CSF p-tau/Aβ42 ratio and brain FDG-PET may reliably detect MCI “imminent” converters to AD

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 (CS...

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Published in:European journal of nuclear medicine and molecular imaging 2020-12, Vol.47 (13), p.3152-3164
Main Authors: Santangelo, Roberto, Masserini, Federico, Agosta, Federica, Sala, Arianna, Caminiti, Silvia P., Cecchetti, Giordano, Caso, Francesca, Martinelli, Vittorio, Pinto, Patrizia, Passerini, Gabriella, Perani, Daniela, Magnani, Giuseppe, Filippi, Massimo
Format: Article
Language:English
Subjects:
Algorithms
Alzheimer's disease
Biomarkers
Brain
Cardiology
Cerebrospinal fluid
Cognitive ability
Conversion
Converters
Dementia
Dementia disorders
Diagnosis
Imaging
Medicine
Medicine & Public Health
Neurodegeneration
Neurodegenerative diseases
Neurology
Nuclear Medicine
Oncology
Original Article
Orthopedics
Positron emission
Positron emission tomography
Radiology
Regression analysis
Regression models
Tau protein
Tomography
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Summary: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.
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-020-04853-4