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Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia

BACKGROUND: Motivational symptoms such as apathy and anhedonia are common in Parkinson’s disease (PD), respond poorly to treatment, and are hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in PD but the association h...

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Autores principales: Costello, Harry, Yamamori, Yumeya, Reeves, Suzanne, Schrag, Anette-Eleonore, Howard, Robert, Roiser, Jonathan P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511995/
https://www.ncbi.nlm.nih.gov/pubmed/37221053
http://dx.doi.org/10.1136/jnnp-2022-330790
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author Costello, Harry
Yamamori, Yumeya
Reeves, Suzanne
Schrag, Anette-Eleonore
Howard, Robert
Roiser, Jonathan P
author_facet Costello, Harry
Yamamori, Yumeya
Reeves, Suzanne
Schrag, Anette-Eleonore
Howard, Robert
Roiser, Jonathan P
author_sort Costello, Harry
collection PubMed
description BACKGROUND: Motivational symptoms such as apathy and anhedonia are common in Parkinson’s disease (PD), respond poorly to treatment, and are hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in PD but the association has never been examined longitudinally. We investigated whether progression of dopaminergic dysfunction was associated with emergent apathy and anhedonia symptoms in PD. METHODS: Longitudinal cohort study of 412 newly diagnosed patients with PD followed over 5 years as part of the Parkinson’s Progression Markers Initiative cohort. Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item Geriatric Depression Scale (GDS-15) and part I of the MDS-Unified Parkinson’s Disease Rating Scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter (DAT) imaging. RESULTS: Linear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio (SBR) and apathy/anhedonia symptoms, which emerged as PD progressed (interaction:β=−0.09, 95% CI (−0.15 to -0.03), p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average 2 years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β=−0.06, 95% CI (−0.13 to 0.01)) or motor symptoms (β=0.20, 95% CI (−0.25 to 0.65)). CONCLUSIONS: Our findings support a central role for dopaminergic dysfunction in motivational symptoms in PD. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies.
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spelling pubmed-105119952023-09-22 Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia Costello, Harry Yamamori, Yumeya Reeves, Suzanne Schrag, Anette-Eleonore Howard, Robert Roiser, Jonathan P J Neurol Neurosurg Psychiatry Neuropsychiatry BACKGROUND: Motivational symptoms such as apathy and anhedonia are common in Parkinson’s disease (PD), respond poorly to treatment, and are hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in PD but the association has never been examined longitudinally. We investigated whether progression of dopaminergic dysfunction was associated with emergent apathy and anhedonia symptoms in PD. METHODS: Longitudinal cohort study of 412 newly diagnosed patients with PD followed over 5 years as part of the Parkinson’s Progression Markers Initiative cohort. Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item Geriatric Depression Scale (GDS-15) and part I of the MDS-Unified Parkinson’s Disease Rating Scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter (DAT) imaging. RESULTS: Linear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio (SBR) and apathy/anhedonia symptoms, which emerged as PD progressed (interaction:β=−0.09, 95% CI (−0.15 to -0.03), p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average 2 years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β=−0.06, 95% CI (−0.13 to 0.01)) or motor symptoms (β=0.20, 95% CI (−0.25 to 0.65)). CONCLUSIONS: Our findings support a central role for dopaminergic dysfunction in motivational symptoms in PD. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies. BMJ Publishing Group 2023-10 2023-05-23 /pmc/articles/PMC10511995/ /pubmed/37221053 http://dx.doi.org/10.1136/jnnp-2022-330790 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Neuropsychiatry
Costello, Harry
Yamamori, Yumeya
Reeves, Suzanne
Schrag, Anette-Eleonore
Howard, Robert
Roiser, Jonathan P
Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title_full Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title_fullStr Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title_full_unstemmed Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title_short Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: associations with apathy and anhedonia
title_sort longitudinal decline in striatal dopamine transporter binding in parkinson’s disease: associations with apathy and anhedonia
topic Neuropsychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511995/
https://www.ncbi.nlm.nih.gov/pubmed/37221053
http://dx.doi.org/10.1136/jnnp-2022-330790
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