Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease

Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.

We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems.

De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long-range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right-sided limbic subnetwork involving limbic and frontal association tracts.

Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.