Diagnosis and biomarkers of predementia in Alzheimer's disease

In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.

The present work was supported by Conselho Nacional de Pesquisa Científica (CNPq, Project 554535/2005-0), Alzheimer’s Association (NIRG-08-90688), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Project 02/13633-7). The Laboratory of Neuroscience (LIM-27) receives financial support from Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS).