Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment

Abstract

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort.

Materials and methods: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer.

Results: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm² cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions.

Conclusion: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.

Keywords: Parkinson’s Disease-Cognitive Rating Scale; Parkinson’s disease; cortical thickness; cortical volume; magnetic resonance imaging; mild cognitive impairment; neuroimaging.

Figure 1

Participant flowchart for the MRI study: attrition and exclusion metrics.

Figure 2

Vertex-wise analysis of cortical volume differences between PD-IC and PD-MCI groups. This figure presents a statistical parametric map illustrating regions of significant cortical volume (CVol) differences between Parkinson’s disease patients with intact cognition (PD-IC, n = 37) and those with mild cognitive impairment (PD-MCI, n = 14). The results are projected onto a standardized cortical surface template. The color scale represents the statistical significance of group differences, expressed as −log10(p-value), where warmer colors indicate greater statistical significance. This visualization allows for the spatial localization of cortical regions most affected by cognitive status in Parkinson’s disease. PD-IC, Parkinson’s disease with intact cognition; PD-MCI, Parkinson’s disease with mild cognitive impairment; CVol, cortical volume.

Figure 3

Cortical regions exhibiting significant associations with PD-CRS scores across multiple domains in Parkinson’s disease cohort. Subpanels: The top subpanel illustrates areas correlated with the PD-CRS total score, the middle with Sustained Attention, and the bottom with Clock Drawing Test scores. Statistical significance was determined using permutation-based testing with 1,000 iterations at a threshold of p < 0.05. The color scale represents the strength of the correlation, expressed as −log10(p-value), where warmer colors indicate stronger associations.

Figure 4

Cortical thickness areas showed significant correlations with PD-CRS semantic verbal fluency (upper panel), alternated verbal fluency (between letter S and clothing items, in the middle panel), and Frontal-Subcortical Score (lower panel) in a sample of non-demented PD patients. Color scale indicates correlation strength [−log10(p-value)]. Significance determined by permutation testing (1,000 iterations, p < 0.05).