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Title: Reduced cortical cholinergic innervation measured using [18F]-FEOBV PET imaging correlates with cognitive decline in mild cognitive impairment.
Austin Authors: Xia, Ying;Eeles, Eamonn;Fripp, Jurgen;Pinsker, Donna;Thomas, Paul;Latter, Melissa;Doré, Vincent ;Fazlollahi, Amir;Bourgeat, Pierrick;Villemagne, Victor L ;Coulson, Elizabeth J;Rose, Stephen
Affiliation: Dementia & Neuro Mental Health Research Unit, UQCCR, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia..
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia..
School of Medicine, Northside Clinical School, The Prince Charles Hospital, Brisbane, QLD, Australia..
The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, QLD, Australia..
Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia..
Internal Medicine Service, The Prince Charles Hospital, Brisbane, QLD, Australia..
School of Psychology, The University of Queensland, Brisbane, QLD, Australia..
Austin Health
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA..
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia..
Issue Date: 24-Mar-2022
Date: 2022
Publication information: NeuroImage. Clinical 2022; 34: 102992
Abstract: Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profiles associated with dementia, particularly at a prodromal stage. In this study, we used the radiotracer [18F]-fluoroethoxybenzovesamicol (FEOBV) as a direct measure of cholinergic terminal integrity and investigated its value for the assessment of cholinergic denervation in the cortex and associated cognitive deficits. Eighteen participants (8 with mild cognitive impairment (MCI) and 10 cognitively unimpaired controls) underwent neuropsychological assessment and brain imaging using FEOBV and [18F]-florbetaben for amyloid-β imaging. The MCI group showed a significant global reduction of FEOBV retention in the cortex and in the parietal and occipital cortices specifically compared to the control group. The global cortical FEOBV retention of all participants positively correlated with the BF, hippocampus and grey matter volumes, but no association was found between the global FEOBV retention and amyloid-β status. Topographic profiles from voxel-wise analysis of FEOBV images revealed significant positive correlations with the cognitive domains associated with the underlying cortical areas. Overlapping profiles of decreased FEOBV were identified in correlation with impairment in executive function, attention and language, which covered the anterior cingulate gyrus, olfactory cortex, calcarine cortex, middle temporal gyrus and caudate nucleus. However, the absence of cortical atrophy in these areas suggested that reduced cholinergic terminal integrity in the cortex is an important factor underlying the observed cognitive decline in early dementia. Our results provide support for the utility and validity of FEOBV PET for quantitative assessment of region-specific cholinergic terminal integrity that could potentially be used for early detection of cholinergic dysfunction in dementia following further validation in larger cohorts.
DOI: 10.1016/j.nicl.2022.102992
ORCID: 0000-0002-8051-0558
Journal: NeuroImage. Clinical
PubMed URL: 35344804
PubMed URL:
Type: Journal Article
Subjects: Basal forebrain
Cholinergic system
Mild cognitive impairment
PET imaging
Appears in Collections:Journal articles

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