Shaffer, Joseph J.Ghayoor, AliLong, Jeffrey D.Kim, Regina Eun-YoungLourens, SpencerO’Donnell, Lauren J.Westin, Carl-FredrikRathi, YogeshMagnotta, VincentPaulsen, Jane S.Johnson, Hans J.2020-02-062020-02-062017-03Shaffer, J. J., Ghayoor, A., Long, J. D., Kim, R. E., Lourens, S., O'Donnell, L. J., … Johnson, H. J. (2017). Longitudinal diffusion changes in prodromal and early HD: Evidence of white-matter tract deterioration. Human brain mapping, 38(3), 1460–1477. doi:10.1002/hbm.23465https://hdl.handle.net/1805/21996INTRODUCTION: Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). METHODS: As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. RESULTS: Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. CONCLUSIONS: This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460-1477, 2017. © 2017 Wiley Periodicals, Inc.en-USPublisher PolicyHuntington diseaseDisease progressionProdromalWhite matterDiffusion tractographyDiffusion magnetic resonance imagingMulticenter studyImage processingComputer-assistedArticle