Imaging the onset and progression of Alzheimer's disease: implications for prevention trials

Excess neuronal loss--atrophy--is an inevitable feature of Alzheimer's disease (AD). Following studies in the early 1990 s demonstrating that non-invasive imaging can be used to visualize excess volume loss, i.e., the consequences of atrophy in AD, a major interest has been improving and validating methods to quantify measures of atrophy from serially acquired magnetic resonance imaging. Here we summarize our experience of measuring the extent and pattern of atrophy to understand disease pathogenesis, particularly through studies of individuals with or destined to develop familial AD; to aid diagnosis; and as an outcome measure for treatment trials. As the field moves toward earlier diagnosis and prevention, we outline the important roles that we believe structural imaging will play alongside other biomarkers both in identifying individuals in the earliest stages of neurodegeneration and assessing the effects of novel therapies.