RT Journal Article
SR Electronic
T1 Amyloid ß Impacts Future Freezing of Gait in Parkinson’s Disease Via White Matter Hyperintensities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.29.360552
DO 10.1101/2020.10.29.360552
A1 Mahsa Dadar
A1 Janis Miyasaki
A1 Simon Duchesne
A1 Richard Camicioli
YR 2020
UL http://biorxiv.org/content/early/2020/10/29/2020.10.29.360552.abstract
AB Background Freezing of gait (FOG) is a common symptom in Parkinson’s Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β 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 β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.Results SN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.Conclusions Amyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.Competing Interest StatementThe authors have declared no competing interest.