Cortical and subcortical gray matter (GM) atrophy may progress differently during the course of Parkinson's disease (PD). We delineated and compared the longitudinal pattern of these PD-related changes. Structural MRIs and clinical measures were obtained from 76 PD with different disease durations and 70 Controls at baseline, 18-, and 36 months. Both cortical and subcortical (putamen, caudate, and globus pallidus) GM volumes were obtained, compared, and associated with PD clinical measures at baseline. Their volumes and rates of change also were compared among Controls, PDs, and PD subgroups based on duration of illness [≤1 year (PD(E)), 1-5 years (PD(M)), and >5 years (PD(L))]. Compared to Controls, PD subjects displayed smaller cortical GM and striatal(putamen, caudate, ps ≤0.001), volumes at baseline. Cortical GM volumes were negatively associated with disease duration at baseline, whereas striatal volumes were not. PD subjects demonstrated accelerated volume loss in cortical GM (p = 0.006), putamen (p = 0.034), and caudate (p = 0.008) compared to Controls. Subgroup analyses demonstrated that accelerated cortical atrophy reached statistical significance in PD subjects with duration of illness 1-5 years (PD(M), ps<0.001) and the trend of accelerated atrophy seemed to persist until later stages, whereas striatal atrophy occurred in PD subjects with PD(E) (p = 0.021 for putamen, p = 0.005 for caudate) and PD(M) (p = 0.002 for putamen, p = 0.001 for caudate) that significantly slowed down in PD(L) (ps for PD(L) vs PD(E) or PD(M): <0.01). The pattern of GM loss in PD differs in cortical and subcortical regions, with striatal atrophy occurring earlier and extra-striatal cortical atrophy later.

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