School of Medicine Publications and Presentations
Document Type
Article
Publication Date
1-1-2020
Abstract
OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease.
METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period.
RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score.
CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease.
Recommended Citation
Pflanz, C. P., Charquero-Ballester, M., Majid, D. A., Winkler, A. M., Vallée, E., Aron, A. R., ... & Douaud, G. (2020). One-year changes in brain microstructure differentiate preclinical Huntington's disease stages. NeuroImage: Clinical, 25, 102099. https://doi.org/10.1016/j.nicl.2019.102099
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
First Page
102099
Publication Title
NeuroImage. Clinical
DOI
10.1016/j.nicl.2019.102099
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Under a Creative Commons license