Research Article| Volume 398, P31-38, March 15, 2019

Cortical thinning across Parkinson's disease stages and clinical correlates

  • Heather Wilson
    Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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  • Flavia Niccolini
    Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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  • Clelia Pellicano
    Department of Neuroscience, Mental Health and Secnsory Organs-(NESMOS), Sapienza University, Rome, Italy
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  • Marios Politis
    Corresponding author at: Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, 125 Coldharbour Lane, Camberwell, London SE5 9NU, UK.
    Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Published:January 17, 2019DOI:


      • Progressive cortical thinning and subcortical volumetric loss with increasing disease severity in PD.
      • Morphometric changes are associated with disease duration and motor symptom severity.
      • Morphometric changes are associated with lower MMSE scores.
      • Subclinical changes could contribute towards future development of cognitive decline.
      • Topographic patterns of cortical thinning could act as marker of disease severity and cognitive dysfunction.



      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.


      We aimed to investigate the topographical distribution of cortical and subcortical morphometric changes, and their clinical associations, related to increasing disease severity.


      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.


      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.


      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.



      H&Y (Hoehn and Yahr), MRI (magnetic resonance imaging), MMSE (Mini Mental State Examination), PD (Parkinson's disease), UPDRS (Unified Parkinson's Disease Rating Scale)
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