Objective: To characterize cortical microstructural alterations in multiple system atrophy (MSA) and to examine their associations with clinical features and neuropsychological performance.

Background: Cortical mean diffusivity (cMD) is a surface-based diffusion magnetic resonance imaging (MRI) approach capable of detecting microstructural abnormalities and neuronal loss across various neurodegenerative diseases.^1–3 Although diffusion MRI has proven useful for characterizing microstructural abnormalities in white and subcortical gray matter in MSA,⁴ cortical microstructural alterations remain largely underexplored in this disease.

Method: A sample of 29 patients with MSA and 35 healthy controls (HCs) underwent clinical, neuropsychological, and multimodal MRI evaluation. T1-weighted and diffusion-weighted imaging sequences were used to calculate cMD as a measure of cortical microstructural abnormalities. Group differences were assessed using two-class comparisons, and Cohen’s d effect size was computed. Age-adjusted partial correlations were conducted to examine associations between cMD and clinical or neuropsychological measures. Statistical significance was set at p<0.05 with FDR correction.

Results: Patients with MSA showed significantly increased cMD in bilateral rostral regions, predominantly involving frontal and temporal areas with both lateral and medial extension, compared with HCs [figure2]. Moreover, patients with MSA exhibited higher apathy, depression, non-motor symptom burden, and neuropsychiatric disturbances [table1], together with lower performance across all cognitive domains and global cognition Z score [figure1]. After FDR correction, higher cMD in an extended anteromedial cluster with its peak in the right medial orbitofrontal cortex correlated with lower global cognition Z score in patients with MSA [figure3].

Conclusion: These results evidenced a bilateral predominantly fronto-temporal pattern of cortical microstructural degeneration that relates to global cognitive decline in patients with MSA. cMD emerges as a promising diffusion-based biomarker of cortical involvement in MSA, with potential utility for clinical characterization.

Table 1

Figure 1

Figure 2

Figure 3

References: 1. Montal V, Vilaplana E, Alcolea D, Pegueroles J, Pasternak O, González-Ortiz S, et al. Cortical microstructural changes along the Alzheimer’s disease continuum. Alzheimer’s and Dementia. 2018;14(3):340–51. doi:10.1016/j.jalz.2017.09.013 PubMed PMID: 29080407.
2. Illán-Gala I, Montal V, Pegueroles J, Vilaplana E, Alcolea D, Dols-Icardo O, et al. Cortical microstructure in the amyotrophic lateral sclerosis-frontotemporal dementia continuum. Neurology. 2020;95(18):E2565–76. doi:10.1212/WNL.0000000000010727 PubMed PMID: 32913016.
3. Pardo J, Montal V, Campabadal A, Oltra J, Uribe C, Roura I, et al. Cortical Macro- and Microstructural Changes in Parkinson’s Disease with Probable Rapid Eye Movement Sleep Behavior Disorder. Movement Disorders. 2024;39(5):814–24. doi:10.1002/mds.29761 PubMed PMID: 38456361.
4. Pasquini J, Firbank MJ, Ceravolo R, Silani V, Pavese N. Diffusion Magnetic Resonance Imaging Microstructural Abnormalities in Multiple System Atrophy: A Comprehensive Review. Movement Disorders. John Wiley and Sons Inc; 2022. p. 1963–84. doi:10.1002/mds.29195 PubMed PMID: 36036378.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-mean-diffusivity-as-a-measure-of-microstructural-neurodegeneration-in-multiple-system-atrophy/