This study investigates the longitudinal relationship between magnetic susceptibility and clinical severity in Parkinson's disease (PD). Using quantitative susceptibility mapping (QSM), the researchers found that increased baseline magnetic susceptibility in specific brain regions, such as the right temporal cortex, nucleus basalis of Meynert, and putamen, was associated with greater cognitive severity after 3 years. Similarly, increased susceptibility in the basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was linked to greater motor severity. Follow-up susceptibility in these regions was also associated with increased cognitive and motor severity, with additional involvement of the hippocampus related to cognitive severity. However, no consistent increases in susceptibility were observed over the 3-year period. The study highlights that QSM may predict cognitive decline in PD months before it becomes apparent. However, the results suggest that QSM does not show consistent longitudinal changes over the study period. The researchers propose that additional tissue metrics may be needed alongside QSM to monitor PD progression in clinical practice and therapeutic trials. The study also found that susceptibility changes in certain brain regions, such as the orbitofrontal cortex and hippocampus, were related to poorer cognitive and motor outcomes. The findings suggest that susceptibility may be influenced by both paramagnetic and diamagnetic sources, and that the relationship between susceptibility and clinical severity may be more complex than previously thought. The study also notes that susceptibility changes may be affected by factors such as myelin content and pathological protein accumulation. The results suggest that future research should combine imaging modalities sensitive to myelin and pathological protein accumulation to better understand how these factors relate to tissue composition changes and clinical severity in PD.This study investigates the longitudinal relationship between magnetic susceptibility and clinical severity in Parkinson's disease (PD). Using quantitative susceptibility mapping (QSM), the researchers found that increased baseline magnetic susceptibility in specific brain regions, such as the right temporal cortex, nucleus basalis of Meynert, and putamen, was associated with greater cognitive severity after 3 years. Similarly, increased susceptibility in the basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was linked to greater motor severity. Follow-up susceptibility in these regions was also associated with increased cognitive and motor severity, with additional involvement of the hippocampus related to cognitive severity. However, no consistent increases in susceptibility were observed over the 3-year period. The study highlights that QSM may predict cognitive decline in PD months before it becomes apparent. However, the results suggest that QSM does not show consistent longitudinal changes over the study period. The researchers propose that additional tissue metrics may be needed alongside QSM to monitor PD progression in clinical practice and therapeutic trials. The study also found that susceptibility changes in certain brain regions, such as the orbitofrontal cortex and hippocampus, were related to poorer cognitive and motor outcomes. The findings suggest that susceptibility may be influenced by both paramagnetic and diamagnetic sources, and that the relationship between susceptibility and clinical severity may be more complex than previously thought. The study also notes that susceptibility changes may be affected by factors such as myelin content and pathological protein accumulation. The results suggest that future research should combine imaging modalities sensitive to myelin and pathological protein accumulation to better understand how these factors relate to tissue composition changes and clinical severity in PD.