Reduced Synaptic Density in Patients with Lewy Body Dementia: An [ 11 C ] UCB‐J PET Imaging Study
Autor: | Erik H. Danielsen, Per Borghammer, Malene Flensborg Damholdt, Casper Skjærbæk, Jacob Horsager, David J. Brooks, Anna C. Schacht, Hanne Gottrup, Allan K Hansen, Henriette Klit, Katrine B. Andersen |
---|---|
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Parkinson's disease neuropsychology [C-11]UCB‐ Hippocampus J PET s disease 03 medical and health sciences 0302 clinical medicine synapse mental disorders medicine Dementia dementia [ C]UCB-J PET Neuropsychological assessment Cognitive decline medicine.diagnostic_test Lewy body Dementia with Lewy bodies business.industry Neuropsychology Parkinson&apos medicine.disease 030104 developmental biology Neurology Neurology (clinical) business 030217 neurology & neurosurgery |
Zdroj: | Andersen, K B, Hansen, A K, Damholdt, M F, Horsager, J, Skjaerbaek, C, Gottrup, H, Klit, H, Schacht, A C, Danielsen, E H, Brooks, D J & Borghammer, P 2021, ' Reduced Synaptic Density in Patients with Lewy Body Dementia : An [ 11 C-]UCB-J PET Imaging Study ', Movement Disorders, vol. 36, no. 9, pp. 2057-2065 . https://doi.org/10.1002/mds.28617 |
ISSN: | 1531-8257 0885-3185 |
DOI: | 10.1002/mds.28617 |
Popis: | 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 [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]UCB- 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 [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 the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society. |
Databáze: | OpenAIRE |
Externí odkaz: |