Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting |
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Authors: | Daniela Perani Chiara Cerami Silvia Paola Caminiti Roberto Santangelo Elisabetta Coppi Laura Ferrari Patrizia Pinto Gabriella Passerini Andrea Falini Sandro Iannaccone Stefano Francesco Cappa Giancarlo Comi Luigi Gianolli Giuseppe Magnani |
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Institution: | 1.Vita-Salute San Raffaele University,Milan,Italy;2.Division of Neuroscience,San Raffaele Scientific Institute,Milan,Italy;3.Nuclear Medicine Unit,San Raffaele Hospital,Milan,Italy;4.Clinical Neuroscience Department,San Raffaele Hospital,Milan,Italy;5.Department of Neurology,San Raffaele Hospital,Milan,Italy;6.Department of Neurology,Papa Giovanni XXIII Hospital,Bergamo,Italy;7.Servizio di Medicina di Laboratorio OSR,Milan,Italy;8.CERMAC – Department of Neuroradiology,San Raffaele Hospital,Milan,Italy;9.IUSS Pavia,Pavia,Italy |
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Abstract: | PurposeThe 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).MethodsWe 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.ResultsDiagnosis 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.ConclusionIn 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. |
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