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Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum
Iaccarino L, La Joie R, Edwards L, Strom A, Schonhaut DR, Ossenkoppele R, Pham J, Mellinger T et al.. Cerebral cortex (New York, N.Y. : 1991), 2021-01-01
Topic: Amyloid, tau and blood-test diagnosis
A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer's disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.5) diagnosed with AD dementia or mild cognitive impairment due to AD and available 11C-PiB (PIB), 18F-Flortaucipir (FTP),18F-FDG-PET, and 3T-MRI, and 31 amyloid-positive, cognitively normal participants (age 77.3 ± 6.5, no FDG-PET). W-score voxel-wise deviation maps were created and binarized for each imaging-modality (W > 1.64, P < 0.05) adjusting for age, sex, and total intracranial volume (sMRI-only) using amyloid-negative cognitively normal adults. For symptomatic patients, FDG-PET and atrophy W-maps were combined into neurodegeneration maps (ND). Aβ-pathology showed the greatest proportion of cortical gray matter suprathreshold voxels (spatial extent) for both symptomatic and asymptomatic participants (median 94-55%, respectively), followed by tau (79-11%) and neurodegeneration (41-3%). Amyloid > tau > neurodegeneration was the most frequent hierarchy for both groups (79-77%, respectively), followed by tau > amyloid > neurodegeneration (13-10%) and amyloid > neurodegeneration > tau (6-13%). For symptomatic participants, most abnormal voxels were PIB+/FTP+/ND- (median 35%), and the great majority of ND+ voxels (91%) colocalized with molecular pathology. Amyloid spatially exceeded tau and neurodegeneration, with individual heterogeneities. Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms.
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APA 7th
Iaccarino, L., La Joie, R., Edwards, L., Strom, A., Schonhaut, D. R., Ossenkoppele, R., et al. (2021). Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum. Cerebral cortex (New York, N.Y. : 1991). https://doi.org/10.1093/cercor/bhaa184
Vancouver
Iaccarino L, La Joie R, Edwards L, Strom A, Schonhaut DR, Ossenkoppele R, et al. Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum. Cerebral cortex (New York, N.Y. : 1991). 2021. doi:10.1093/cercor/bhaa184. PMID: 32808011.
BibTeX
@article{iaccarino2021-32808011,
author = {Iaccarino, L. and La Joie, R. and Edwards, L. and Strom, A. and Schonhaut, D. R. and Ossenkoppele, R. and Pham, J. and Mellinger, T. and others},
title = {{Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum}},
journal = {Cerebral cortex (New York, N.Y. : 1991)},
year = {2021},
doi = {10.1093/cercor/bhaa184},
pmid = {32808011},
url = {https://doi.org/10.1093/cercor/bhaa184}
}
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Key findings
- Aβ-pathology showed the greatest proportion of cortical gray matter suprathreshold voxels (spatial extent) for both symptomatic and asymptomatic participants (median 94-55%, respectively), followed by tau (79-11%) and neurodegeneration (41-3%).
- Amyloid > tau > neurodegeneration was the most frequent hierarchy for both groups (79-77%, respectively), followed by tau > amyloid > neurodegeneration (13-10%) and amyloid > neurodegeneration > tau (6-13%).
- For symptomatic participants, most abnormal voxels were PIB+/FTP+/ND- (median 35%), and the great majority of ND+ voxels (91%) colocalized with molecular pathology.
- Amyloid spatially exceeded tau and neurodegeneration, with individual heterogeneities.
- Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms.
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Study details
- Participants81
- Evidence strengthLow
How this study scored 47/100
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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cerebral cortex (New York, N.Y. : 1991)) |
| 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 | 1 / 5 | Rated “low” 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 | 81 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 32808011) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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