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Record W2948343640 · doi:10.1002/mds.27733

Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease

2019· article· en· W2948343640 on OpenAlexaff
Gennaro Pagano, Flavia Niccolini, Heather Wilson, Tayyabah Yousaf, Naheed L. Khan, Davide Martino, Christophe Plisson, Roger N. Gunn, Eugenii A. Rabiner, Paola Piccini, Thomas Foltynie, Marios Politis

Bibliographic record

VenueMovement Disorders · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPhosphodiesterase function and regulation
Canadian institutionsUniversity of Calgary
FundersMedical Research CouncilEuropean CommissionWellcome TrustKing's College LondonEli Lilly and CompanyNational Institute for Health and Care ResearchCHDI FoundationMichael J. Fox Foundation for Parkinson's Research
KeywordsPutamenDopamine transporterInternal medicineMedicineParkinson's diseaseEndocrinologyDopaminePhosphodiesteraseGastroenterologyDopaminergicDiseaseChemistryBiochemistryEnzyme

Abstract

fetched live from OpenAlex

ABSTRACT Background Recent work has shown loss of phosphodiesterase 10A levels in middle‐stage and advanced treated patients with PD, which was associated with motor symptom severity. Objectives To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden. Methods Seventy‐eight subjects were included in this study (17 early de novo, 15 early l ‐dopa–treated, 24 moderate‐advanced l ‐dopa–treated patients with PD, and 22 healthy controls). All participants underwent [ 11 C]IMA107 PET, [ 11 C]PE2I PET, and 3‐Tesla MRI scan. Results Early de novo PD patients showed loss of [ 11 C]IMA107 and of [ 11 C]PE2I binding in caudate and putamen ( P < 0.001); early l ‐dopa–treated PD patients showed additional loss of [ 11 C]IMA107 in the caudate ( P < 0.001; annual decline 3.6%) and putamen ( P < 0.001; annual decline 2.8%), but loss of [ 11 C]PE2I only in the putamen ( P < 0.001; annual decline 6.8%). Lower [ 11 C]IMA107 correlated with lower [ 11 C]PE2I in the caudate (rho = 0.51; P < 0.01) and putamen (rho = 0.53; P < 0.01). Longer disease duration correlated with lower [ 11 C]IMA107 in the caudate (rho = –0.72; P < 0.001) and putamen (rho = –0.48; P < 0.01), and with lower [ 11 C]PE2I only in the putamen (rho = –0.65; P < 0.001). Higher burden of motor symptoms correlated with lower [ 11 C]IMA107 in the caudate (rho = –0.42; P < 0.05) and putamen (rho = –0.41; P < 0.05), and with lower [ 11 C]PE2I only in the putamen (rho = –0.69; P < 0.001). Conclusion Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression. © 2019 International Parkinson and Movement Disorder Society

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.588

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.247
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations18
Published2019
Admission routes1
Has abstractyes

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