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dc.contributor.authorOliveira, Francisco-
dc.contributor.authorLeuzy, Antoine-
dc.contributor.authorCastelhano, J.-
dc.contributor.authorChiotis, Konstantinos-
dc.contributor.authorHasselbalch, Steen Gregers-
dc.contributor.authorRinne, Juha-
dc.contributor.authorMendonça, Alexandre de-
dc.contributor.authorOtto, Markus-
dc.contributor.authorLleó, Alberto-
dc.contributor.authorSantana, Isabel-
dc.contributor.authorJohansson, Jarkko-
dc.contributor.authorAnderl-Straub, Sarah-
dc.contributor.authorArnim, Christine-
dc.contributor.authorBeer, Ambros-
dc.contributor.authorBlesa, Rafael-
dc.contributor.authorFortea, Juan-
dc.contributor.authorSanna-Kaisa, Herukka-
dc.contributor.authorPortelius, Erik-
dc.contributor.authorPannee, Josef-
dc.contributor.authorZetterberg, Henrik-
dc.contributor.authorBlennow, Kaj-
dc.contributor.authorMoreira, Ana P.-
dc.contributor.authorAbrunhosa, Antero-
dc.contributor.authorNordberg, Agneta-
dc.contributor.authorCastelo-Branco, Miguel-
dc.description.abstractPositron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid β (Aβ) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than Aβ concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. Aβ38 and Aβ40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray
dc.description.sponsorshipThis study was supported by the JPND networks BiomarkAPD (01ED1203F) and PreFrontAls (01ED1512), the German Federal Ministry of Education and Research (FTLDc O1GI1007A), FAIR-PARK II633190, the Foundation of the State Baden-Württemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009), Thierry Latran Foundation. This study was part of BIOMARKAPD, EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND ( Stockholm (A.L., K.C. and A.N.), the Swedish Research Council (projects 529-2012-14 and 05817), the Karolinska Institutet Strategic Neuroscience program, the Stockholm Country Council-Karolinska Institutet regional agreement on medical training and clinical research (ALF grant), Swedish Brain Power, the Swedish Brain Foundation, Swedish Alzheimer Foundation, Gun and Bertil Stohnes Foundation, Demensfonden, the Alzheimer Foundation in Sweden, the Foundation for Old Servants, the Swedish Foundation for Strategic Research (SSF), and the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n_ HEALTH-F2- 2011-278850 (INMiND); Gothenburg (E.P., J.P., H.Z., and K.B.) the Swedish Research Council (project 529-2012-14), the Gamla Tjänarinnor foundation, ERC (681712), the Wolfson Foundation, the Knut and Alice Wallenberg Foundation, Frimurarestiftelsen and the Alzheimer Foundation, the Torsten Söderberg foundation, Hjärnfonden and the Swedish Alzheimer Foundation; Barcelona (A.Leo´, R.B. and J.F.), Instituto de Salud Carlos III (PI11/03035-BIOMARKAPD, PI11/ 02425 and PI14/01126, PI13/01532, PI14/01561), jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), European Union, ‘Una manera de hacer Europa’ and ‘Marato´ TV3’ grant 0142610; Turku (JOR and SKH), Academy of Finland (decision no. 263193), Sigrid Juselius Foundation, Turku University Hospital Clinical Grants; Ulm (M.O., S.A.S., C.A.F.V.A., and A.B.), BMBF (Ministry of Science and Technology): Competence net neurodegenerative dementias (project: FTLDc), the JPND networks for standardisation of biomarkers (SOPHIA) and the JPND project, PreFronals, the foundation of the state of Baden-Wuerttemberg and The Thierry Latran Foundation and BIU (Boehringer IngelheimUlm University BioCentre). Contract grant sponsor: “Projecto Operacional Regional do Centro”–BIGDATIMAGE; CENTRO-01-0145-FEDER-000016 and MEDPersystPOCI-01-0145- FEDER-016428; Contract grant sponsor: FCT; Contract grant number: UID/NEU/ 04539/2013; Contract grant sponsor: COMPETE; Contract grant number:
dc.subject.meshAlzheimer Diseasept
dc.subject.meshAmyloid beta-Peptidespt
dc.subject.meshCarbon Radioisotopespt
dc.subject.meshMiddle Agedpt
dc.subject.meshPositron-Emission Tomographypt
dc.subject.meshAniline Compoundspt
dc.subject.meshData Analysispt
dc.titleData driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of Aβ speciespt
degois.publication.titleNeuroImage: Clinicalpt
item.fulltextCom Texto completo-
item.openairetypearticle- - Center for Neuroscience and Cell Biology- - Center for Neuroscience and Cell Biology- - Institute for Nuclear Sciences Applied to Health- - Coimbra Institute for Biomedical Imaging and Translational Research-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D ICNAS - Artigos em Revistas Internacionais
I&D CIBIT - Artigos em Revistas Internacionais
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