Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Reduced Synaptic Density in Patients with Lewy Body Dementia
T2 - An [11C-]UCB-J PET Imaging Study
AU - Andersen, Katrine B
AU - Hansen, Allan K
AU - Damholdt, Malene F
AU - Horsager, Jacob
AU - Skjaerbaek, Casper
AU - Gottrup, Hanne
AU - Klit, Henriette
AU - Schacht, Anna Christina
AU - Danielsen, Erik H
AU - Brooks, David J
AU - Borghammer, Per
N1 - © 2021 International Parkinson and Movement Disorder Society.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Parkinson's disease; dementia; [ C]UCB-J PET; synapse; neuropsychology
KW - [C-11]UCB‐
KW - Parkinson&apos
KW - neuropsychology
KW - dementia
KW - J PET
KW - synapse
KW - s disease
U2 - 10.1002/mds.28617
DO - 10.1002/mds.28617
M3 - Journal article
C2 - 33899255
VL - 36
SP - 2057
EP - 2065
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 9
ER -