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Reduced synaptic density in patients with Lewy body dementia: an [11C]UCB-J PET imaging study

Lookup NU author(s): Professor David BrooksORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons Inc., 2021.

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Background: Patients with Parkinson’s disease (PD) often develop dementia but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking. Objective: The objective of this study was to asses the density of synapses in non-demented PD (nPD) subjects (N=21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N=13), and agematched healthy controls (N=15). Method: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J, SUVR-1 values were obtained for 12 pre-defined regions. Volumes-of-interest were defined on MRI T1 scans. Voxel-level between-group comparisons of [11C]UCB-J SUVR-1 were performed. All subjects underwent neuropsychological assessment. Correlations between [11C]UCBJ PET and domain-specific cognitive functioning were examined. Results: nPD patients only demonstrated significantly reduced SUVR-1 values in the substantia nigra (SN) compared to HC. DLB/PDD patients demonstrated reduced SUVR-1 values in SN and all cortical VOIs except for the hippocampus and amygdala. The voxel-based analysis supported the VOI results. Significant correlation was seen between middle frontal gyrus [11C]UCB-J SUVR-1 and performance on tests of executive function. Conclusion: Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. [11C]UCB-J binding in selected cortical VOIs of the DLB/PDD patients correlated with their levels of cognitive function across relevant neuropsychological domains. These findings suggest that loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD.

Publication metadata

Author(s): Andersen KB, Hansen AK, Damholdt MF, Horsager J, Skjærbæk C, Gottrup H, Klit H, Danielsen EH, Brooks DJ, Borghammer P

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2021

Volume: 36

Issue: 9

Pages: 2057-2065

Print publication date: 01/09/2021

Online publication date: 25/04/2021

Acceptance date: 24/03/2021

Date deposited: 08/04/2021

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons Inc.


DOI: 10.1002/mds.28617


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