Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A beta species
Por:
Oliveira, F, Leuzy, A, Castelhano, J, Chiotis, K, Hasselbalch, SG, Rinne, J, Mendonca, A, Otto, M, Lleo, A, Santana, I, Johansson, J, Anderl-Straub, S, Arnim, C, Beer, A, Blesa, R, Fortea, J, Sanna-Kaisa, H, Portelius, E, Pannee, J, Zetterberg, H, Blennow, K, Moreira, AP, Abrunhosa, A, Nordberg, A, Castelo-Branco, M
Publicada:
1 ene 2018
Resumen:
Positron 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 beta (A beta) 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 A beta(38), A beta(40) and A beta(42) were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A beta 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 A beta 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. A beta(38) and A beta(40) 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 A beta(42), the A beta(42)/A beta(40) or A beta(42)/A beta(38) ratios were found compared to normalization based on cerebellar gray matter.
Filiaciones:
Oliveira, F:
Univ Coimbra, Fac Med, IBILI, CiBIT,ICNAS, Coimbra, Portugal
Leuzy, A:
Karolinska Inst, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Castelhano, J:
Univ Coimbra, Fac Med, IBILI, CiBIT,ICNAS, Coimbra, Portugal
Chiotis, K:
Karolinska Inst, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Hasselbalch, SG:
Univ Copenhagen, Rigshosp, Dept Neurol, Danish Dementia Res Ctr, Copenhagen, Denmark
Rinne, J:
Univ Turku, Turku Univ Hosp, Dept Clin Neurosci, Turku, Finland
Mendonca, A:
Univ Lisbon, Fac Med, Dept Neurol, Lisbon, Portugal
Univ Lisbon, Fac Med, Lab Neurosci, Lisbon, Portugal
Otto, M:
Univ Ulm, Dept Neurol, Ulm, Germany
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Santana, I:
Univ Coimbra, Ctr Hosp & Univ Coimbra, Fac Med, Neurol Dept, Coimbra, Portugal
Johansson, J:
Turku Univ Hosp, Turku PET Ctr, Turku, Finland
Anderl-Straub, S:
Univ Ulm, Dept Neurol, Ulm, Germany
Arnim, C:
Univ Ulm, Dept Neurol, Ulm, Germany
Beer, A:
Ulm Univ Hosp, Dept Nucl Med, Ulm, Germany
Blesa, R:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Sanna-Kaisa, H:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Portelius, E:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Pannee, J:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England
UK Dementia Res Inst, London, England
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Moreira, AP:
Univ Coimbra, Fac Med, IBILI, CiBIT,ICNAS, Coimbra, Portugal
Abrunhosa, A:
Univ Coimbra, Fac Med, IBILI, CiBIT,ICNAS, Coimbra, Portugal
Nordberg, A:
Karolinska Inst, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Castelo-Branco, M:
Univ Coimbra, Fac Med, IBILI, CiBIT,ICNAS, Coimbra, Portugal
Gold, Green Published
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