Prodromal XXXX : successive emergence of the clinical symptoms.

@entity308 @entity303 @entity73 @entity51 @entity195 @entity2414
OBJECTIVE: Whereas @entity73 are known to be detectable long before the typical symptoms of @entity195 ( @entity195 ) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before @entity303 . 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 @entity303 phase of @entity195 . 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 @entity195 during the 14 years of follow-up. The cases were matched to 350 elderly control subjects. The evolution of scores on cognitive, functional, and @entity308 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 @entity303 in measures of semantic memory and conceptual formation. Then, more @entity51 appeared that were concomitant with an @entity2414 and @entity308 . About 2 years later, as a consequence of @entity73 , 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 @entity303 phase. INTERPRETATION: This approach, describing the 14 years preceding @entity303 , provides a clear illustration of the particularly long and progressive prodromal phase of @entity195 , and shows the successive emergence of @entity73 , @entity308 , and functional impairment during this phase.
