Alberto Benussi1, Mario Grassi2, Fernando Palluzzi2, Giacomo Koch3,4, Vincenzo Di Lazzaro5, Raffaele Nardone6,7, Valentina Cantoni1, Valentina Dell'Era1, Enrico Premi1, Alessandro Martorana3,8, Francesco di Lorenzo3, Sonia Bonnì3, Federico Ranieri9, Fioravante Capone5, Gabriella Musumeci5, Maria Sofia Cotelli10, Alessandro Padovani1, Barbara Borroni1. 1. Department of Clinical and Experimental Sciences, Center for Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy. 2. Department of Brain and Behavioral Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, Italy. 3. Noninvasive Brain Stimulation Unit, Scientific Institute for Research, Hospitalisation and Health Care Santa Lucia Foundation, Rome, Italy. 4. Stroke Unit, Tor Vergata Polyclinic, Rome, Italy. 5. Unit of Neurology, Neurophysiology, and Neurobiology, Department of Medicine, Campus Bio-Medico University, Rome, Italy. 6. Department of Neurology, Franz Tappeiner Hospital, Merano, Italy. 7. Department of Neurology, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria. 8. Neurology Unit, Department of System Medicine, University of Tor Vergata, Rome, Italy. 9. Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy. 10. Neurology Unit, Vallecamonica Hospital, Esine, Italy.
Abstract
OBJECTIVE: Transcranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). METHODS: We performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5-fold cross-validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder. RESULTS: A total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86-0.92), high recall (0.93-0.98), and high F1 scores (0.89-0.95) in differentiating each neurodegenerative disorder. INTERPRETATION: TMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394-404.
OBJECTIVE: Transcranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). METHODS: We performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5-fold cross-validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder. RESULTS: A total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86-0.92), high recall (0.93-0.98), and high F1 scores (0.89-0.95) in differentiating each neurodegenerative disorder. INTERPRETATION: TMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394-404.
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