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.
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.
Authors: Laura A Rabin; Colette M Smart; Paul K Crane; Rebecca E Amariglio; Lorin M Berman; Mercé Boada; Rachel F Buckley; Gaël Chételat; Bruno Dubois; Kathryn A Ellis; Katherine A Gifford; Angela L Jefferson; Frank Jessen; Mindy J Katz; Richard B Lipton; Tobias Luck; Paul Maruff; Michelle M Mielke; José Luis Molinuevo; Farnia Naeem; Audrey Perrotin; Ronald C Petersen; Lorena Rami; Barry Reisberg; Dorene M Rentz; Steffi G Riedel-Heller; Shannon L Risacher; Octavio Rodriguez; Perminder S Sachdev; Andrew J Saykin; Melissa J Slavin; Beth E Snitz; Reisa A Sperling; Caroline Tandetnik; Wiesje M van der Flier; Michael Wagner; Steffen Wolfsgruber; Sietske A M Sikkes Journal: J Alzheimers Dis Date: 2015-09-24 Impact factor: 4.472
Authors: B C Dickerson; T R Stoub; R C Shah; R A Sperling; R J Killiany; M S Albert; B T Hyman; D Blacker; L Detoledo-Morrell Journal: Neurology Date: 2011-04-13 Impact factor: 9.910
Authors: Andrea L C Schneider; Rebecca F Gottesman; Thomas Mosley; Alvaro Alonso; David S Knopman; Josef Coresh; A Richey Sharrett; Elizabeth Selvin Journal: Neuroepidemiology Date: 2012-10-22 Impact factor: 3.282
Authors: Napatkamon Ayutyanont; Jessica B S Langbaum; Suzanne B Hendrix; Kewei Chen; Adam S Fleisher; Michel Friesenhahn; Michael Ward; Camilo Aguirre; Natalia Acosta-Baena; Lucìa Madrigal; Claudia Muñoz; Victoria Tirado; Sonia Moreno; Pierre N Tariot; Francisco Lopera; Eric M Reiman Journal: J Clin Psychiatry Date: 2014-06 Impact factor: 4.384
Authors: Robert S Wilson; Patricia A Boyle; Eisuke Segawa; Lei Yu; Christopher T Begeny; Sophia E Anagnos; David A Bennett Journal: Psychol Aging Date: 2013-02-18