Objective: To study microstructural changes in grey and white matter in early drug-naïve Parkinson’s disease (PD) patients and correlate these changes with neuropsychological manifestations.

Background: De novo PD-patients with apathy, depression and anxiety show early and profound alteration in presynaptic serotoninergic function, besides nigro-striatal dopaminergic degeneration (1). These functional alterations may relate to early degeneration of serotoninergic terminals projecting from the raphe to limbic areas. Investigating long-range and microstructural changes in grey and white matter may help understand how apathy, depression and anxiety are related to serotoninergic dysfunction in PD-patients.

Methods: We conducted a case-control-control study enrolling 13 de novo PD-patients with apathy (Lille Apathy Rating Scale (LARS) scores ≥ -21), 14 de novo PD-patients without apathy and 15 age-matched healthy controls. Neuropsychological and neurological examination was performed to assess severity of motor and nonmotor symptoms using MDS-UPDRS-III, LARS, BDI-II and STAI-YB scales. All participants underwent anatomical and diffusion 1.5T MR imaging and Positron Emission Tomography (PET) imaging of presynaptic DA and 5-HT transporters using [11C]-PE2I and [11C]-DASB respectively. Fractional anisotropy (FA) and mean diffusivity (MD) were fitted using Diffusion Tensor modelling (DTI) for grey matter in limbic areas and for white matter in study-specific white matter tracts skeleton using TBSS. Microstructural metrics were compared using voxel-wise permutation-based statistics with GLM and between-groups ANCOVA adjusted for age and sex.

Results: Increased mean diffusivity correlated with greater severity of apathy in grey matter located in the anterior caudate nuclei, subgenual and dorsal anterior cingulate cortex bilaterally for PD-patients, as well as for depression. Moreover, decreased fractional anisotropy in ventral striatum, subgenual and dorsal anterior cingulate cortex and medial orbito-frontal cortex grey matter correlated with greater severity of apathy in PD-patients. Additionally, white matter FA changes indicated decreased directionality in the bilateral forceps minor, uncinate fasciculus, cingulum, anterior limb of the internal capsule and its radiations, and corpus callosum for greater severity of apathy.

Conclusions: Apathy in de novo PD-patients is related to microstructural changes in the limbic system, indicating increased disarray in grey and white matter overlapping with the functional alteration of serotoninergic terminals observed in PET.

References: 1. Maillet A, Krack P, Lhommée E, et al. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson’s disease. Brain. 2016;139(9):2486-2502.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microstructural-changes-in-white-and-grey-matter-related-to-apathy-depression-and-anxiety-in-de-novo-parkinsons-disease-patients/