Potential conflict of interest: Nothing to report.
Prodromal Alzheimer's disease: Successive emergence of the clinical symptoms†
Version of Record online: 9 DEC 2008
Copyright © 2008 American Neurological Association
Annals of Neurology
Volume 64, Issue 5, pages 492–498, November 2008
How to Cite
Amieva, H., Le Goff, M., Millet, X., Orgogozo, J. M., Pérès, K., Barberger-Gateau, P., Jacqmin-Gadda, H. and Dartigues, J. F. (2008), Prodromal Alzheimer's disease: Successive emergence of the clinical symptoms. Ann Neurol., 64: 492–498. doi: 10.1002/ana.21509
- Issue online: 9 DEC 2008
- Version of Record online: 9 DEC 2008
- Manuscript Accepted: 11 JUL 2008
- Manuscript Revised: 9 JUL 2008
- Manuscript Received: 20 MAR 2008
- ARMA (Bordeaux)
- Caisse Nationale d'Assurance Maladie des Travailleurs Salariés (CNAMTS)
- Conseil Général de la Dordogne
- Conseil Général de la Gironde
- Conseil Régional d'Aquitaine
- Fondation de France; France Alzheimer (Paris)
- GIS Longévité
- Institut National de la Santé et de la Recherche Médicale (INSERM)
- Mutuelle Générale de l'Education Nationale (MGEN)
- Mutualité Sociale Agricole (MSA)
- NOVARTIS Pharma (France)
- SCOR Insurance (France)
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.
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.
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.
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. Ann Neurol 2008;64:492–498