Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.
The use of Alzheimer's disease (AD) biomarkers is supported in diagnostic criteria, but their maturity for clinical routine is still debated. Here, we evaluate brain fluorodeoxyglucose positron emission tomography (FDG PET), a measure of cerebral glucose metabolism, as a biomarker to identify clinical and prodromal AD according to the framework suggested for biomarkers in oncology, using homogenous criteria with other biomarkers addressed in parallel reviews. FDG PET has fully achieved phase 1 (rational for use) and most of phase 2 (ability to discriminate AD subjects from healthy controls or other forms of dementia) aims. Phase 3 aims (early detection ability) are partly achieved. Phase 4 studies (routine use in prodromal patients) are ongoing, and only preliminary results can be extrapolated from retrospective observations. Phase 5 studies (quantify impact and costs) have not been performed. The results of this study show that specific efforts are needed to complete phase 3 evidence, in particular comparing and combining FDG PET with other biomarkers, and to properly design phase 4 prospective studies as a basis for phase 5 evaluations.
Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, University Hospitals of Geneva, Geneva University, Geneva, Switzerland. Electronic address: valentina.garibotto@gmail.com.
Valentina
V
Garibotto
Wolfson Molecular Imaging Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Karl
K
Herholz
Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; LANVIE (Laboratory of Neuroimaging of Aging), Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Marina
M
Boccardi
LANVIE (Laboratory of Neuroimaging of Aging), Department of Psychiatry, University of Geneva, Geneva, Switzerland; Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
Agnese
A
Picco
Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Andrea
A
Varrone
Department of Geriatric Medicine, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Agneta
A
Nordberg
Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
Flavio
F
Nobili
Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, University Hospitals of Geneva, Geneva University, Geneva, Switzerland.
Osman
O
Ratib
D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D003704:Dementia / Q000000981:diagnostic imaging; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results
D015415:Biomarkers; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
5-Phases; Alzheimer's disease; Biomarker-based diagnosis; Biomarkers development; Early diagnosis; FDG PET