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Prodromal Alzheimer's disease: successive emergence of the clinical symptoms
Amieva H, Le Goff M, Millet X, Orgogozo JM, Pérès K, Barberger-Gateau P, Jacqmin-Gadda H, Dartigues JF.. Annals of neurology, 2008-11-01
Topic: Amyloid, tau and blood-test diagnosis
Objective Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimer's disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow-up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14-year period of follow-up before the dementia phase of AD. Methods This study relies on a case-control sample selected from the PAQUID cohort. Of the 3,777 initial subjects of the cohort, 350 subjects experienced development of AD during the 14 years of follow-up. The cases were matched to 350 elderly control subjects. The evolution of scores on cognitive, functional, and depression scales was described throughout the 14-year follow-up using a semiparametric extension of the mixed-effects linear model. Results The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. Then, more global deficits appeared that were concomitant with an increase in memory complaints and depressive symptoms. About 2 years later, as a consequence of cognitive dysfunction, the subjects started to become slightly dependent in their activities of daily living. In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase. Interpretation This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase.
Key findings
- Results The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation.
- In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase.
Why it matters
In 350 people from the PAQUID cohort who developed Alzheimer's over 14 years, compared with 350 matched older adults who did not, the first measurable decline appeared "as early as 12 years before dementia" in semantic memory and conceptual formation. The study describes broader thinking problems emerging next, alongside more memory complaints and depressive symptoms, then slight dependence in daily activities about 2 years later, and a marked worsening in the final 3 years before diagnosis. This maps the order in which symptoms emerged on average in this group. It does not predict who will develop dementia, and it tested no treatment.
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Study details
- Study designcase-control study
- Participants350
- Evidence strengthModerate
How this study scored 65/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (OpenAlex, 2026-10-29) |
| 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 | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 350 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 738 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 36.9 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 4 / 6 | Cited 19.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 41 other studies in this library |
| Still being cited | 3 / 4 | Cited 86 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jean François Dartigues: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19067364) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 100 | — |
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Read the original
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Amieva, H., Le Goff, M., Millet, X., Orgogozo, J. M., Pérès, K., Barberger-Gateau, P., et al. (2008). Prodromal Alzheimer's disease: successive emergence of the clinical symptoms. Annals of neurology. https://doi.org/10.1002/ana.21509
Vancouver
Amieva H, Le Goff M, Millet X, Orgogozo JM, Pérès K, Barberger-Gateau P, et al. Prodromal Alzheimer's disease: successive emergence of the clinical symptoms. Annals of neurology. 2008. doi:10.1002/ana.21509. PMID: 19067364.
BibTeX
@article{amieva2008-19067364,
author = {Amieva, H. and Le Goff, M. and Millet, X. and Orgogozo, J. M. and Pérès, K. and Barberger-Gateau, P. and Jacqmin-Gadda, H. and Dartigues, J. F.},
title = {{Prodromal Alzheimer's disease: successive emergence of the clinical symptoms}},
journal = {Annals of neurology},
year = {2008},
doi = {10.1002/ana.21509},
pmid = {19067364},
url = {https://doi.org/10.1002/ana.21509}
}
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