Abstract Objectives This study investigated gray and white matter alterations and their association with motor and cognitive symptoms in early-stage Parkinson’s disease (PD). Methods Thirty-one early-stage PD patients and thirty matched healthy controls underwent multimodal MRI (VBM, DTI) and comprehensive clinical/neuropsychological assessments. We assessed gray matter atrophy, white matter microstructure, and caudate-cortical connectivity. Results PD patients showed selective deficits in memory (FCSRT total recall, p-FDR = 0.014) and processing speed (SDMT, p-FDR = 0.025). VBM revealed bilateral caudate atrophy (left, p-FDR = 0.024; right, p-FDR = 0.026). DTI demonstrated widespread microstructural alterations in corpus callosum and major association tracts. Disease duration negatively correlated with corpus callosum streamline counts (superior parietal p = 0.02; posterior parietal p = 0.004). UPDRS negatively correlated with FA in occipital (p = 0.002) and temporal (p = 0.0017) corpus callosum segments. Reduced caudate-cortical streamline density in frontal regions correlated with UPDRS/FCSRT scores; caudate-cingulum streamlines correlated with MMSE attention/calculation. Conclusions Our findings suggest early functionally relevant degeneration of fronto-caudate and interhemispheric pathways in PD. These structural changes correlate with specific cognitive and motor impairments, and are candidate imaging biomarkers for early PD progression and/or cognitive vulnerability. Advances in Knowledge This is the first tractography study to evaluate connectivity between the caudate nuclei and different frontal lobe regions, unveiling specific white matter alterations in early Parkinson’s disease. Our findings suggest that caudate atrophy, though not directly correlated with clinical variables, may underlie or result from impaired caudate-cortical connectivity, potentially accounting for some of the multifaceted PD symptoms
Bernabéu et al. (Sat,) studied this question.