Objective: Explore relationships of frontostriatal (FS) and posterior cortical (PC) cognitive performance with gray matter (GM) microstructural integrity in Parkinson’s disease (PD).

Background: The dual syndrome hypothesis distinguishes two cognitive subtypes in PD: the FS subtype is characterized by attention/working memory and executive deficits, while the PC subtype is characterized by visuospatial, memory and language deficits. However, studies investigating GM integrity in relation to cognitive performance in PD primarily employed macrostructural techniques (e.g., cortical thickness), reporting inconsistent findings. Measures of GM microstructural integrity may be more sensitive to alterations associated with FS and PC cognitive performance.

Method: 18 participants with PD (mean age: 67.0±7.3; 44% female) completed neuropsychological testing of FS and PC cognitive domains, and a 3T MRI scan including a multi-shell diffusion-weighted sequence. Raw scores on tests were mean-centered and averaged to create FS and PC composite scores. GM microstructural metrics were computed using neurite orientation dispersion and density imaging: (a) Neurite Density Index (NDI), reflecting density of axons and dendrites, (b) Orientation Dispersion Index (ODI), reflecting dendritic arborization complexity, and (c) isometric Volume fraction (isoVf), reflecting free water. Voxel-wise regression models were constructed to examine the relationships of FS and PC scores with NDI, ODI and isoVf (voxel-level uncorrected p<.01; cluster-level uncorrected p<.05), controlling for age, sex and educational level.

Results: FS score was positively associated with NDI and ODI in bilateral superior medial, middle and inferior frontal gyri, and right superior temporal gyrus. PC score was positively associated with NDI and ODI in right superior temporal gyrus, left cuneus, bilateral posterior cingulate cortices, right supramarginal gyrus, and bilateral superior medial frontal gyri and negatively associated with isoVf in left superior medial frontal gyrus, right thalamus, bilateral caudate and accumbens nuclei.

Conclusion: Although lower neurite density and dendritic arborization complexity was associated with lower FS performance primarily in frontal regions and PC performance primarily in posterior cortical regions, clusters were also found outside of the anatomical regions designated by each subtype’s label.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gray-matter-microstructural-integrity-in-relation-to-frontostriatal-and-posterior-cortical-cognitive-performance-in-parkinsons-disease/