Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.29.360552v1?rss=1 Authors: Dadar, M., Miyasaki, J., Duchesne, S., Camicioli, R. Abstract: Background: Freezing of gait (FOG) is a common symptom in Parkinsons Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid {beta} deposition. However, there is a paucity of research on the concurrent impact of white matter damage. Objectives: To assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other. Methods: We used baseline MRI and longitudinal gait data from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid {beta} were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid {beta} on future FOG. Results: SN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid {beta} levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid {beta} levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels. Conclusions: Amyloid {beta} might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology. Copy rights belong to original authors. Visit the link for more info