Research Article Comparison of Cognitive Rehabilitation versus Donepezil Therapy on Memory Performance, Attention, Quality of Life, and Depression among Multiple Sclerosis Patients Mohammad Mahdi Shahpouri , 1 Majid Barekatain , 2 Mahgol Tavakoli , 3 Omid Mirmosayyeb , 1 Ali Safaei , 1 and Vahid Shaygannejad 1 1 Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran 2 Department of Psychiatry, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 3 Department of Psychology, School of Educational Sciences and Psychology, University of Isfahan, Isfahan, Iran Correspondence should be addressed to Vahid Shaygannejad; v.shaygannejad@gmail.com Received 9 August 2020; Revised 29 September 2020; Accepted 7 November 2020; Published 23 November 2020 Academic Editor: Vincenzo Di Lazzaro Copyright © 2020 Mohammad Mahdi Shahpouri et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects cognitive performance and leads to depression and decreased quality of life (QOL). e current study aims to assess the effects of cognitive rehabilitation versus donepezil therapy on memory, attention, depression, and QOL in MS patients compared to placebo and control groups. Methods. Eighty MS patients were randomly selected from parallel randomized trials and divided into four groups: A: cognitive rehabilitation (10 sessions of 120 minutes), B: control (no intervention), C: donepezil (10mg daily), and D: placebo. Patients received the intervention for three months. ey were assessed for cognitive status, depression, and QOL prior to the intervention and immediately after that using abbreviated mental test (AMT), prospective and retrospective memory questionnaire (PRMQ), everyday memory questionnaire (EMQ), digit span, MSQOL-54, and second edition Beck depression inventory (BDI). We compared scores between groups after the intervention, as well as the progression of scores in every single group. Results. e cognitive rehabilitation group showed improvement in EMQ, RPMQ, digit span, physical and mental health subscales of MSQOL54, and depression (P < 0.05). We observed the same effect for donepezil except for the digit span test (P � 0.15). Intergroup comparison of scores showed the superiority of cognitive rehabilitation over donepezil in digit span, depression, and mental health scores. Conclusion. Both donepezil and cognitive rehabilitation effectively improve memory performance, attention, depression, and QOL in MS patients. Cognitive rehabilitation is superior altogether. is study is registered with the Iranian registry of clinical trials http://clinicaltrials.gov/ct2/show/IRCT2016042227522N1. 1. Introduction Multiple sclerosis (MS) is a chronic demyelinating inflam- matory disease that involves the central nervous system (CNS) and leads to the formation of focal lesions [1]. MS predominantly occurs in young females and causes a variety of physical, mental, and psychological disturbances that affect patients’ life considerably [2, 3]. Memory, attention, performance, and processing speed are among the affected cognitive areas [4]. ese disturbances added to the chronic nature of MS and patients’ impaired motor function pose depression in affected individuals [5, 6]. Altogether, the patients’ social, individual, and occupational lives will be affected and their quality of life (QOL) will get deteriorated [7]. Pharmacological interventions to improve cognitive impairment in MS patients are hardly investigated with conflicting findings. Donepezil, an acetylcholine esterase inhibitor (AChEI), is a neuroprotective drug used widely in the treatment of Alzheimer’s Disease [8]. Moreover, it is an agonist of sigma receptors that can be used in the treatment of cognitive impairment [9]. Donepezil therapy has been Hindawi Neurology Research International Volume 2020, Article ID 8874424, 8 pages https://doi.org/10.1155/2020/8874424