Improved Risk Stratification for Progression from Mild Cognitive Impairment to Alzheimer’s Disease with a Multi-Analytical Evaluation of Amyloid-β Positron Emission Tomography

Article type: Research Article

Authors: Beyer, Leonie^a | Brendel, Matthias^{a; *} | Scheiwein, Franziska^a | Sauerbeck, Julia^a | Hosakawa, Chisa^b | Alberts, Ian^c | Shi, Kuangyu^c | Bartenstein, Peter^a | Ishii, Kazunari^b | Seibyl, John^d | Cumming, Paul^{c; e} | Rominger, Axel^c | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Nuclear Medicine, University Hospital of Munich, LMU, Munich, Germany | [b] Department of Radiology, Kindai University, Osaka, Japan | [c] Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland | [d] Invicro, New Haven, CT, USA | [e] School of Psychology and Counseling and IHBI, Queensland University of Technology, Brisbane, Australia

Correspondence: [] Correspondence to: Matthias Brendel, MD, Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, Marchioninistr. 15, 81377 München, Germany. Tel.: +49 89 4400 74650; E-mail: Matthias.Brendel@med.uni-muenchen.de.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Amyloid-β (Aβ) accumulation in brain of patients with suspected Alzheimer’s disease (AD) can be assessed by positron emission tomography (PET) in vivo. While visual classification prevails in the clinical routine, semiquantitative PET analyses may enable more reliable evaluation of cases with a visually uncertain, borderline Aβ accumulation. Objective:We evaluated different analysis approaches (visual/semiquantitative) to find the most accurate and sensitive interpretation of Aβ-PET for predicting risk of progression from mild cognitive impairment (MCI) to AD. Methods:Based on standard uptake value (SUV) ratios of a cortical-composite volume of interest of 18F-AV45-PET from MCI subjects (n = 396, ADNI database), we compared three different reference region (cerebellar grey matter, CBL; brainstem, BST; white matter, WM) normalizations and the visual read by receiver operator characteristics for calculating a hazard ratio (HR) for progression to Alzheimer’s disease dementia (ADD). Results:During a mean follow-up time of 45.6±13.0 months, 28% of the MCI cases (110/396) converted to ADD. Among the tested methods, the WM reference showed best discriminatory power and progression-risk stratification (HRWM of 4.4 [2.6–7.6]), but the combined results of the visual and semiquantitative analysis with all three reference regions showed an even higher discriminatory power. Conclusion:A multi-analytical composite of visual and semiquantitative reference tissue analyses of 18F-AV45-PET gave improved risk stratification for progression from MCI to ADD relative to performance of single read-outs. This optimized approach is of special interest for prospective treatment trials, which demand a high accuracy.

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, dementia, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-190818

Journal: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 101-112, 2020