TY - JOUR
T1 - CSF p-tau/Aβ42 ratio and brain FDG-PET may reliably detect MCI “imminent” converters to AD
AU - Santangelo, Roberto
AU - Masserini, Federico
AU - Agosta, Federica
AU - Sala, Arianna
AU - Caminiti, Silvia P.
AU - Cecchetti, Giordano
AU - Caso, Francesca
AU - Martinelli, Vittorio
AU - Pinto, Patrizia
AU - Passerini, Gabriella
AU - Perani, Daniela
AU - Magnani, Giuseppe
AU - Filippi, Massimo
N1 - Funding Information:
This work was carried out within the framework of the Ivascomar project of the Italian Ministry of Research (CTN01_00177_165430), Cluster Tecnologico Nazionale Scienze della Vita “Alisei”, Italian Ministry of Research. The sponsor had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; and the decision to submit the article for publication.
Funding Information:
F Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Novartis and Philips; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Purpose: To know whether mild cognitive impairment (MCI) patients will develop Alzheimer’s disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker such as brain FDG-PET to define an objective algorithm, suitable not only to reliably detect MCI converters to AD dementia but also to predict timing of conversion. Methods: We included 77 consecutive MCI patients with neurological/neuropsychological assessment, brain 18F-FDG-PET and CSF analysis available at diagnosis and a neuropsychological/neurological evaluation every 6 months for a medium- to a long-term follow-up (at least 2 and up to 8 years). Binomial logistic regression models and Kaplan-Meier survival analyses were performed to determine the best biomarker (or combination of biomarkers) in detecting MCI converters to AD dementia and then, among the converters, those who converted in short time frames. Results: Thirty-five out of 77 MCI patients (45%) converted to AD dementia, with an average conversion time since MCI diagnosis of 26.07 months. CSF p-tau/Aβ42 was the most accurate predictor of conversion from MCI to AD dementia (82.9% sensitivity; 90% specificity). CSF p-tau/Aβ42 and FDG-PET-positive MCIs converted to AD dementia significantly earlier than the CSF-positive-only MCIs (median conversion time, 17.1 vs 31.3 months). Conclusions: CSF p-tau/Aβ42 ratio and brain FDG-PET may predict both occurrence and timing of MCI conversion to full-blown AD dementia. MCI patients with both biomarkers suggestive for AD will likely develop an AD dementia shortly, thus representing the ideal target for any new experimental drug requiring short periods to be tested for.
AB - Purpose: To know whether mild cognitive impairment (MCI) patients will develop Alzheimer’s disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker such as brain FDG-PET to define an objective algorithm, suitable not only to reliably detect MCI converters to AD dementia but also to predict timing of conversion. Methods: We included 77 consecutive MCI patients with neurological/neuropsychological assessment, brain 18F-FDG-PET and CSF analysis available at diagnosis and a neuropsychological/neurological evaluation every 6 months for a medium- to a long-term follow-up (at least 2 and up to 8 years). Binomial logistic regression models and Kaplan-Meier survival analyses were performed to determine the best biomarker (or combination of biomarkers) in detecting MCI converters to AD dementia and then, among the converters, those who converted in short time frames. Results: Thirty-five out of 77 MCI patients (45%) converted to AD dementia, with an average conversion time since MCI diagnosis of 26.07 months. CSF p-tau/Aβ42 was the most accurate predictor of conversion from MCI to AD dementia (82.9% sensitivity; 90% specificity). CSF p-tau/Aβ42 and FDG-PET-positive MCIs converted to AD dementia significantly earlier than the CSF-positive-only MCIs (median conversion time, 17.1 vs 31.3 months). Conclusions: CSF p-tau/Aβ42 ratio and brain FDG-PET may predict both occurrence and timing of MCI conversion to full-blown AD dementia. MCI patients with both biomarkers suggestive for AD will likely develop an AD dementia shortly, thus representing the ideal target for any new experimental drug requiring short periods to be tested for.
KW - Alzheimer’s disease
KW - Brain FDG-PET
KW - Cerebrospinal fluid biomarkers
KW - MCI (mild cognitive impairment)
KW - MCI converters to AD
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U2 - 10.1007/s00259-020-04853-4
DO - 10.1007/s00259-020-04853-4
M3 - Article
C2 - 32415550
AN - SCOPUS:85084790490
VL - 47
SP - 3152
EP - 3164
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 13
ER -