Abbreviations ARBD: alcohol-related brain damage; ARD: alcohol-related dementia; DSM-IV: Diagnostic and Statistical choose size Manual of Mental Disorders: 4th edition; EFNS: European Federation of Neurological Societies; KS: Korsakoff syndrome; WE: Wernicke’s encephalopathy; WKS: Wernicke-Korsakoff syndrome. Competing interests The authors declare that they have no competing interests.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which patients typically lose cognitive faculties, struggle to carry out activities of daily living (ADLs), and experience behavioural and neuropsychiatric problems. At present, AD cannot be cured, any improvements produced by pharmacotherapy are often temporary, and no treatments have been demonstrated to be disease-modifying.

Consequently, alleviating symptoms, and delaying or reducing clinical worsening (that is, symptom progression), without modifying the underlying pathophysiology, are realistic and meaningful treatment goals [1] that can be termed disease-course-modifying effects [2]. Achieving these goals allows patients to spend more time in the milder, more functional, stages of AD than they would without treatment [1]. Memantine, an uncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors, is approved in the EU and US for the treatment of patients with moderate to severe AD (Mini-Mental State Examination [MMSE] [3] score < 20). Donepezil, Dacomitinib a cholinesterase inhibitor (ChEI), is approved for the treatment of mild to moderate AD in the EU, and for mild, moderate, and severe AD in the US and some other countries.

As monotherapy, both memantine and donepezil have demonstrated efficacy for treating the symptoms of AD within their respective approved inhibitor Brefeldin A indications [4-12]. In addition, the incidence of clinical worsening, as defined by concurrent deterioration in three domains (cognitive, functional, and global) over time, is reduced by memantine treatment in patients with moderate to severe AD [6], and by donepezil treatment in patients with mild to moderate AD [13]. Since memantine and donepezil have different and complementary mechanisms of action, together they potentially offer additional benefits to the patient [14]. Pharmacokinetic and pharmacodynamic data in healthy volunteers provided initial evidence that memantine and donepezil may be safely used in combination [15]. The addition of memantine to stable ChEI therapy has also been associated with a good safety profile in patients with AD [16,17]. Two 24-week, randomised, double-blind, placebo-controlled trials (RCTs) have investigated the efficacy and safety of memantine 20 mg/day in combination with a ChEI.