Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson’s disease

• DOI: 10.1007/s00259-025-07070-z
• Publication Date: 2025-01-31T07:49:26Z
• Authors: Jesús Silva-Rodrí...; Miguel Ángel Labr...; Sandra Castro-Lab...; Laura Muñoz-Delgado; Pablo Franco-Rosado; Ana María Castell...; Daniel Macías-García; Silvia Jesús; Astrid D. Adarmes...; Fátima Carrillo; Juan Francisco Ma...; David García-Solís; Florinda Roldán-Lora; Pablo Mir; Michel J. Grothe

Abstract

Purpose Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson’s disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD).

Methods 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [18F]FDG PET. We extracted grey matter volumes (sMRI), mean diffusivity (MD, dMRI), and standardized uptake value ratios ([18F]FDG PET) for 52 cortical regions included in a neuroanatomical atlas. We assessed group differences using ANCOVA models and further applied a cross-validated machine learning approach to identify the modality-specific brain regions that are most indicative of dementia status and assessed their diagnostic accuracy for group separation using receiver operating characteristic analyses.

Results In sMRI, atrophy of temporal and posterior-parietal areas allowed separating PDD from PD-CN (AUC = 0.77 ± 0.07), but diagnostic accuracy was poor for separating PD-MCI from PD-CN (0.57 ± 0.10). dMRI showed most pronounced diffusivity changes in the medial temporal lobe, which provided excellent diagnostic performance for PDD (AUC = 0.87 ± 0.06), and a more modest but still significant performance for PD-MCI (AUC = 0.71 ± 0.09). Finally, [18F]FDG PET revealed pronounced hypometabolism in posterior-occipital regions, which provided the highest diagnostic accuracies for both PDD (AUC = 0.89 ± 0.05) and PD-MCI (AUC = 0.78 ± 0.05). In statistical comparisons, both [18F]FDG PET (p < 0.001) and dMRI (p < 0.031) outperformed sMRI for detecting PDD and PD-MCI.

Conclusion Among the tested modalities, [18F]FDG PET was most accurate for detecting cortical changes associated with cognitive impairment in PD, especially at early stages. Diffusion measurements may represent a promising MRI-based alternative.