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A Cross-Validation of FDG- and Amyloid-PET Biomarkers in Mild Cognitive Impairment for the Risk Prediction to Dementia due to Alzheimer's Disease in a Clinical Setting
Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS San Raffaele Sci Inst, Div Neurosci, In Vivo Human Mol & Struct Neuroimaging Unit, Milan, Italy..
Karolinska Inst, Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Dept NVS, Stockholm, Sweden..
IRCCS San Raffaele Hosp, Nucl Med Unit, Milan, Italy.;San Raffaele G Giglio Inst, Nucl Med Unit, Dept Radiol Sci, Cefalu, Italy..
Karolinska Inst, Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Dept NVS, Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
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2017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 59, no 2, 603-614 p.Article in journal (Refereed) Published
Abstract [en]

Assessments of brain glucose metabolism (F-18-FDG-PET) and cerebral amyloid burden (C-11-PiB-PET) in mild cognitive impairment (MCI) have shown highly variable performances when adopted to predict progression to dementia due to Alzheimer's disease (ADD). This study investigates, in a clinical setting, the separate and combined values of F-18-FDGPET and C-11-PiB-PET in ADD conversion prediction with optimized data analysis procedures. Respectively, we investigate the accuracy of an optimized SPM analysis for F-18-FDG-PET and of standardized uptake value ratio semiquantification for C-11-PiB-PET in predicting ADD conversion in 30 MCI subjects (age 63.57 +/- 7.78 years). Fourteen subjects converted to ADD during the follow-up (median 26.5 months, inter-quartile range 30 months). Receiver operating characteristic analyses showed an area under the curve (AUC) of 0.89 and of 0.81 for, respectively, F-18-FDG-PET and C-11-PiB-PET. F-18-FDG-PET, compared to C-11-PiB-PET, showed higher specificity (1.00 versus 0.62, respectively), but lower sensitivity (0.79 versus 1.00). Combining the biomarkers improved classification accuracy (AUC = 0.96). During the follow-up time, all the MCI subjects positive for both PET biomarkers converted to ADD, whereas all the subjects negative for both remained stable. The difference in survival distributions was confirmed by a log-rank test (p = 0.002). These results indicate a very high accuracy in predicting MCI to ADD conversion of both F-18-FDG-PET and C-11-PiB-PET imaging, the former showing optimal performance based on the SPM optimized parametric assessment. Measures of brain glucose metabolism and amyloid load represent extremely powerful diagnostic and prognostic biomarkers with complementary roles in prodromal dementia phase, particularly when tailored to individual cases in clinical settings.

Place, publisher, year, edition, pages
2017. Vol. 59, no 2, 603-614 p.
Keyword [en]
Alzheimer's disease, C-11-PiB-PET, conversion prediction, dementia, early diagnosis, F-18-FDG-PET, mild cognitive impairment, prognosis
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-331961DOI: 10.3233/JAD-170158ISI: 000405805400019OAI: oai:DiVA.org:uu-331961DiVA: diva2:1151026
Funder
EU, FP7, Seventh Framework Programme, 278850, HEALTH-F2-2011278850Swedish Research Council, 05817Swedish Foundation for Strategic Research The Swedish Brain FoundationWenner-Gren Foundations
Available from: 2017-10-20 Created: 2017-10-20 Last updated: 2017-10-20Bibliographically approved

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