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Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study
Josephs KA, Weigand SD, Whitwell JL.. Neurology, 2022-03-21
Topic: Amyloid, tau and blood-test diagnosis
Background and objective Individuals with biomarker evidence of β-amyloid (Aβ) deposition are increasingly being enrolled in clinical treatment trials but there is a need to identify markers to predict which of these individuals will also develop tau deposition. We aimed to determine whether Aβ-positive individuals can remain tau-negative for at least 5 years and identify characteristics that could distinguish between these individuals and those who develop high tau within this period. Methods Tau PET positivity was defined using a Gaussian mixture model with log-transformed standard uptake value ratio values from 7 temporal and medial parietal regions using all participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with flortaucipir PET. Tau PET scans were classified as normal if the posterior probability of elevated tau was less than 1%. Aβ PET positivity was defined based on ADNI cutpoints. We identified all Aβ-positive individuals from ADNI who had normal tau PET more than 5 years after their first abnormal Aβ PET (amyloid with low tau [ALT] group) and all Aβ-positive individuals with abnormal tau PET within 5 years (biomarker AD). In a case-control design, logistic regression was used to model the odds of biomarker AD vs ALT accounting for sex, age, APOE ε4 carriership, Aβ Centiloid, and hippocampal volume. Results We identified 45 individuals meeting criteria for ALT and 157 meeting criteria for biomarker AD. The ALT group had a lower proportion of APOE ε4 carriers, lower Aβ Centiloid, larger hippocampal volumes, and more preserved cognition, and were less likely to develop dementia, than the biomarker AD group. APOE ε4, higher Aβ Centiloid, and hippocampal atrophy were independently associated with increased odds of abnormal tau within 5 years. A Centiloid value of 50 effectively discriminated biomarker AD and ALT with 80% sensitivity and specificity. The majority of the ALT participants did not develop dementia throughout the 5-year interval. Discussion Aβ-positive individuals can remain tau-negative for at least 5 years. Baseline characteristics can help identify these ALT individuals who are less likely to develop dementia. Conservative Aβ cutpoints should be utilized for clinical trials to better capture individuals with high risk of developing biomarker AD.
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APA 7th
Josephs, K. A., Weigand, S. D., & Whitwell, J. L. (2022). Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. Neurology. https://doi.org/10.1212/wnl.0000000000200287
Vancouver
Josephs KA, Weigand SD, Whitwell JL. Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. Neurology. 2022. doi:10.1212/wnl.0000000000200287. PMID: 35314506.
BibTeX
@article{josephs2022-35314506,
author = {Josephs, K. A. and Weigand, S. D. and Whitwell, J. L.},
title = {{Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000200287},
pmid = {35314506},
url = {https://doi.org/10.1212/wnl.0000000000200287}
}
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Key findings
- Results We identified 45 individuals meeting criteria for ALT and 157 meeting criteria for biomarker AD.
- APOE ε4, higher Aβ Centiloid, and hippocampal atrophy were independently associated with increased odds of abnormal tau within 5 years.
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Study details
- Study designcase-control study
- Participants45
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for 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 37 of the 58 points we could judge it on, which is 64 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 | 6 / 12 | A case-control study |
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 45 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 35314506) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 37 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 37 of the 58 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
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