Objective: To investigate the longitudinal changes in striatal and extra-striatal dopaminergic and serotonergic innervation in apathetic and non-apathetic patients during the five years after the diagnosis of Parkinson’s disease (PD).

Background: PD patients may exhibit selective serotonergic pathology and microstructural disarray in the limbic system related to apathy, depression and anxiety at diagnosis, which represents distinctive pathological determinants early in the disease, although their progression is unknown.

Method: Fifteen apathetic (Lille Apathy Rating Scale (LARS) scores ≥ -21) and 15 non-apathetic PD patients were recruited at diagnosis in a longitudinal cohort study and performed in vivo PET imaging of the dopamine transporter (DAT) using [11C]-PE2I and the serotonin transporter (SERT) using [11C]-DASB at baseline and follow-up 3 to 5 years later. Group-based comparison of longitudinal changes was performed using linear mixed-effect models for clinical impairment and ROI-based analysis of dopaminergic and serotonergic presynaptic function.

Results: Apathy, depression and anxiety improved at follow-up in patients with apathy (n=11) in contrast to moderate increase in patients without apathy at diagnosis (n=11). Patients had similar progression of motor impairment, while mild impulsive behaviours developed in both groups. Nigro-striatal and pallidal presynaptic dopaminergic loss worsened over time in both groups (p<0.001). Remarkably, serotonergic innervation decreased in the putamen, caudate nucleus and pallidum in both groups (p<0.001), whereas serotonergic innervation increased in the ventral striatum and anterior cingular cortex selectively in apathetic patients, and in the posterior cingulate cortex in both groups (p=0.002), clustering in limbic versus extra-limbic longitudinal evolution patterns related to the severity of non-motor neuropsychiatric symptoms at diagnosis.

Conclusion: Patients with apathy, depression and anxiety at diagnosis exhibit distinctive limbic serotonergic innervation in the five years after diagnosis in comparison to non-apathetic PD patients, besides dissociated longitudinal evolution of serotonergic and dopaminergic dysfunction in the limbic system. This may suggest early compensatory changes in the serotonergic system within five years after diagnosis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dissociated-longitudinal-evolution-of-limbic-serotonergic-and-striatal-dopaminergic-and-serotonergic-pathology-in-apathetic-and-non-apathetic-patients-in-early-parkinsons-disease/