The diagnostic value of FDG and amyloid PET in Alzheimer's disease—A systematic review

Highlights: • Systematic review of 60 papers from 2001 to 2017. • Highlights the importance of accurate imaging biomarkers in AD in improving diagnostic accuracy, accurate clinical trials and patient outcome. • Lack of standardised thresholds for positivity in both FDG and amyloid PET restrict what can be inferred from clinical trials. • Importance of accurate diagnosis of AD, and the role of imaging in this process, will heighten with the development of disease-modifying agents. - Abstract: Purpose: By 2050 it is projected that 115 million people worldwide will have Alzheimer's Disease (AD) [1]. Recent attempts have been made to redefine the diagnostic criteria of AD to include markers of neurodegeneration – measurable by FDG-PET – and markers of amyloid accumulation – measurable by amyloid-PET. Materials and methods: A systematic review of the literature was performed to examine the current diagnostic use of amyloid and FDG PET. MEDLINE and EMBASE databases and the Cochrane Database were searched for relevant papers Results and discussion: This search resulted in twenty-nine papers on amyloid imaging, twenty-three papers on FDG-PET and eight papers which utilized both techniques. Both modalities are considered in turn with regards to their diagnostic accuracy, their role in mild cognitive impairment (MCI) and prognostication, their use in the differential diagnosis of AD and their clinical application. As evidenced from the current literature, both amyloid and FDG-PET meet criteria for suitable biomarkers for the diagnosis of AD. They both indicate pathophysiological processes, albeit at different stages of the Alzheimer's process, and are distinct from normal patterns of aging. Conclusion: Both techniques have been shown to detect AD with high sensitivity and specificity compared to other neurodegenerative processes and cognitively normal age-matched individuals. However, future studies with standardised, uniform thresholds and a lengthier longitudinal follow-up need to be conducted to allow us to make surer conclusions about the future role of PET in clinical practice. In addition, comparison with post-mortem diagnosis, rather than clinical diagnosis with its acknowledged flaws, would result in more powerful statistical outcomes – which is becoming increasingly important given that several disease-modifying AD drugs are now in phase 3 trials.