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Andersen, Katrine B.; Hansen, Allan K.; Damholdt, Malene F.; Horsager, Jacob; Skjærbæk, Casper; Gottrup, Hanne; Klit, Henriette; Schacht, Anna Christina; Danielsen, Erik H.; Brooks, David J.; Borghammer, Per
Movement disorders, September 2021, Volume: 36, Issue: 9Journal Article
ABSTRACT 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 assess 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 age‐matched healthy controls (N = 15). Method Using in vivo PET imaging and the novel synaptic‐vesicle‐glycoprotein 2A (SV2A) radioligand 11CUCB‐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 11CUCB‐J SUVR‐1 were performed. All subjects underwent neuropsychological assessment. Correlations between 11CUCB‐ J 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 11CUCB‐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 11CUCB‐J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. 11CUCB‐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 the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society
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