Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer’s disease (AD) Marcello Giordano a , Ligia J. Dominguez b , Teresa Vitrano a , Massimiliano Curatolo a , Anna Ferlisi b , Anna Di Prima b , Mario Belvedere b , Mario Barbagallo b, * a Alzheimer Center, Division of Geriatrics, Ospedale Ingrassia, ASP di Palermo, Palermo, Via La Loggia 5, 90100 Palermo, Italy b Geriatric Unit, Dipartimento di Medicina Clinica e Patologie Emergenti, University of Palermo, Viale F. Scaduto 6/c, 90144 Palermo, Italy 1. Introduction AD is a neurodegenerative disorder characterized by loss of memory and of other cognitive abilities. The neuropathological hallmark of the disease, known since 1907, is the presence of neurofibrillary tangles and senile (amyloid) plaques in brain regions serving memory and cognition, impaired synaptic func- tion, and cell loss (Selkoe, 2004). AD is one of the most important causes of severe disability in the older adults and represents a dramatic health problem, especially for its social and economic implications (Wimo and Winblad, 2001; Hebert et al., 2003). Although complete recovery is not an attainable goal, the improvement of the clinical picture (daily function, cognition, and behavioral disturbances), somatic symptoms, and quality of life (QoL) in the demented patients is an outcome that has been obtained with pharmacological and non-pharmacological approaches to some extent. Although other neurotransmitters may be involved, the loss of acetylcholine pathways occurs early and has been shown to correlate with the severity of memory impairment (Francis et al., 1999). Hence, the most widely used symptomatic drug treatment has focused on enhancing cholinergic neurotransmission (Cummings, 2004). Among non-pharmacological approaches, various methods attempted to compensate for cognitive deficit of AD patients by implementing memory training, use of memory aids, advice about the organization of routine daily activities, and ROT (Folsom, 1966; Wallis et al., 1983; Gerber et al., 1991; Zanetti et al., 1997; Spector et al., 2001). ROT was originally designed by Folsom (1966) to rehabilitate severely disturbed war veterans. It operates by means of the presentation of orientation information (i.e., time, place and person-related), which is thought to provide the person with a greater understanding of his/her surroundings, possibly resulting in an improved sense of control and self-esteem. ROT is one of the most commonly used cognitive rehabilitation approaches in patients with AD representing a relatively simple technique that can be performed by personnel without highly specialized training (Folsom, 1966; Spector et al., 2001). It is generally well accepted by the caregivers and relatives who may have the net feeling that it is doing something useful for the patient. Zanetti et al. (1995) demonstrated a significant improvement in MMSE score in subjects receiving ROT over 8.5 months, whereas the controls not receiving ROT had declining scores, confirming a net benefit of cognitive abilities in AD patients. A single-blind, multicenter, randomized controlled trial (RCT) of ROT in 201 AD patients Archives of Gerontology and Geriatrics 51 (2010) 245–249 ARTICLE INFO Article history: Received 9 June 2009 Received in revised form 8 November 2009 Accepted 10 November 2009 Available online 7 December 2009 Keywords: Dementia Alzheimer’s disease Donepezil Reality orientation therapy Cognitive rehabilitation ABSTRACT Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimer’s disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n = 100, mean age 78.4  4.3 years) initiated treatment with donepezil, 5 mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the training program, and after 2 months of follow-up. There was a significant improvement in mini-mental state examination (MMSE) score (p < 0.001) and the AD assessment scale-cognitive (ADAS-Cog) subscale (p < 0.001), without changes in impaired activity of daily living (ADL) and instrumental ADL (IADL) after intensive ROT training in Group A. MMSE was maintained after 2 months in-home ROT continuation. There were no significant changes in MMSE in drug- only treated patients (Group B) after 3 weeks, with a non-significant tendency to improvement in ADAS-Cog. Our results suggest benefit of an intensive ROT program in dementia patients receiving donepezil that seems to be maintained as far as ROT is continued by the caregiver. ß 2009 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +39 091 6552 885; fax: +39 091 6552 952. E-mail address: mabar@unipa.it (M. Barbagallo). Contents lists available at ScienceDirect Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger 0167-4943/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.archger.2009.11.008