Amyloid imaging and memory change for prediction of cognitive impairment

The development of positron emission tomography (PET) amyloid imaging radiotracers has allowed the in vivo measurement of fibrillar β-amyloid (Aβ) throughout the brain. Amyloid imaging is contributing to the early detection of pathology and diagnosis of Alzheimer's disease (AD), to the selection and therapeutic monitoring of patients in clinical trials, and to differential diagnosis among dementia subtypes. In addition, it is enhancing our understanding of the role of Aβ in the temporal course of disease by allowing prospective assessment of early pathological changes and the cognitive correlates of these changes in Aβ deposition. PET imaging of fibrillar Aβ provides many opportunities for early diagnosis of cognitive impairment and the understanding of disease progression, but the prediction of clinical outcomes in cognitively unimpaired individuals remains challenging.The large percentage of individuals who have substantial levels of Aβ but remain cognitively normal is a potential limitation in the use of amyloid imaging for prediction of clinical outcomes. Thirty to fifty percent of individuals who are clinically normal at death have sufficient Aβ plaques at autopsy to meet pathological criteria for AD [1,2]. Similarly, PET imaging studies also show that about 30% [3-7] of cognitively normal individuals have varying levels of increased Aβ on imaging. Some investigators argue that cognitively normal individuals with AD pathology are in a preclinical stage of AD [8-10]. However, we [11] and others [12] have shown that antemortem cognitive change in this group of 'asymptomatic AD' individuals does not differ significantly from cognitively normal individuals without AD pathology at autopsy, in contrast to the marked memory decline evident in those who develop subsequent cognitive impairment (Figure 1a).The challenge posed by these asymptomatic AD individuals in the application of PET Aβ imaging for clinical diagnosis has led some to question whether these tools will