Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Jost, Stefanie T.; Kaldenbach, Marie-Ann; Antonini, Angelo; Martinez‐Martín, Pablo; Timmermann, Lars; Odin, Per; Katzenschlager, Regina; Borgohain, Rupam; Fasano, Alfonso; Stocchi, Fabrizio; Kukkle, Prashanth Lingappa; Rodríguez-Violante, Mayela; Falup‐Pecurariu, Cristian; Schade, Sebastian; Petry‐Schmelzer, Jan Niklas; Metta, Vinod; Weintraub, Daniel; Deuschl, Günther; Espay, Alberto J.; Tan, Eng‐King; Bhidayasiri, Roongroj; Fung, Victor S.C.; Cardoso, Francisco; Trenkwalder, Claudia; Jenner, Peter; Dafsari, Haidar S.

doi:10.1002/mds.29410

Cited by 101 publications

(32 citation statements)

References 74 publications

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“…On the basis of previously published conversion methods, we report motor examination as UPDRS III scores to help interpret the data. The levodopa equivalent daily dose (LEDD) was calculated according to the method by Jost et al The total electrical energy delivered (TEED) was calculated using an established method by Koss et al, assuming a standard impedance of 1000Ω …”

Section: Methodsmentioning

confidence: 99%

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Jost,

Aloui,

Evans

et al. 2024

JAMA Netw Open

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ImportanceDeep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking.ObjectiveTo investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED).Design, Setting, and ParticipantsIn this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023.ExposureTreatment for PD of STN-DBS or MED.Main Outcomes and MeasuresAssessments included Parkinson’s Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale–motor examination, Scales for Outcomes in PD–activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed.ResultsThe study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, −10.9; 95% CI, −19.0 to −2.7; P = .01; ADL change: −2.0; 95% CI, −3.1 to −0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, −4.3; 95% CI, −13.2 to 4.7; P = .34; ADL change, −0.8; 95% CI, −2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, −2.0; 95% CI, −4.0 to −1.0; P = .003), mobility (−1.0; 95% CI, −2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (−821.4; 95% CI, −1111.9 to −530.8; P &lt; .001).Conclusions and RelevanceThis study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments.Trial RegistrationGerman ClinicalTrials Registry: DRKS00006735

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Section: Methodsmentioning

confidence: 99%

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Jost,

Aloui,

Evans

et al. 2024

JAMA Netw Open

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“…PD was diagnosed according to the clinical diagnostic criteria, 22 and HCs were age‐, gender‐ and education matched to patients. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS‐III) and Hoehn and Yahr (HY) scale were adopted to assess disease severity, and the levodopa ( l ‐dopa) and the dopamine agonist equivalent daily dosages were calculated for each patient 23 …”

Section: Methodsmentioning

confidence: 99%

“…The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) and Hoehn and Yahr (HY) scale were adopted to assess disease severity, and the levodopa (L-dopa) and the dopamine agonist equivalent daily dosages were calculated for each patient. 23 All subjects underwent a comprehensive neuropsychological battery (level II criteria of the MDS guidelines) as previously described, 24 specifically designed to target PD-cognitive deficits, which allow us to classify patients as PD-NC, PD-MCI, or PD with dementia (PDD) (for further details refer to the Supporting Information). The present study was approved by the Venice Research Ethics Committee, Venice, Italy.…”

Section: Participants and Clinical Assessmentmentioning

confidence: 99%

Brain Dynamics Complexity as a Signature of Cognitive Decline in Parkinson's Disease

Fiorenzato,

Moaveninejad,

Weis

et al. 2023

Movement Disorders

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BackgroundHiguchi's fractal dimension (FD) captures brain dynamics complexity and may be a promising method to analyze resting‐state functional magnetic resonance imaging (fMRI) data and detect the neuronal interaction complexity underlying Parkinson's disease (PD) cognitive decline.ObjectivesThe aim was to compare FD with a more established index of spontaneous neural activity, the fractional amplitude of low‐frequency fluctuations (fALFF), and identify through machine learning (ML) models which method could best distinguish across PD‐cognitive states, ranging from normal cognition (PD‐NC), mild cognitive impairment (PD‐MCI) to dementia (PDD). Finally, the aim was to explore correlations between fALFF and FD with clinical and cognitive PD features.MethodsAmong 118 PD patients age‐, sex‐, and education matched with 35 healthy controls, 52 were classified with PD‐NC, 46 with PD‐MCI, and 20 with PDD based on an extensive cognitive and clinical evaluation. fALFF and FD metrics were computed on rs‐fMRI data and used to train ML models.ResultsFD outperformed fALFF metrics in differentiating between PD‐cognitive states, reaching an overall accuracy of 78% (vs. 62%). PD showed increased neuronal dynamics complexity within the sensorimotor network, central executive network (CEN), and default mode network (DMN), paralleled by a reduction in spontaneous neuronal activity within the CEN and DMN, whose increased complexity was strongly linked to the presence of dementia. Further, we found that some DMN critical hubs correlated with worse cognitive performance and disease severity.ConclusionsOur study indicates that PD‐cognitive decline is characterized by an altered spontaneous neuronal activity and increased temporal complexity, involving the CEN and DMN, possibly reflecting an increased segregation of these networks. Therefore, we propose FD as a prognostic biomarker of PD‐cognitive decline. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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“…Parkinsonian medications include levodopa, dopamine agonists, monoamine oxidase B (MAOB) inhibitors, catechol‐O‐methyltransferase (COMT) inhibitors, and others. The total levodopa equivalent daily dose (LEDD) of each PD participant at V0 and V1 were calculated based on a common standard 23 . Although Kiainik et al 24 reported no effect of medication on CVR in PD, to minimize the potential bias of medication in our study, we assessed MRI in the practically defined off state (>12 hours after antiparkinsonian medication intake).…”

Section: Methodsmentioning

confidence: 99%

“…The total levodopa equivalent daily dose (LEDD) of each PD participant at V0 and V1 were calculated based on a common standard. 23 Although Kiainik et al 24 reported no effect of medication on CVR in PD, to minimize the potential bias of medication in our study, we assessed MRI in the practically defined off state (>12 hours after antiparkinsonian medication intake). Depressive symptoms were assessed using the 30-item Chinese version of the Geriatric Depression Scale (GDS).…”

Section: Participantsmentioning

confidence: 95%

Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study

Wang,

Li,

Jia

et al. 2023

Movement Disorders

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BackgroundThe change of microvascular function over the course of Parkinson's disease (PD) remains unclear.ObjectiveWe aimed to ascertain regional cerebrovascular reactivity (CVR) changes in the patients with PD at baseline (V0) and during a 2‐year follow‐up period (V1). We further investigated whether alterations in CVR were linked to cognitive decline and brain functional connectivity (FC).MethodsWe recruited 90 PD patients and 51 matched healthy controls (HCs). PD patients underwent clinical evaluations, neuropsychological assessments, and magnetic resonance (MR) scanning at V0 and V1, whereas HCs completed neuropsychological assessments and MR at baseline. The analysis included evaluating CVR and FC maps derived from resting‐state functional magnetic resonance imaging and investigating CVR measurement reproducibility.ResultsCompared with HCs, CVR reduction in left inferior occipital gyrus and right superior temporal cortex at V0 persisted at V1, with larger clusters. Longitudinal reduction in CVR of the left posterior cingulate cortex correlated with decline in Trail Making Test B performance within PD patients. Reproducibility validation further confirmed these findings. In addition, the results also showed that there was a tendency for FC to be weakened from posterior to anterior with the progression of the disease.ConclusionsMicrovascular dysfunction might be involved in disease progression, subsequently weaken brain FC, and partly contribute to executive function deficits in early PD. © 2023 International Parkinson and Movement Disorder Society.

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Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 101 publications

References 74 publications

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Brain Dynamics Complexity as a Signature of Cognitive Decline in Parkinson's Disease

Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study

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