Cortical thinning across Parkinson's disease stages and clinical correlates

Background: Imaging studies have revealed cortical thinning and subcortical atrophy occurring in Parkinson's disease (PD); however, the topographical distribution and clinical associations related to advancing stages of PD remains unclear. Objective: We aimed to investigate the topographical distribution of cortical and subcortical morphometric changes, and their clinical associations, related to increasing disease severity. Methods: In this cross-sectional imaging study, T1-weighted structural magnetic resonance imaging data for 80 non-demented PD patients and 30 age-matched healthy controls were analysed using FreeSurfer software suite to derive morphometric changes using whole-brain vertex-wise analysis, and surface-based (cortical) and volume-based (subcortical) parcellation maps. PD patients were divided into three groups of mild (n = 27), moderate (n = 27), and severe (n = 26) PD based disease duration and Hoehn and Yahr and Unified Parkinson's Disease Rating Scale Part-III motor severity scores. Results: Whole-brain vertex-wise analysis revealed cortical thinning in the orbitofrontal cortex in early PD (P =.011), and in the superior frontal (P =.002), caudal middle frontal gyrus (P =.001) and inferior parietal cortex (P =.006) in moderate PD. Severe PD patients showed additional cortical thinning in temporal and occipital cortices (P <.005). Subcortical volume loss was detected in the thalamus (P =.012) and hippocampus (P =.032) in moderate PD, which extended to the caudate (P =.012), putamen (P =.042) and amygdala (P =.008) in severe PD. Increasing disease duration and motor severity scores, correlated with cortical thinning in frontal, temporal, parietal and occipital cortices, and subcortical volumetric loss in the thalamus, caudate, putamen, amygdala and hippocampus. Lower global cognitive status, measured with MMSE, correlated with cortical thinning in temporal, parietal, frontal and cingulate cortices, and with volumetric loss in the hippocampus (r = 0.31; P =.009); suggesting subclinical pathogenic changes occur prior to the onset of cognitive impairment. Conclusion: In conclusion, in more severe disease stages PD patients exhibit progressive cortical thinning and subcortical volume loss which could have relevance to the development of cognitive impairment.