Objective: To investigate whether alterations of cortical thickness correspond to cognitive dysfunction in XDP patients.

Background: X-linked dystonia-parkinsonism (XDP) is a severe, hereditary movement disorder characterized by a combination of adult-onset dystonia and subsequent parkinsonism. Aside from motor manifestations, executive and other cognitive functions are impaired in XDP (1). Prior studies have shown extensive striatal neurodegeneration and mildly reduced cortical thickness in the frontal and temporal cortex (2).

Methods: MRI scans were acquired in 17 male XDP patients from the Philippines (40.1±7.5 years) and 17 ethnicially matched male controls (35.2±7.4 years). ROI-labeled cortical thickness was calculated after auto-segmentation of preprocessed T1-weighted images via the Mindboggle software as a cross-platform Docker container (3). ROIs were defined using a modified Desikan-Killiany-Tourville labelling protocol. A priori defined ROIs for the DLPFC, pre-SMA, ACC, anterior insular cortex (AIC), inferior frontal junction (IFJ), premotor cortex (PMC), and posterior parietal cortex (PPC) were analyzed. The cuneus has been chosen as a control ROI as this region is not involved in cognitive functions. Clinical assessment of cognitive domains was performed by trained healthcare professionals using MoCA, MMSE, and Frontal Assessment Battery (FAB).

Results: There were significant group differences for the DLPFC (-3.64%; p=.022), pre-SMA (-4.17%; p=.033), AIC (-3.46%; p=.013), IFJ (-5.04%; p=.013), and PMC (-5.82%; p=.010). All of them were significantly correlated with the MMSE (DLPFC: r=.597, p=.031; pre-SMA: r=.604, p=.029; AIC: r=.824, p<.001; IFJ: r=.755, p<.001; PMC: r=.778, p=.002). In addition, the PMC and IFJ correlated with the MoCA (r=.596, p=.032 and r=.496, p=.043) and the IFJ with the FAB (r=.554, p=.026). Cortical thickness of PPC and cuneus was not reduced in patients. None of the cognitive tests correlated with cortical thickness of the PPC and cuneus.

Conclusions: Cortical thinning is present in the frontal cortex of XDP patients but mild in comparison to the remarkable striatal decline. Cognitive assessments correlated with the degree of cortical thickness in the patients. Although cortical alterations are most likely a secondary effect of striatal neurodegeneration, we were able to demonstrate the potential use of preselected ROIs as a neuroimaging marker for cognitive decline in XDP.

References: (1) Howe, L. L., Kellison, I. L., Fernandez, H. H., Okun, M. S., & Bowers, D. (2009). Neuropsychological Profile of a Filipino Gentleman with X-Linked Dystonia–Parkinsonism: A Case Report of Lubag Disease. The Clinical Neuropsychologist, 23(1), 100-117. (2) Brüggemann, Norbert, et al. “Neuroanatomical changes extend beyond striatal atrophy in X-linked dystonia parkinsonism.” Parkinsonism & related disorders 31 (2016): 91-97. (3) Klein, Arno, and Joy Hirsch. “Mindboggle: a scatterbrained approach to automate brain labeling.” NeuroImage 24.2 (2005): 261-280.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-thinning-as-a-neuroimaging-marker-of-cognitive-decline-in-x-linked-dystonia-parkinsonism/