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Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation
Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D, Kivipelto M, Jessen F et al.. JAMA neurology, 2024-12-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer's Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations. Objective To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states. Evidence review PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms "biomarker" OR "amyloid" OR "tau" OR "neurodegeneration" OR "preclinical" OR "CSF" OR "PET" OR "plasma" AND "Alzheimer's disease." The references of relevant articles were also searched. Findings In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease. Conclusions and relevance The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.
Key findings
- Conclusions and relevance The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia.
- The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop.
- It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD.
- Rather, they should be considered as being at risk for AD.
- The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.
Why it matters
An International Working Group responds to the revised Alzheimer's Association criteria, which can include cognitively normal people with a core 1 biomarker, and argues that Alzheimer's should instead be defined by symptoms and biomarkers together. Citing recent literature showing that "the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline," it recommends calling such people "at risk for AD" rather than labelling them as having the disease, and reserving "presymptomatic AD" for biomarker patterns indicating symptoms are near. This is an expert recommendation based on a literature search, not a new study, and it gives no figures for how many people go on to develop symptoms or when.
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Study details
- Evidence strengthLow
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people 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 | 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 412 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 103.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 6 / 6 | Cited 112.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 43 other studies in this library |
| Still being cited | 4 / 4 | Cited 412 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Giovanni Battista Frisoni: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 77 institution(s) in 19 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39483064) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2024.3770
- PubMed: 39483064
- Original source →
- Free full text: Research at the University of Copenhagen (University of Copenhagen) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Dubois, B., Villain, N., Schneider, L., Fox, N., Campbell, N., Galasko, D., et al. (2024). Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation. JAMA neurology. https://doi.org/10.1001/jamaneurol.2024.3770
Vancouver
Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D, et al. Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation. JAMA neurology. 2024. doi:10.1001/jamaneurol.2024.3770. PMID: 39483064.
BibTeX
@article{dubois2024-39483064,
author = {Dubois, B. and Villain, N. and Schneider, L. and Fox, N. and Campbell, N. and Galasko, D. and Kivipelto, M. and Jessen, F. and others},
title = {{Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation}},
journal = {JAMA neurology},
year = {2024},
doi = {10.1001/jamaneurol.2024.3770},
pmid = {39483064},
url = {https://doi.org/10.1001/jamaneurol.2024.3770}
}
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