Home › Research › Biomarkers
Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, Cosio DMO, Farrell M et al.. JAMA neurology, 2019-08-01
Topic: Amyloid, tau and blood-test diagnosis
Results Of the 60 participants, 35 were women (58%) and 25 were men (42%); median age at inclusion was 73 years (range, 65-85 years). An antecedent rise in Aβ was associated with subsequent changes in tau (1.07 flortaucipir standardized uptake value ratios [SUVr]/PiB-SUVr; 95% CI, 0.13-3.46; P = .02). Tau changes were associated with cognitive changes (-3.28 z scores/SUVR; 95% CI, -6.67 to -0.91; P = .001), covarying baseline Aβ and tau. A serial mediation model demonstrated that the association between initial Aβ and final cognition, measured 7 years later, was mediated by successive changes in Aβ and tau. These findings highlight the importance of repeated tau-PET observations to track disease progression and the importance of repeated amyloid-PET observations to detect the earliest AD pathologic changes.
Key findings
- Results Of the 60 participants, 35 were women (58%) and 25 were men (42%); median age at inclusion was 73 years (range, 65-85 years).
- An antecedent rise in Aβ was associated with subsequent changes in tau (1.07 flortaucipir standardized uptake value ratios [SUVr]/PiB-SUVr; 95% CI, 0.13-3.46; P = .02).
- Tau changes were associated with cognitive changes (-3.28 z scores/SUVR; 95% CI, -6.67 to -0.91; P = .001), covarying baseline Aβ and tau.
- A serial mediation model demonstrated that the association between initial Aβ and final cognition, measured 7 years later, was mediated by successive changes in Aβ and tau.
- These findings highlight the importance of repeated tau-PET observations to track disease progression and the importance of repeated amyloid-PET observations to detect the earliest AD pathologic changes.
Why it matters
Over about 7 years in 60 older adults (median age 73) at the preclinical stage of Alzheimer's, an earlier rise in amyloid on brain scans was associated with later changes in tau, and tau changes were associated with declining thinking scores. A statistical model linked starting amyloid to cognition 7 years later through these successive changes, a pattern consistent with amyloid coming first, then tau, then decline, though it shows association, not cause. The authors say this supports repeated tau-PET to track progression and repeated amyloid-PET to spot the earliest changes; no treatment was tested.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcohort study
- Participants279
- Evidence strengthModerate
How this study scored 77/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 279 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 | 6 / 7 | Cited 860 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 95.6 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 6 / 6 | Cited 66.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 63 other studies in this library |
| Still being cited | 4 / 4 | Cited 358 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Keith A. Johnson: h-index 127 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31157827) |
| Free to read | 2 / 2 | Free to read |
| Total | 77 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2019.1424
- PubMed: 31157827
- 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).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., et al. (2019). Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study. JAMA neurology. https://doi.org/10.1001/jamaneurol.2019.1424
Vancouver
Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, et al. Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study. JAMA neurology. 2019. doi:10.1001/jamaneurol.2019.1424. PMID: 31157827.
BibTeX
@article{hanseeuw2019-31157827,
author = {Hanseeuw, B. J. and Betensky, R. A. and Jacobs, H. I. L. and Schultz, A. P. and Sepulcre, J. and Becker, J. A. and Cosio, D. M. O. and Farrell, M. and others},
title = {{Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study}},
journal = {JAMA neurology},
year = {2019},
doi = {10.1001/jamaneurol.2019.1424},
pmid = {31157827},
url = {https://doi.org/10.1001/jamaneurol.2019.1424}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 19.
Later studies that cite this one
63 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.