Journal
PARKINSONISM & RELATED DISORDERS
Volume 85, Issue -, Pages 95-101Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2021.02.031
Keywords
Amyloid beta; White matter hyperintensities; Mediation analysis; Dopamine transporter imaging; Freezing of gait
Categories
Funding
- Canadian Consortium on Neurodegeneration in Aging
- Alzheimer Society Research Program (ASRP)
- Canadian Institutes of Health Research
- Alzheimer Society of Canada
- Sanofi
- Women's Brain Health Initiative
- University Hospital Foundation
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By analyzing MRI and gait data of de novo Parkinson's Disease patients, the study found that amyloid beta impacts future freezing of gait by increasing white matter pathology load, independently of substantia nigra atrophy and striatal dopamine transporter activity levels.
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 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 423 de novo PD patients 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.
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