A Atri, J Molinuevo, and D Wilkinson did not receive financial support or remuneration related to work on this study or manuscript. Authors’ contributions OL, YW and IP performed the analyses of the data and reviewed the manuscript. AA, JM and DW provided the interpretation and discussion of the data analyses outcome. All authors contributed to manuscript together preparation, and read and approved the final manuscript. Acknowledgements The reported analyses were made by H Lundbeck A/S, Denmark, in collaboration with Merz Pharmaceuticals GmbH, Germany. The original studies included in the present analysis were supported by funding from Forest Laboratories, Inc., New York. The authors would like to acknowledge the invaluable contribution of the principal investigators in the original trials as listed previously [16,17].

This manuscript was written with the assistance of Cambridge Medical Communication Ltd, and was funded by H. Lundbeck A/S, Denmark. While Dr Atri is the Associate Director, Clinical Operations, GRECC, ENRM Bedford VA Hospital, the contents of this study do not represent the views of the Department of Veterans Affairs or the United States Government. Finally, and most importantly, we express our deep gratitude for the commitment of the study participants and their caregivers, without whose generous contribution and dedication this research would not be possible.
The leading etiological hypothesis of Alzheimer’s disease (AD) points to excessive brain ??-amyloid (A??) that aggregates to form extracellular plaques and vascular wall deposits [1].

With increasing prevalence and associated cost of care and the likelihood of greater benefit if therapies are applied early, earlier and more accurate identification of AD has become a research priority. Dementia is usually preceded by a transition period of cognitive decline commonly referred to as mild cognitive impairment (MCI). Characterized by an objective impairment of memory and/or other cognitive domains, MCI is not severe enough to significantly interfere with activities of daily living [2]. The prevalence of MCI in people aged 65 is believed to be 10 to 20%, with over 10% who have been classified as MCI converting to dementia per year [3]. Histopathologic studies on brains of MCI subjects have shown characteristic AD pathology including A?? plaques and neurofibillary tangles in the majority of cases [4].

MCI has been further classified based on whether memory has been affected (amnestic MCI) or spared (nonamnestic MCI), GSK-3 and whether the cognitive deficit affected is mainly in one cognitive domain (single-domain MCI) or more than one domain (multidomain MCI). Hence, MCI can be classified into four clinical subtypes: nonamnestic single-domain, nonamnestic multiple domains, amnestic single-domain mostly (asMCI), and amnestic multiple domains (amMCI). These subtypes probably differ in etiology and outcome.