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Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum
Timmers T, Ossenkoppele R, Wolters EE, Verfaillie SCJ, Visser D, Golla SSV, Barkhof F, Scheltens P et al.. Alzheimer's research & therapy, 2019-07-04
Topic: Amyloid, tau and blood-test diagnosis
Background Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [ 18 F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [ 18 F]flortaucipir PET to generate non-displaceable binding potential (BP ND ) maps. We extracted average [ 18 F]flortaucipir BP ND entorhinal, Braak III-IV (limbic) and Braak V-VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [ 18 F]flortaucipir BP ND ROIs as independent and GM density (ROI or voxelwise) as dependent variable. Results In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [ 18 F]flortaucipir BP ND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [ 18 F]flortaucipir BP ND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p < 0.001). Greater [ 18 F]flortaucipir BP ND in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p < 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [ 18 F]Flortaucipir BP ND in ROI Braak I-II was not associated with GM density loss anywhere. When quantifying [ 18 F]flortaucipir BP ND across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [ 18 F]flortaucipir BP ND and GM density (standardized βs ranging from - 0.24 to 0.02, all p > 0.05). Conclusions In MCI/AD patients, [ 18 F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.
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APA 7th
Timmers, T., Ossenkoppele, R., Wolters, E. E., Verfaillie, S. C. J., Visser, D., Golla, S. S. V., et al. (2019). Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-019-0510-3
Vancouver
Timmers T, Ossenkoppele R, Wolters EE, Verfaillie SCJ, Visser D, Golla SSV, et al. Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum. Alzheimer's research & therapy. 2019. doi:10.1186/s13195-019-0510-3. PMID: 31272512.
BibTeX
@article{timmers2019-31272512,
author = {Timmers, T. and Ossenkoppele, R. and Wolters, E. E. and Verfaillie, S. C. J. and Visser, D. and Golla, S. S. V. and Barkhof, F. and Scheltens, P. and others},
title = {{Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum}},
journal = {Alzheimer's research \& therapy},
year = {2019},
doi = {10.1186/s13195-019-0510-3},
pmid = {31272512},
url = {https://doi.org/10.1186/s13195-019-0510-3}
}
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Key findings
- Results In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [ 18 F]flortaucipir BP ND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001).
- In MCI/AD, greater [ 18 F]flortaucipir BP ND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p < 0.001).
- Greater [ 18 F]flortaucipir BP ND in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p < 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [ 18 F]Flortaucipir BP ND in ROI Braak I-II was not associated with GM density loss anywhere.
- When quantifying [ 18 F]flortaucipir BP ND across brain lobes, we observed both local and distant associations with GM atrophy.
- In controls, there were no significant associations between [ 18 F]flortaucipir BP ND and GM density (standardized βs ranging from - 0.24 to 0.02, all p > 0.05).
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Study details
- Participants100
- Evidence strengthLow
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 (Alzheimer's research & therapy) |
| 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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 100 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 31272512) |
| Free to read | 2 / 2 | Free to read |
| 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 | — |
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