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Brain Advance Access published online on March 17, 2005
Brain, doi:10.1093/brain/awh451
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 20, 2004
Revised December 8, 2004
Accepted January 27, 2005

Article

The 9 year cognitive decline before dementia of the Alzheimer type: a prospective population-based study

Hélène Amieva 1*, Hélène Jacqmin-Gadda 2, Jean-Marc Orgogozo 3, Nicolas Le Carret 1, Catherine Helmer 1, Luc Letenneur 1, Pascale Barberger-Gateau 1, Colette Fabrigoule 1, and Jean-François Dartigues 3

1 INSERM (Institut National de la Santé et de la Recherche Médicale) Unit 593, University Hospital of Bordeaux, France
2 INSERM E0338, University Hospital of Bordeaux, France
3 INSERM (Institut National de la Santé et de la Recherche Médicale) Unit 593, University Hospital of Bordeaux, France; Department of Neurology, University Hospital of Bordeaux, France

* To whom correspondence should be addressed.
Hélène Amieva, E-mail: helene.amieva{at}isped.u-bordeaux2.fr


  Abstract

Summary Better knowledge of the preclinical phase of Alzheimer's disease would be an important advance to allow earlier treatment of this ominous disease. This prodromal period was investigated in the Paquid cohort by analysing change in cognitive performances at five time points over a 9 year period. Neuropsychological measures including global cognitive functioning (Mini-Mental State Examination), visuo-spatial memory (Benton Visual Retention Test), verbal fluency (Isaacs Set Test) and abstract thinking (Wechsler Similarities Test) were assessed in 215 future Alzheimer's disease subjects and 1050 individuals without dementia. The results showed that cognitive performances of the pre-morbid subjects at baseline were already lower than those of individuals without dementia (1.4 points less on the Mini-Mental State Examination; 1.8 points less on the Benton Visual Retention Test; 4 points less on the Isaacs Set Test and 0.8 points less on the Wechsler Similarities Test). For some neuropsychological tests, an acceleration of the decline occurred ~3 years before the diagnosis and, for each test, the course of decline was modulated by education level. These findings show that abnormally low performances can be evidenced 9 years before the clinical diagnosis of Alzheimer's disease in several domains of cognition beyond memory and that cognitive change over time can be influenced by education.

Keywords: dementia; subclinical phase; cognitive decline; prospective study.
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