• Harry Costello, Yumeya Yamamori, Suzanne Reeves, Anette-Eleonore Schrag, Robert Howard, and Jonathan P Roiser.
• Institute of Cognitive Neuroscience, University College London, London, UK harry.costello@ucl.ac.uk.
• J. Neurol. Neurosurg. Psychiatr. 2023 Oct 1; 94 (10): 863870863-870.

BackgroundMotivational 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.MethodsLongitudinal 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.ResultsLinear 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)).ConclusionsOur 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.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

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