Journal of Alzheimer’s Disease 40 (2014) 737–742 DOI 10.3233/JAD-131154 IOS Press 737 Do Cholinesterase Inhibitors Act Primarily on Attention Deficit? A Naturalistic Study in Alzheimer’s Disease Patients Laura Bracco, Valentina Bessi, Sonia Padiglioni, Sandro Marini and Giancarlo Pepeu ∗ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy Handling Associate Editor: Benedetta Nacmias Accepted 18 December 2013 Abstract. Attention is the first non-memory domain affected in Alzheimer’s disease (AD), before deficits in language and visuo-spatial function, and it is claimed that attention deficits are responsible for the difficulties with daily living in early demented patients. The aim of this longitudinal study in a group of 121 Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State Examination (MMSE) score >17) was to detect which cognitive domains were most affected by the disease and whether one year treatment with cholinesterase inhibitors was more effective in preserving attention than memory. All subjects were evaluated by a neuropsychological battery including global measurements (MMSE, Information-Memory- Concentration Test) and tasks exploring verbal long-term memory, language, attention, and executive functions. The comparison between two evaluations, made 12 months apart, shows statistically significant differences, indicating deterioration compared to baseline, in the following tests: MMSE (with no gender differences), Composite Memory Score, Short Story Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test. Conversely, there were no differences in the two evaluations of the Digit Span, Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It appears that the treatment specifically attenuated the decline in tests assessing attention and executive functions. A stabilization of the ability to pay attention, with the ensuing positive effects on executive functions, recent memory, and information acquisition which depend on attention, appears to be the main neuropsychological mechanism through which the activation of the cholinergic system, resulting from cholinesterase inhibition, exerts its effect on cognition. Keywords: Acetylcholine, attention, cholinergic system, donepezil, galantamine, rivastigmine INTRODUCTION Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive deficits including memory [1] and attention [2, 3]. Attention is the cognitive process of focusing on one aspect of the environment while ignoring others and is the key to successful encoding of information [4]. Atten- tion is the first non-memory domain to be affected ∗ Correspondence to: Giancarlo Pepeu, Division of Pharmacol- ogy, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Pieraccini 6, 50139 Flo- rence, Italy. Tel.: +39 0554271274; Fax: +39 4271280; E-mail: giancarlo.pepeu@unifi.it. in AD, before deficits in language and visuo-spatial function, and attention deficits are responsible for the difficulties with daily living which early demented patients experience [2, 5]. Baddeley et al. [6] con- firmed that attentional control of executive function declines during the early stages of AD and observed that dual-task performances are particularly affected, as demonstrated by computerized attention tests [7]. Impaired attention can be detected in AD preclini- cal stages and in mild cognitive impairment (MCI), and it has been shown that attentional control deficits increase in the MCI/AD continuum [8]. Much evidence from animal and clinical investigations demonstrates the role and importance of the forebrain cholinergic ISSN 1387-2877/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved