Amyloid imaging and Alzheimer's disease: the unsolved cases.

Abstract

This scientific commentary refers to ‘Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer’s disease’, by Chetelat et al. (doi:10.1093/brain/aww159) . The use of advanced imaging technology in sport—international cricket is a good example—has eliminated some old uncertainties but also uncovered new ones that were previously unknown. For example, is it possible for a ball to strike a bat without creating a ‘hot spot’ (local heating through friction detected by infra-red cameras)? The same issue of unearthing novel questions while addressing old ones might be true of the use of imaging technology in dementia. In this issue of Brain , Chetelat and co-workers explore a new question that has emerged from the use of amyloid PET scans in the diagnosis of dementia: how to interpret negative scans in patients who have a clinical phenotype that seems classical for Alzheimer’s disease (Chetelat et al. , 2016). The authors assembled 40 cases with negative amyloid PET scans and a pre-test diagnosis of Alzheimer’s disease from four well-established centres (Caen, Melbourne, Amsterdam and San Francisco). Twenty-one of these cases had a typical amnestic presentation. Comparison groups were constructed from amyloid PET-positive typical Alzheimer’s disease cases and healthy volunteers confirmed to be amyloid PET-negative. Inevitably, some limitations arose from differences in procedures across centres. However, the authors developed and implemented a stringent approach to remove as much inconsistency as possible. Strengths of this multi-centre design included central blinded re-reading of all PET scans and verification of all clinical diagnoses by a predefined review process, based on site visits by two core diagnosticians. The principal advantage of a formalized and effective international collaboration was that the authors were able to assemble enough cases to shed some light on the nature and natural history of amyloid-negative cases thought a priori to have …