Gemma Lombardi1, Cristina Polito2, Valentina Berti2, Camilla Ferrari3, Giulia Lucidi3,4, Silvia Bagnoli3, Irene Piaceri3, Benedetta Nacmias3, Alberto Pupi2, Sandro Sorbi3,4. 1. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, viale Pieraccini 6, 50139, Florence, Italy. glombardi@unifi.it. 2. Department of Biomedical, Experimental and Clinical Sciences "Mario Serio," Nuclear Medicine Unit, University of Florence, viale Morgagni 50, 50134, Florence, Italy. 3. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, viale Pieraccini 6, 50139, Florence, Italy. 4. IRCCS Don Gnocchi, via di Scandicci 269, 50143, Florence, Italy.
Abstract
BACKGROUND: An early differentiation between Alzheimer's Disease (AD) and other dementias is crucial for an adequate patients' management, albeit it may result difficult for the occurrence of "atypical presentations." Current diagnostic criteria recognize the importance of biomarkers for AD diagnosis, but still an optimal diagnostic work-up isn't available. OBJECTIVE: Evaluate the utility and reproducibility of biomarkers and propose an "optimal" diagnostic work-up in atypical dementia. METHODS: (1) a retrospective selection of "atypical dementia cases"; (2) a repetition of diagnostic assessment by two neurologists following two different diagnostic work-ups, each consisting of multiple steps; (3) a comparison between diagnostic accuracy and confidence reached at each step by both neurologists and evaluation of the inter-rater agreement. RESULTS: In AD, regardless of the undertaken diagnostic work-up, a significant gain in accuracy was reached by both neurologists after the second step, whereas in frontotemporal dementia (FTD), adding subsequent steps was not always sufficient to increase significantly the baseline accuracy. A relevant increment in diagnostic confidence was detectable after studying pathophysiological markers in AD, and after assessing brain metabolism in FTD. The inter-rater agreement was higher at the second step for the AD group when the pathophysiological markers were available and for the FTD group when the results of FDG-PET were accessible. CONCLUSIONS: In atypical cases of dementia, biomarkers significantly raise diagnostic accuracy, confidence, and agreement. This study introduces a proof of diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct ways to proceed on the basis of a greater diagnostic likelihood.
BACKGROUND: An early differentiation between Alzheimer's Disease (AD) and other dementias is crucial for an adequate patients' management, albeit it may result difficult for the occurrence of "atypical presentations." Current diagnostic criteria recognize the importance of biomarkers for AD diagnosis, but still an optimal diagnostic work-up isn't available. OBJECTIVE: Evaluate the utility and reproducibility of biomarkers and propose an "optimal" diagnostic work-up in atypical dementia. METHODS: (1) a retrospective selection of "atypical dementia cases"; (2) a repetition of diagnostic assessment by two neurologists following two different diagnostic work-ups, each consisting of multiple steps; (3) a comparison between diagnostic accuracy and confidence reached at each step by both neurologists and evaluation of the inter-rater agreement. RESULTS: In AD, regardless of the undertaken diagnostic work-up, a significant gain in accuracy was reached by both neurologists after the second step, whereas in frontotemporal dementia (FTD), adding subsequent steps was not always sufficient to increase significantly the baseline accuracy. A relevant increment in diagnostic confidence was detectable after studying pathophysiological markers in AD, and after assessing brain metabolism in FTD. The inter-rater agreement was higher at the second step for the AD group when the pathophysiological markers were available and for the FTD group when the results of FDG-PET were accessible. CONCLUSIONS: In atypical cases of dementia, biomarkers significantly raise diagnostic accuracy, confidence, and agreement. This study introduces a proof of diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct ways to proceed on the basis of a greater diagnostic likelihood.
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Authors: Sebastiaan Engelborghs; Ellis Niemantsverdriet; Hanne Struyfs; Kaj Blennow; Raf Brouns; Manuel Comabella; Irena Dujmovic; Wiesje van der Flier; Lutz Frölich; Daniela Galimberti; Sharmilee Gnanapavan; Bernhard Hemmer; Erik Hoff; Jakub Hort; Ellen Iacobaeus; Martin Ingelsson; Frank Jan de Jong; Michael Jonsson; Michael Khalil; Jens Kuhle; Alberto Lleó; Alexandre de Mendonça; José Luis Molinuevo; Guy Nagels; Claire Paquet; Lucilla Parnetti; Gerwin Roks; Pedro Rosa-Neto; Philip Scheltens; Constance Skårsgard; Erik Stomrud; Hayrettin Tumani; Pieter Jelle Visser; Anders Wallin; Bengt Winblad; Henrik Zetterberg; Flora Duits; Charlotte E Teunissen Journal: Alzheimers Dement (Amst) Date: 2017-05-18
Authors: Xiao Da; Jon B Toledo; Jarcy Zee; David A Wolk; Sharon X Xie; Yangming Ou; Amanda Shacklett; Paraskevi Parmpi; Leslie Shaw; John Q Trojanowski; Christos Davatzikos Journal: Neuroimage Clin Date: 2013-11-28 Impact factor: 4.881