Cortical thinning pattern according to differential nigrosome involvement in patients with Parkinson's disease

The pathological hallmark of Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, where the dopaminergic neurons form five clusters called nigrosomes 1–5 (N1–N5). N1 is the largest and considered to be the most affected by PD, followed by N2, N4, N3, and N5. Recently, an MRI study suggested a sequential progression of loss from N1 to N4. As the extent of cortical thinning widens as PD progresses, we aimed to define cortical thinning patterns according to the differential involvement of N1 and N4 in PD patients. Cortical thickness was analyzed in 83 PD patients (29 with N1 loss on at least one side of the brain, but no N4 loss; and 54 with N4 loss on at least one side) and 35 healthy subjects with age, sex, disease duration, and intracranial volume as covariates. On patient-wise analysis, for areas with more cortical thinning than the controls, PD patients with N4 loss had wider cortical thinning involving more dorsolateral prefrontal cortex and temporal areas than PD patients with only N1 loss, but cortical thinning did not significantly differ between these two patient groups. However, cortical thinning was more apparent in hemisphere-level analysis with statistically significant clusters being found more in hemispheres with N4 loss than hemispheres with N1 loss in PD patients compared to normal hemispheres of the controls. Cortical thinning occurred in a similar propagation pattern to that seen with PD progression, supporting past hypotheses on the sequential progression of nigrosome loss from N1 to N4.