Objective: To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in parkinsonian patients with or without apathy, depression and anxiety

Background: De novo parkinsonian patients with apathy, depression and anxiety exhibit profound serotonergic dysfunction and microstructural disarray in the limbic system in comparison to non-apathetic patients, which supports distinct lesion profiles early in the disease although their progression is unknown.

Method: Fifteen apathetic (Lille Apathy Rating Scale (LARS) scores ≥ -21) and 15 non-apathetic parkinsonian patients were recruited at diagnosis and re-evaluated 3 to 5 years later in a two-group cohort study. In vivo PET imaging of the dopamine transporter (DAT) using [11C]-PE2I and the serotonin transporter (SERT) using [11C]-DASB was performed at baseline and repeated at follow-up. Longitudinal progression was assessed using linear mixed-effect models for clinical impairment and permutation-based inference for PET imaging.

Results: Eleven patients with apathy (PD-A) and 11 patients without apathy at diagnosis (PD-NA) completed the follow-up evaluation at median (IQR) 4.3 (0.6) years after diagnosis. Apathy, depression, anxiety and fatigue improved in PD-A patients over time, whereas these symptoms worsened in PD-NA patients (p<0.001). Besides neuropsychiatric symptoms, motor and other nonmotor (including somatic and sleep disorders) manifestations got worse as well as motor and nonmotor fluctuations in both groups. Striatal dopaminergic binding decreased bilaterally in both groups in the posterior and anterior putamen and caudate nucleus, and in the ventral tegmental area. Serotonin binding also decreased in both groups in the bilateral anterior putamen, medial thalamus, insula, right globus pallidus, left pulvinar, left subcallosal gyrus and bilateral dorsal raphe nucleus and ventral tegmental area, resulting in increased serotonin to dopamine transporters ratio in the posterior putamen bilaterally.

Conclusion: De novo parkinsonian patients with and without prominent apathy, depression and anxiety at diagnosis have distinct progression of neuropsychiatric burden over time and exhibit profound progression of striatal dopaminergic and limbic serotonergic dysfunction 3 to 5 years after diagnosis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progression-of-dopaminergic-and-serotonergic-dysfunction-related-to-motor-and-nonmotor-manifestations-in-apathetic-and-non-apathetic-parkinsonian-patients-a-4-year-longitudinal-double-tracer-pet-stud/