Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting.
OBJECTIVE
The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI).


METHODS
We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression.


RESULTS
Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease.


CONCLUSIONS
In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy. perani.daniela@hsr.it.|Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy. perani.daniela@hsr.it.|Nuclear Medicine Unit, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy. perani.daniela@hsr.it.
Daniela
D
Perani
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.|Clinical Neuroscience Department, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Chiara
C
Cerami
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
Silvia Paola
SP
Caminiti
Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Roberto
R
Santangelo
Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Elisabetta
E
Coppi
Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Laura
L
Ferrari
Department of Neurology, Papa Giovanni XXIII Hospital, Piazza OMS, 1, 24127, Bergamo, Italy.
Patrizia
P
Pinto
Servizio di Medicina di Laboratorio OSR, Via Olgettina, 60, 20132, Milan, Italy.
Gabriella
G
Passerini
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.|CERMAC - Department of Neuroradiology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Andrea
A
Falini
Clinical Neuroscience Department, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Sandro
S
Iannaccone
Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.|IUSS Pavia, Piazza della Vittoria, 15, 27100, Pavia, Italy.
Stefano Francesco
SF
Cappa
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy.|Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Giancarlo
G
Comi
Nuclear Medicine Unit, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.
Luigi
L
Gianolli
Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy. magnani.giuseppe@hsr.it.
Giuseppe
G
Magnani
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000175:diagnosis; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18
Alzheimer’s Disease; Biomarkers; Clinical setting; Dementia diagnosis; Mild Cognitive Impairment