title: Progression of Regional Microstructural Degeneration in Parkinson's Disease: A Multicenter Diffusion Tensor Imaging Study.
abstract: 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.
authors: Department of Veteran Affairs Medical Center, San Francisco, California, United States of America.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors: Yu
authors: http://orcid.org/0000-0001-8066-7275
authors: Y
authors: Zhang
authors: Department of Veteran Affairs Medical Center, San Francisco, California, United States of America.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors: I-Wei
authors: IW
authors: Wu
authors: Department of Veteran Affairs Medical Center, San Francisco, California, United States of America.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors: Duygu
authors: D
authors: Tosun
authors: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of America.
authors: Eric
authors: E
authors: Foster
authors: Department of Veteran Affairs Medical Center, San Francisco, California, United States of America.|Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors: Norbert
authors: N
authors: Schuff
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D056324:Diffusion Tensor Imaging / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000473:pathology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D011699:Putamen / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers