inhaled levodopa but showed partially dissociated temporal trajectories, challenging the assumption that OFF resolution is necessarily synchronous across symptom dimensions. Greater relative persistence of non-motor benefit at 90 min is hypothesis-generating and requires confirmation using validated NMF instruments and controlled designs.
SN - 2076-3271
ER -