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

• Published in: PloS one 2016-10, Vol.11 (10), p.e0165540-e0165540
• Main Authors: Zhang, Yu, Wu, I-Wei, Tosun, Duygu, Foster, Eric, Schuff, Norbert
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Alzheimers disease; Anisotropy; Bioindicators; Biology and Life Sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Brain; Cerebrospinal fluid; Cognition; Cognitive ability; Correlation analysis; Degeneration; Dementia; Diagnostic imaging; Diffusion; Diffusion Tensor Imaging - methods; Diffusivity; Disease Progression; Dopamine; Dopamine receptors; Female; Follow-Up Studies; Health care; Humans; Image processing; Image Processing, Computer-Assisted; Magnetic resonance imaging; Male; Medical research; Medicine and Health Sciences; Mesencephalon; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - diagnostic imaging; Neurodegenerative Diseases - pathology; Neuroimaging; NMR; Nuclear magnetic resonance; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson's disease; Parkinsons disease; Patients; Phenotype; Physical Sciences; Physiological aspects; Putamen - metabolism; Putamen - pathology; Reduction; Research and Analysis Methods; Studies; Substantia alba; Substantia nigra; Substantia Nigra - metabolism; Substantia Nigra - pathology; Synuclein; Tau protein; Thalamus; Yu Zhang
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0165540

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.