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White Matter Degeneration Pathways Associated With Tau Deposition in Alzheimer Disease
Tian J, Raghavan S, Reid RI, Przybelski SA, Lesnick TG, Gebre RK, Graff-Radford J, Schwarz CG et al.. Neurology, 2023-04-17
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives The dynamics of white matter (WM) changes are understudied in Alzheimer disease (AD). Our goal was to study the association between flortaucipir PET and WM health using neurite orientation dispersion and density imaging (NODDI) and evaluate its association with cognitive performance. Specifically, we focused on NODDI's Neurite Density Index (NDI), which aids in capturing axonal degeneration in WM and has greater specificity than single-shell diffusion MRI methods. Method We estimated regional flortaucipir PET standard uptake value ratios (SUVRs) from 3 regions corresponding to Braak stage I, III/IV, and V/VI to capture the spatial distribution pattern of the 3R/4R tau in AD. Then, we evaluated the associations between these measurements and NDIs in 29 candidate WM tracts using Pearson correlation and multiple regression models. Results Based on 223 participants who were amyloid positive (mean age of 78 years and 57.0% male, 119 cognitively unimpaired, 56 mild cognitive impairment, and 48 dementia), the results showed that WM tracts NDI decreased with increasing regional Braak tau SUVRs. Of all the significant WM tracts, the uncinate fasciculus ( r = -0.274 for Braak I, -0.311 for Braak III/IV, and -0.292 for Braak V/VI, p < 0.05) and cingulum adjoining hippocampus ( r = -0.274, -0.288, -0.233, p < 0.05), both tracts anatomically connected to areas of early tau deposition, were consistently found to be within the top 5 distinguishing WM tracts associated with flortaucipir SUVRs. The increase in tau deposition measurable outside the medial temporal lobes in Braak III-VI was associated with a decrease in NDI in the middle and inferior temporal WM tracts. For cognitive performance, WM NDI had similar coefficients of determination ( r 2 = 31%) as regional Braak flortaucipir SUVRs (29%), and together WM NDI and regional Braak flortaucipir SUVRs explained 46% of the variance in cognitive performance. Discussion We found spatially dependent WM degeneration associated with regional flortaucipir SUVRs in Braak stages, suggesting a spatial pattern in WM damage. NDI, a specific marker of axonal density, provides complementary information about disease staging and progression in addition to tau deposition. Measurements of WM changes are important for the mechanistic understanding of multifactorial pathways through which AD causes cognitive dysfunction.
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APA 7th
Tian, J., Raghavan, S., Reid, R. I., Przybelski, S. A., Lesnick, T. G., Gebre, R. K., et al. (2023). White Matter Degeneration Pathways Associated With Tau Deposition in Alzheimer Disease. Neurology. https://doi.org/10.1212/wnl.0000000000207250
Vancouver
Tian J, Raghavan S, Reid RI, Przybelski SA, Lesnick TG, Gebre RK, et al. White Matter Degeneration Pathways Associated With Tau Deposition in Alzheimer Disease. Neurology. 2023. doi:10.1212/wnl.0000000000207250. PMID: 37068958.
BibTeX
@article{tian2023-37068958,
author = {Tian, J. and Raghavan, S. and Reid, R. I. and Przybelski, S. A. and Lesnick, T. G. and Gebre, R. K. and Graff-Radford, J. and Schwarz, C. G. and others},
title = {{White Matter Degeneration Pathways Associated With Tau Deposition in Alzheimer Disease}},
journal = {Neurology},
year = {2023},
doi = {10.1212/wnl.0000000000207250},
pmid = {37068958},
url = {https://doi.org/10.1212/wnl.0000000000207250}
}
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Key findings
- Results Based on 223 participants who were amyloid positive (mean age of 78 years and 57.0% male, 119 cognitively unimpaired, 56 mild cognitive impairment, and 48 dementia), the results showed that WM tracts NDI decreased with increasing regional Braak tau SUVRs.
- Of all the significant WM tracts, the uncinate fasciculus ( r = -0.274 for Braak I, -0.311 for Braak III/IV, and -0.292 for Braak V/VI, p < 0.05) and cingulum adjoining hippocampus ( r = -0.274, -0.288, -0.233, p < 0.05), both tracts anatomically connected to areas of early tau deposition, were consistently found to be within the top 5 distinguishing WM tracts associated with flortaucipir SUVRs.
- The increase in tau deposition measurable outside the medial temporal lobes in Braak III-VI was associated with a decrease in NDI in the middle and inferior temporal WM tracts.
- Discussion We found spatially dependent WM degeneration associated with regional flortaucipir SUVRs in Braak stages, suggesting a spatial pattern in WM damage.
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Study details
- Participants223
- Effect size57.0%
- Evidence strengthLow
How this study scored 59/100
Published in a leading specialty journal. Scored zero for study design 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 34 of the 58 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| 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 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 223 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 37068958) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 34 of the 58 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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