Prodromal Alzheimer's disease: successive emergence of the clinical symptoms
Amieva H, Le Goff M, Millet X, Orgogozo JM, Pérès K, Barberger-Gateau P, et al.;
Commented by , 27 Jan 2009
Aim of the study
Study the duration and pattern of emergence of clinical symptoms before the diagnosis of dementia caused by Alzheimer's disease (AD).
Method
14-year follow-up of a case-control sample selected from the PAQUID cohort. Of the original 3,777 community-dwelling individuals aged 65 or older, 350 where diagnosed with AD over 14 years, with a mean age at diagnosis of 86.2 (SD, 5.6) years. These cases were matched for age, gender and education with 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 performance appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. More global cognitive deficits emerged concomitantly with an increase in memory complaints and depressive symptoms. About 2 years later subjects became slightly dependant in activities of daily living (ADL), until the clinical threshold for dementia was reached.
Professor Gauthier's comments
The authors conclude in the existence of a long-term acquired pathophysiological process that results in clinically measurable symptoms about 12 years before dementia criteria are fulfilled.
The cognitive test that first showed changes was the Isaacs Set Test, consisting of generating words belonging to a semantic category in 15 seconds, followed 2 years later by Wechsler Similarities Test, consisting of saying in what way two things are alike.
Changes in four key instrumental ADL (telephone use, transportation, medication, domestic finances) were detectable 2 to 3 years before dementia was obvious. There is thus opportunity for family practitioners to monitor the cognitive health and autonomy of elderly persons under their care with simple tests.
As far as research for preventive therapies in the prodromal stages of AD, these observations are vital since they give us natural history data that can help plan for intervention studies.
The accompanying editorial by JA Mortimer and RC Peterson (ref. 1) highlights the importance of these clinical observations which are being supplemented in ongoing studies with brain imaging and potential biomarkers. The way we diagnose AD is changing from "dementia first then the most likely cause of dementia is AD" to "AD at different stages, one of them being dementia".
References
1. Mortimer JA, Petersen RC. Detection of prodromal Alzheimer's disease. Annals of Neurology 2008; 64 (5); 479-480