Neuroimaging in Glucocerebrosidase‐Associated Parkinsonism: A Systematic Review

Abstract

Background Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting carriers of GBA mutations/variants (GBA‐NMC) constitute a potential PD preclinical population, whereas PD patients carrying some GBA mutations/variants (GBA‐PD) have a higher risk of a more aggressive disease course. Different neuroimaging techniques are emerging as potential biomarkers in PD and have been used to study GBA‐associated parkinsonism. Objective The aim is to critically review studies applying neuroimaging to GBA‐associated parkinsonism. Methods Literature search was performed using PubMed and EMBASE databases (last search February 7, 2022). Studies reporting neuroimaging findings in GBA‐PD, GD with and without parkinsonism, and GBA‐NMC were included. Results Thirty‐five studies were included. In longitudinal studies, GBA‐PD patients show a more aggressive disease than iPD at both structural magnetic resonance imaging and 123‐fluoropropylcarbomethoxyiodophenylnortropane single‐photon emission computed tomography. Fluorodeoxyglucose‐positron emission tomography and brain perfusion studies reported a greater cortical involvement in GBA‐PD compared to iPD. Overall, contrasting evidence is available regarding GBA‐NMC for imaging and clinical findings, although subtle differences have been reported compared with healthy controls with no mutations. Conclusions Although results must be interpreted with caution due to limitations of the studies, in line with previous clinical observations, GBA‐PD showed a more aggressive disease progression in neuroimaging longitudinal studies compared to iPD. Cognitive impairment, a “clinical signature” of GBA‐PD, seems to find its neuroimaging correlate in the greater cortical burden displayed by these patients as compared to iPD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach

“…Conventional and advanced imaging techniques constitute another interesting tool used to provide objective in vivo measurements of brain dysfunction, which may predate clinical manifestations of disease within genetically stratified cohorts [73]. For a comprehensive review on the topic, the reader is directed elsewhere [73].…”

“…Conventional and advanced imaging techniques constitute another interesting tool used to provide objective in vivo measurements of brain dysfunction, which may predate clinical manifestations of disease within genetically stratified cohorts [73]. For a comprehensive review on the topic, the reader is directed elsewhere [73]. Below, we will present the most recent neuroimaging studies evaluating GBA1-NMC and LRRK2-NMC, highlighting the successful/unsuccessful application of such imaging techniques as prediction markers.…”

Glucocerebrosidase mutations and Parkinson disease

“…The finding of a more aggressive progression in GBA1 -PD cases has also been supported by cerebral blood flow (Goker-Alpan et al 2012 ; Cilia et al 2016 ) and FDG-PET studies (Greuel et al 2020 ; Schindlbeck et al 2020 ). Imaging in GBA1-PD has recently been reviewed (Filippi et al 2022 ).…”

Free‐Water Imaging of the Substantia Nigra in GBA Pathogenic Variant Carriers

“…22 Thus, the existence of a "nigrostriatal signature" of GBA pathogenic variants remains controversial. 25 More investigations with advanced imaging methods are warranted to sensitively reveal nigrostriatal damage in GBA-NMC and GBA-PD.…”