摘要：

OBJECTIVE: Aim of this study was to validate new diagnostic criteria, assessing and comparing diagnostic performance of individual criteria in patients with Mild Cognitive Impairment (MCI) coming from 3 European memory clinics. BACKGROUND: The availability of in vivo biomarkers of Alzheimer9s Disease (AD) neuropathology has led to the development of new diagnostic criteria that reconceptualize AD as a disease featuring the combination of brain amyloidosis and neurodegeneration beyond a core of clinical symptoms. DESIGN/METHODS: Markers of amyloidosis (abnormal CSF Abeta42) and neurodegeneration (hippocampal atrophy, TP hypometabolism on FDG PET, and abnormal CSF tau) were measured in 73 MCI patients clinically followed for at least 1 year (mean of 28±17 months) to ascertain progression to AD. Positive (LR+) and negative likelihood ratios (LR-) of individual items of IWG and NIA-AA criteria were compared. RESULTS: 29 MCI patients progressed to AD (pMCI) and 44 remained stable (sMCI). Among IWG criteria, positivity to any biomarker had lowest LR- (0.00), while positivity to FDGPET had highest LR+ (5.82) and low LR- (0.24) (IWG criteria). Among NIA-AA criteria, positivity to neurodegeneration (FDG-PET, MRI or CSF tau markers, irrespective of amyloidosis status) had lowest LR- (0.06), while positivity to AB42 and FDGPET or AB42 and hippocampal volume atrophy had highest LR+ (6.45 and 5.56). CONCLUSIONS: Markers of neurodegeneration are the strongest positive and negative predictors of short term incident dementia in MCI, irrespective of amyloidosis status. FDG-PET is the strongest individual positive predictive biomarker. Supported by: The Swedish Research Council Council (project 05817), the Strategic Research Program in Neuroscience at Karolinska Institutet, the Swedish Brain Power. This work was also supported by the grants: sottoprogetto finalizzato Strategico 2006: 99Strumenti e procedure diagnostiche per le demenze utilizzabili nella clinica ai fini della diagnosi precoce e differenziale, della individuazione delle forme a rapida o lenta progressione e delle forme con risposta ottimale alle attuali terapie99; Programma Strategico 2006, Convenzione 71; Programma Strategico 2007, Convenzione PS39, Ricerca Corrente Italian Ministry of Health. Some of the costs related to patient assessment and imaging and biomarker detection were paid by an ad hoc grant from the Fitness e Solidarieta9 2006 and 2007 campaigns. Disclosure: Dr. Frisoni has received personal compensation for activities with Eli Lilly & Company, Bristol-Myers Squibb Company, Bayer, Lundbeck, Elan Corporation, AstraZeneca Corporation, Pfizer Inc, Taurx, Wyeth Pharmaceuticals, and GE. Dr. Frisoni has recieved personal compensation in an editorial capacity for Lancet Neurology, Aging Clinical & Experimental Research, Alzheimer9s Diseases & Associated Disorders, Neurodegenerative Diseases, and Neurobiology of Aging. Dr. Frisoni has received research support from Wyeth Pharmaceuticals, Eli Lilly & Company, Lundbeck, GE, Avid/Lilly, and the Alzheimer9s Association. Dr. Prestia has nothing to disclose. Dr. Caroli has nothing to disclose. Dr. Nordberg hasreceived personal compensation for activities with Novartis. Dr. Scheltens has received personal compensation for serving on the Advisory board of Danone research, Wyeth-Elan, Lundbeck, Genentech, Pfizer, Quintiles.

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