A key neuropathological substrate of Parkinson's disease is the loss of dopaminergic neurons in the substantia nigra pars-compacta (SNpc). Neuromelanin-sensitive MRI techniques have been developed to visualize the SNpc in vivo. Previous studies have consistently shown reduced volume and/or signal intensity in the SNpc in PD patients, a finding correlated with the severity of motor symptoms. However, the relationship between this marker of nigral degeneration and cognitive performance in PD remains poorly characterized.

Objective: To investigate the association between SNpc contrast-ratio and cognitive function in a cohort of Mexican Parkinson's disease patients and healthy controls.

Methods: Cognitive performance was assessed in 92 patients and 27 controls using the Montreal Cognitive Assessment (MoCA). All participants underwent MRI on a 3T scanner. The acquisition protocol included high-resolution T1-weighted sequences alongside neuromelanin‑weighted imaging. The SNpc was coregistered to MNI space and segmented using an atlas of subcortical nuclei. SNpc contrast-ratio was estimated using the Red Nucleus as a reference region. A general linear model was used to assess SNpc contrast-ratio as a predictor of MoCA scores, with status (PD vs HC), age, sex. education, and disease duration as covariates.

Results: PD patients showed a reduced SNpc contrast-ratio (p=0.03). Women showed a higher contrast-ratio (p=0.001). PD patients (p=0.01), but not HC (p=0.5), showed a significant association between SNpc contrast-ratio and MoCA scores. However, the interaction between SNpc contrast-ratio and status didn’t show a significant association (p=0.4), suggesting the effect is stronger and more consistent in PD patients but not significantly different from the effect in HC.

The connectivity of the substantia nigra with motor and associative brain areas is well established. Previous investigations have found little evidence linking SNpc contrast-ratio to cognitive performance. Our analysis revealed a modest but significant effect of SNpc contrast-ratio on cognition. This finding provides evidence linking a neuropathological hallmark of Parkinson's disease with one of its most prevalent and disabling non-motor symptoms.