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Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study
Andersen KB, Hansen AK, Damholdt MF, Horsager J, Skjaerbaek C, Gottrup H, Klit H, Schacht AC et al.. Movement disorders : official journal of the Movement Disorder Society, 2021-04-25
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
- 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.
Study details
- Participants21
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 29 of the 58 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Movement disorders : official journal of the Movement Disorder Society) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 21 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33899255) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 29 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 29 of the 58 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Andersen, K. B., Hansen, A. K., Damholdt, M. F., Horsager, J., Skjaerbaek, C., Gottrup, H., et al. (2021). Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study. Movement disorders : official journal of the Movement Disorder Society. https://doi.org/10.1002/mds.28617
Vancouver
Andersen KB, Hansen AK, Damholdt MF, Horsager J, Skjaerbaek C, Gottrup H, et al. Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study. Movement disorders : official journal of the Movement Disorder Society. 2021. doi:10.1002/mds.28617. PMID: 33899255.
BibTeX
@article{andersen2021-33899255,
author = {Andersen, K. B. and Hansen, A. K. and Damholdt, M. F. and Horsager, J. and Skjaerbaek, C. and Gottrup, H. and Klit, H. and Schacht, A. C. and others},
title = {{Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study}},
journal = {Movement disorders : official journal of the Movement Disorder Society},
year = {2021},
doi = {10.1002/mds.28617},
pmid = {33899255},
url = {https://doi.org/10.1002/mds.28617}
}
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