Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes

Abstract

Background Parkinson’s disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Methods Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 Tesla high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. Results No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p=0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p=0.06). Conclusion While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes.

Alterations of putaminal shape in de novo Parkinson's disease

“…Damage of the nucleus accumbens has also been reported in PD patients. Atrophy of this structure has been associated with cognitive impairment and chronic dopaminergic treatment . Our patients were not only drug‐naïve, but also did not show any sign of cognitive impairment, which could explain the lack of detected differences in the accumbens.…”

“…Very recently, several studies have applied shape analysis to patients with PD, but results are inconsistent. Of these, only one study targeted drug‐naïve patients, whereas the others dealt with patients undergoing medications, either cognitively normal or showing cognitive deficits or apathy …”

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease

“…These results are consistent with the idea that in the PD-like brain state, where striatal regions are dopamine-deafferented, motor improvement afforded by dopamine agonists are acting on upregulated postsynaptic dopamine receptors to rapidly provide more normal function of striatal outflow to downstream motor structures. The limbic brain regions involved in ICDs are largely intact in PD [39] (but see [40,41]) and in rats with 6OHDA-induced lesions of the DLS [10,13], and Dopamine agonist therapy for PD may serve to over activate limbic dopamine receptors. Furthermore, chronic exposure to PPX upregulates D3R [42].…”

Striatal and Hippocampal Atrophy in Idiopathic Parkinson’s Disease Patients without Dementia: A Morphometric Analysis

“…An additional limitation of previous studies is that while atrophy of the hippocampus and related medial temporal lobe cortex are reported as common features in PD (7, 8, 19, 20), morphometric studies have either not addressed (11, 13, 16, 17) or found (3, 12, 14, 15, 18, 21) hippocampal shape differences.…”