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Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frölich L, Schönknecht P, Ito K et al.. NeuroImage, 2002-09-01
Topic: Amyloid, tau and blood-test diagnosis
A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.
Key findings
- In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex.
- These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging.
- Women with probable AD had significantly more frontal metabolic impairment than men.
- All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset.
- In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.
Why it matters
Across eight centres, an automated, age-adjusted score of brain glucose PET scans separated 395 people with probable Alzheimer's disease from 110 healthy controls with 93% sensitivity and specificity for mild to moderate disease, and 84% sensitivity at 93% specificity for very mild disease (MMSE 24 or better). The patients were compared only with healthy people, not with other dementias, and diagnoses were clinical ("probable"). The authors conclude that the method "can be used potentially as a sensitive biomarker for early AD diagnosis", not that it is ready for routine use.
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Study details
- Participants395
- Evidence strengthLow
How this study scored 59/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NeuroImage) |
| Journal's citation record | 4 / 4 | NeuroImage: journal h-index 523 (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 | 1 / 5 | 2002 — older than 20 years, still counted |
| Sample size | 2 / 4 | 395 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 835 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 32.1 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 16.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 56 other studies in this library |
| Still being cited | 3 / 4 | Cited 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Elke Kalbe: h-index 55 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12482085) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
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Read the original
- DOI: 10.1006/nimg.2002.1208
- PubMed: 12482085
- Original source →
- Free full text: Open Repository and Bibliography (University of Liège) →
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
Herholz, K., Salmon, E., Perani, D., Baron, J. C., Holthoff, V., Frölich, L., et al. (2002). Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage. https://doi.org/10.1006/nimg.2002.1208
Vancouver
Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frölich L, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage. 2002. doi:10.1006/nimg.2002.1208. PMID: 12482085.
BibTeX
@article{herholz2002-12482085,
author = {Herholz, K. and Salmon, E. and Perani, D. and Baron, J. C. and Holthoff, V. and Frölich, L. and Schönknecht, P. and Ito, K. and others},
title = {{Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET}},
journal = {NeuroImage},
year = {2002},
doi = {10.1006/nimg.2002.1208},
pmid = {12482085},
url = {https://doi.org/10.1006/nimg.2002.1208}
}
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