Home › Research › Biomarkers
Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity
Jack CR, Wiste HJ, Weigand SD, Knopman DS, Lowe V, Vemuri P, Mielke MM, Jones DT et al.. Neurology, 2013-10-16
Topic: Amyloid, tau and blood-test diagnosis
Objective To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity. Methods Cognitively normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each time point, were eligible for analysis (n = 207). Twelve subjects with Alzheimer disease dementia were included for comparison. Results Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group. Eleven of the 26 incident amyloid-positive subjects had abnormal hippocampal volume, FDG-PET, or both at baseline. Conclusions The incidence of amyloid PET positivity is approximately 13% per year among CN participants over age 70 sampled from a population-based cohort. In 15/26 (58%), incident amyloid positivity occurred prior to abnormalities in FDG-PET and hippocampal volume. However, 11/26 (42%) incident amyloid-positive subjects had evidence of neurodegeneration prior to incident amyloid positivity. These 11 could be subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau-mediated neurodegeneration who newly entered the amyloid pathway. Our findings suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile pathways to preclinical AD exist.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Jack, C. R., Wiste, H. J., Weigand, S. D., Knopman, D. S., Lowe, V., Vemuri, P., et al. (2013). Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. Neurology. https://doi.org/10.1212/01.wnl.0000435556.21319.e4
Vancouver
Jack CR, Wiste HJ, Weigand SD, Knopman DS, Lowe V, Vemuri P, et al. Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. Neurology. 2013. doi:10.1212/01.wnl.0000435556.21319.e4. PMID: 24132377.
BibTeX
@article{jack2013-24132377,
author = {Jack, C. R. and Wiste, H. J. and Weigand, S. D. and Knopman, D. S. and Lowe, V. and Vemuri, P. and Mielke, M. M. and Jones, D. T. and others},
title = {{Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity}},
journal = {Neurology},
year = {2013},
doi = {10.1212/01.wnl.0000435556.21319.e4},
pmid = {24132377},
url = {https://doi.org/10.1212/01.wnl.0000435556.21319.e4}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Objective To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity.
- Results Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity.
- Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group.
- Our findings suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile pathways to preclinical AD exist.
Why it matters
Among cognitively normal older adults, new amyloid PET positivity occurred at about 13% per year, and in many cases it appeared before abnormalities in FDG-PET or hippocampal volume, though some had neurodegeneration first. This describes the order of biomarker changes and does not offer a treatment, cure, or prevention.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Participants207
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| 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 | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 207 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 | 5 / 7 | Cited 199 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.3 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 17.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ronald Carl Petersen: h-index 209 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24132377) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/01.wnl.0000435556.21319.e4
- PubMed: 24132377
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 25.
Later studies that cite this one
19 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Biomarkers
Also tagged “classification”
835 studies in the library carry the topic tag “classification”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 835 tagged studies.