Progression of Regional Microstructural Degeneration in Parkinson's Disease: A Multicenter Diffusion Tensor Imaging Study

PLoS One. 2016 Oct 31;11(10):e0165540. doi: 10.1371/journal.pone.0165540. eCollection 2016.


This study aimed to identify the utility of diffusion tensor imaging (DTI) in measuring the regional distribution of abnormal microstructural progression in patients with Parkinson's disease who were enrolled in the Parkinson's progression marker initiative (PPMI). One hundred and twenty two de-novo PD patients (age = 60.5±9) and 50 healthy controls (age = 60.6±11) had DTI scans at baseline and 12.6±1 months later. Automated image processing included an intra-subject registration of all time points and an inter-subjects registration to a brain atlas. Annualized rates of DTI variations including fractional anisotropy (FA), radial (rD) and axial (aD) diffusivity were estimated in a total of 118 white matter and subcortical regions of interest. A mixed effects model framework was used to determine the degree to which DTI changes differed in PD relative to changes in healthy subjects. Significant DTI changes were also tested for correlations with changes in clinical measures, dopaminergic imaging and CSF biomarkers in PD patients. Compared to normal aging, PD was associated with higher rates of FA reduction, rD and aD increases predominantly in the substantia nigra, midbrain and thalamus. The highest rates of FA reduction involved the substantia nigra (3.6±1.4%/year from baseline, whereas the highest rates of increased diffusivity involved the thalamus (rD: 8.0±2.9%/year, aD: 4.0±1.5%/year). In PD patients, high DTI changes in the substantia nigra correlated with increasing dopaminergic deficits as well as with declining α-synuclein and total tau protein concentrations in cerebrospinal fluid. Increased DTI rates in the thalamus correlated with progressive decline in global cognition in PD. The results suggest that higher rates of regional microstructural degeneration are potential markers of PD progression.

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers / cerebrospinal fluid
  • Diffusion Tensor Imaging* / methods
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Neurodegenerative Diseases / diagnostic imaging*
  • Neurodegenerative Diseases / pathology*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • Phenotype
  • Putamen / metabolism
  • Putamen / pathology
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology


  • Biomarkers

Grant support

The study is initiated by PPMI study members that utilize PPMI data. PPMI is funded by the Michael J. Fox Foundation (MJFF) for Parkinson’s Research and other funding partners including a consortium of industry players, non-profit organizations and private individuals. Please visit PPMI website ( for details regarding the PPMI sponsors. The study is also supported in part by a MJFF grant (#9692). The MJFF has roles in study design and data collection but is not involved in data analysis, interpretation of data, writing of the paper, and decision to submit for publication. Other funding partners had no role in study design, data collection, data analysis, interpretation of data, writing of the paper, and decision to submit for publication.