Contents lists available at ScienceDirect Psychiatry Research: Neuroimaging journal homepage: www.elsevier.com/locate/psychresns Predicting progression of amnesic MCI: The integration of episodic memory impairment with perfusion SPECT Davide Quaranta a, ⁎ , Guido Gainotti b,c , Daniela Di Giuda d , Maria Gabriella Vita a , Fabrizio Cocciolillo d , Giordano Lacidogna b , Valeria Guglielmi a , Carlo Masullo b , Alessandro Giordano d , Camillo Marra b a Neurology Unit, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy b Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy c IRCCS Fondazione Santa Lucia, Department of Clinical and Behavioral Neurology, Rome, Italy d Institute of Nuclear Medicine, Università Cattolica del Sacro Cuore, Rome, Italy ARTICLE INFO Keywords: Amnesic Mild Cognitive Impairment Alzheimer's Disease Episodic memory score Conversion to dementia 99 m Tc-HMPAO-SPECT hypoperfusion Posterior Cingulate Cortex ABSTRACT The present study aimed at assessing if the ability to predict progression from amnesic Mild Cognitive Impairment (aMCI) to dementia is improved by considering the presence at the baseline of Single Photon Emission Computed Tomography (SPECT) perfusion abnormalities in addition to a defect of long term memory. The Episodic Memory Score (EMS), a global index which integrates results obtained in subtests of the Rey's Verbal Learning Test and the Rey-Osterrieth Figure recall, were taken into account to evaluate defects of long term memory. The study sample consisted of 42 subjects affected by aMCI, who were followed-up during a two- year period. At the final follow-up 15 subjects progressed to AD. The EMS predicted progression from aMCI to dementia with a high level of sensitivity and a lower level of specificity, but the association of neuropsycho- logical (EMS) and SPECT data (hypoperfusion in the Posterior Cingulate Cortex) increased the accuracy in predicting conversion from aMCI to AD. The association of results obtained by aMCI patients on memory tests and perfusion SPECT may improve the accuracy in detecting subjects who will progress to dementia. The use of currently available and low-cost investigations could be advantageous in terms of public health policies. 1. Introduction The construct of mild cognitive impairment (MCI) was proposed by Petersen et al. (1999), drawing on a term previously suggested by Flicker et al. (1991), with the goal of identifying patients at risk of developing Alzheimer's Disease (AD) in their pre-clinical stage, using as reference the neuropathological and the neuropsychological staging of AD. In fact, Braak and Braak (1991) proposed a neuropathological progression of AD in which the first elementary lesions (and in parti- cular the neurofibrillary tangles) involved the entorhinal cortex and hippocampus, disconnecting the Papez circuit from information coming from the outside world through the entorhinal cortex. As this dis- connection hinders the formation of new episodic memories and as these disorders characterize the early stages of AD (Knopman and Ryberg, 1989; Welsh et al., 1991), long-term memory disorders were the hallmarks of the MCI construct, proposed by Petersen et al. (1999). However, when those simple clinical criteria were implemented in follow-up investigations, it became clear that only some MCI patients progress to dementia, whereas most of them do not convert to AD or another form of dementia, but remain stable or even revert to a normal stage (Dickerson et al., 2007; Koepsell and Monsell, 2012; Mitchell and Shiri-Feshki, 2009). The strategies followed to increase the capacity to predict conversion from MCI to AD have consisted in distinguishing different forms of MCI (Petersen, 2004; Winblad et al., 2004) (amnesic vs. non-amnesic and single-domain vs. multiple-domain), with the identification of the amnesic forms (aMCI) as those that more specifi- cally convert to AD (Petersen, 2004); in assessing the reliability of cognitive tests of delayed recall as reliable predictors of AD in in- dividuals with aMCI (Gainotti et al., 2014; Grober et al., 2000; Sarazin et al., 2007); and in taking into account a series of distinctive and re- liable biomarkers of AD, which allow to predict conversion from MCI to AD. The relations between specific forms of MCI (e. g. amnesic vs. non- amnesic and single-domain vs. multiple-domain) and the construct of ‘cognitive reserve’ have also been considered by some authors. Thus, Andrejeva et al. (2016) showed that the amnestic multiple-domain subtype is the most frequent one and suggested that a high cognitive https://doi.org/10.1016/j.pscychresns.2017.10.008 Received 30 May 2017; Received in revised form 18 September 2017; Accepted 23 October 2017 ⁎ Correspondence to: Neurology Unit, Fondazione Policlinico Universitario Agostino Gemelli, Largo Agostino Gemelli, 8, 00168 Rome, Italy. E-mail address: davide.quaranta@policlinicogemelli.it (D. Quaranta). Psychiatry Research: Neuroimaging xxx (xxxx) xxx–xxx 0925-4927/ © 2017 Elsevier B.V. All rights reserved. Please cite this article as: Quaranta, D., Psychiatry Research: Neuroimaging (2017), http://dx.doi.org/10.1016/j.pscychresns.2017.10.008