Objective: To investigate patterns of cortical thickness that are associated with disease severity and response to levodopa.

Background: Cortex affection is a neuropathological correlate of advanced disease stages [1] in Parkinson’s disease (PD) and a recent meta-analysis found, that higher doses of levodopa were associated with lower cortical thickness in the medial prefrontal cortex and the anterior cingulate cortex [2]. As higher levodopa doses may be prescribed, if response is unsatisfactory, we hypothesized, that changes in cortical thickness of this area may also be associated with response to levodopa and the general motor impairment.

Method: We included a total of 118 patients with PD (38 female), who presented to our movement disorder clinic and received a standardized motor assessment with the Unified Parkinson’s Disease Rating Scale (UPDRS) [3] after cessation of dopaminergic medication for at least 12 hours (medOFF) and after administration of 200 mg of soluble levodopa (medON). The motor response to levodopa was calculated as the relative change in UPRDS compared to the medOFF baseline. Additionally, we acquired high-resolution T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. The Computational Anatomy Toolbox was used for preprocessing. After segmentation and normalization, measures of cortical thickness were obtained from the preprocessed data. Data were analyzed using a multiple regression with subject age, sex, scanner type, and total intracranial volume as covariates. Voxel clusters were regarded as significant for a family-wise error corrected p_FWE-value of 0.05 at a height threshold of p < 0.005. We chose k = 100 voxels as a threshold for contiguous voxels.

Results: In our cohort, mean UPDRS value in medOFF condition was 37.03 ± 11.19 points and mean medON value was 20.09 ± 8.59 points; the average improvement was 46.16 ± 16 %.
Higher cortical thickness of a cluster in the left middle cingulum, extending into the medial frontal gyrus, was associated with better response to Levodopa. Additionally, we report a significant association between UPDRS values in medOFF condition and lower cortical thickness in a voxel cluster peaking in the left middle cingulum.

Conclusion: We confirm our hypothesis, that response to levodopa is associated with a preserved cortical thickness in the dorsomedial prefrontal cortex. Our results may help to elucidate neurobiological factors that contribute to treatment success in advanced PD.

References: [1] H. Braak, K.D. Tredici, U. Rüb, R.A.I. de Vos, E.N.H. Jansen Steur, E. Braak, Staging of brain pathology related to sporadic Parkinson’s disease, Neurobiology of Aging. 24 (2003) 197–211. https://doi.org/10.1016/S0197-4580(02)00065-9. [2] L. Sheng, P. Zhao, H. Ma, J. Radua, Z. Yi, Y. Shi, J. Zhong, Z. Dai, P. Pan, Cortical thickness in Parkinson’s disease: a coordinate-based meta-analysis, Aging (Albany NY). 13 (2021) 4007–4023. https://doi.org/10.18632/aging.202368. [3] The Unified Parkinson’s Disease Rating Scale (UPDRS): Status and recommendations, Movement Disorders. 18 (2003) 738–750. https://doi.org/10.1002/mds.10473.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/patterns-of-cortical-thinning-in-patients-with-parkinsons-disease/