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  • Title: White matter hyperintensities mediate the impact of amyloid ß on future freezing of gait in Parkinson's disease.
    Author: Dadar M, Miyasaki J, Duchesne S, Camicioli R.
    Journal: Parkinsonism Relat Disord; 2021 Apr; 85():95-101. PubMed ID: 33770671.
    Abstract:
    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 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 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.
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