PET amyloid imaging as a tool for early diagnosis and identifying patients at risk for progression to Alzheimer's disease

The development in 1984 of consensus criteria [1] for diagnosis of Alzheimer's disease (AD) capped a period of evolving knowledge that AD could be differentiated not only from normal aging but also from other causes of neurodegenerative dementias. On average, clinical diagnosis using these consensus criteria is approximately 81% sensitive and 70% specific compared to the gold standard, pathology at autopsy [2], a performance that equals or exceeds the performance of proposed diagnostic criteria for many other neurodegenerative diseases [2,3].Nevertheless, there remains both room and a need for improvement in diagnostic accuracy. Up to 20% of subjects clinically diagnosed with AD do not have AD pathology at autopsy [4-6], a percentage that is essentially unchanged from the estimate in the 1984 consensus publication [1]. In addition, under-diagnosis in the community setting is significant. Approximately 10% of community-dwelling elderly have undiagnosed dementia [7,8] and community physicians may fail to diagnose up to 33% of individuals with mild dementia [8].Perhaps the biggest limitation in current practice is a reliance on the presentation and progression of symptoms to identify an AD phenotype. This inherently leads to delays in diagnosis as physicians must wait for symptoms to appear and must track progressive decline over time. However, the past 25 years have seen dramatic improvements in technology and understanding of biomarkers that offer potential to improve this diagnostic algorithm. As a result, new draft criteria [9,10] have proposed that diagnosis can be enhanced by use of biomarkers to increase certainty, and, in early stages, to identify prodromal AD. This approach has the potential to allow earlier and more specific diagnosis and will possibly identify patients with AD before the point where irreversible damage precludes effective treatment [11].A number of different biomarkers, including atrophy on magnetic resonance imaging (MRI), regional metaboli