Matteo Cotta Ramusino1,2, Valentina Garibotto3,4, Ruggero Bacchin5,6, Daniele Altomare5, Alessandra Dodich3, Frederic Assal5, Aline Mendes5, Alfredo Costa7, Michele Tinazzi6, Silvia D Morbelli8, Matteo Bauckneht8, Agnese Picco9, Massimo E Dottorini10, Cristina Tranfaglia10, Lucia Farotti11, Nicola Salvadori11, Davide Moretti12, Giordano Savelli13, Anna Tarallo14, Flavio Nobili9,15, Maura Parapini5, Carlo Cavaliere16, Elena Salvatore17, Marco Salvatore16, Marina Boccardi5,14, Giovanni B Frisoni5. 1. Memory Clinic and LANVIE -Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Chemin du Petit Bel-Air 2, Bâtiment Voirons, CH1225, Geneva, Switzerland. matteo.cottaramusino01@universitadipavia.it. 2. Center for Cognitive and Behavioral Disorders, IRCCS Mondino Foundation and Dept of Brain and Behavior, University of Pavia, 27100, Pavia, Italy. matteo.cottaramusino01@universitadipavia.it. 3. NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, CH1205, Geneva, Switzerland. 4. Division of Nuclear Medicine, Geneva University Hospitals, CH1205, Geneva, Switzerland. 5. Memory Clinic and LANVIE -Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Chemin du Petit Bel-Air 2, Bâtiment Voirons, CH1225, Geneva, Switzerland. 6. Dept of Neurosciences, Biomedicine and Movement Sciences, Section of Neurology, University of Verona, 34134, Verona, Italy. 7. Center for Cognitive and Behavioral Disorders, IRCCS Mondino Foundation and Dept of Brain and Behavior, University of Pavia, 27100, Pavia, Italy. 8. Nuclear Medicine, Dept of Health Sciences (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, 16132, Genoa, Italy. 9. Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, 16126, Genoa, Italy. 10. Nuclear Medicine Division, "S. Maria della Misericordia" Hospital, 06129, Perugia, Italy. 11. Center for Memory Disturbances, Laboratory of Clinical Neurochemistry, University of Perugia, 06123, Perugia, Italy. 12. Alzheimer's Disease Operative Unit, IRCCS S, Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy. 13. Nuclear Medicine Division, Fondazione Poliambulanza Istituto Ospedaliero, 25124, Brescia, Italy. 14. LANE-Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS San Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy. 15. IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy. 16. IRCCS SDN, 80143, Naples, Italy. 17. University of Naples "Federico II", 80131, Naples, Italy.
Abstract
PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.
PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.
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