Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease

Abstract

Background: In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data.

Methods: 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD.

Results: The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = - 0.265, η_p² = 0.070) and p = 0.001 (β = - 0.264, η_p² = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks.

Conclusions: We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

Keywords: DA, dopamine agonists; FSL, FMRIB's software library; LDE, levodopa dose equivalent; MDS-UPDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MMSE, Mini Mental State Examination; MNI, Montreal Neurological Institute; MRI, magnetic resonance imaging; Magnetic resonance imaging; Non-dopaminergic symptoms; PD, Parkinson's disease; Parkinson's disease/Parkinsonism; SCN, structural covariance network; SENS-PD, SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; Structural covariance network; TFCE, Threshold-Free Cluster Enhancement; VBM, voxel-based morphometry.

Fig. 1

Regional grey matter changes in PD patients. Red: Reduced grey matter in the posterior cingulate network related to cognitive impairment. Yellow: Reduced grey matter in the anterior cingulate network related to excessive daytime sleepiness. Images are overlaid on the most informative sagittal, coronal and transversal slices of the MNI (Montreal Neurological Institute) standard anatomical image (MNI coordinates are − 2, 18, 12). Results with a Threshold-free cluster enhancement (TFCE)-Family wise error (FWE) corrected p-value < 0.05 and a voxel size above 30 are shown. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Cingulate networks defined in healthy control subjects and in patients. Both cingulate networks defined in healthy control subjects and in patients with Parkinson's disease, overlaid on the most informative sagittal, coronal and transversal slices of the MNI (Montreal Neurological Institute) standard anatomical image (MNI coordinates are 8, − 14, 20). A: Posterior cingulate network. B: Anterior cingulate network.