Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review

Background: A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC). Objective: The purpose of this study was to determine the effects of CC as adjunct therapy to cholinesterase inhibitors (AChEI) in the treatment of AD. Methods: We identified relevant studies by electronic search until April 2020. We considered studies with a comparator group that enrolled elderly patients with a diagnosis of AD and employed CC as an adjunct therapy to AChEIs compared to AChEI monotherapy or comparisons of different AChEIs combined with CC. Methodological quality assessment was done using the Newcastle-Ottawa Scale. Results: Out of 149 articles identified, two retrospective cohort studies involving 563 elderly patients affected with AD were included. After 3 months and 9 months, better Mini-Mental Status Examination scores were observed in the AChEIs + CC group versus AChEIs alone group. CC combined with donepezil may be better in improving cognition than when combined with rivastigmine. No significant difference was noted in terms of activities of daily living (ADL) and instrumental-ADL. Neuropsychiatric Inventory and Geriatric Depression Scale-short form scores appeared to be lower in the combination treatment versus monotherapy. The adverse events of combined treatment were self-limiting and included occasional excitability, gastric intolerance, and headache. Conclusion: Limited evidence from pooled data of two observational studies suggests that CC used in adjunct with AChEIs in the treatment of AD was well-tolerated and showed improvement in cognition, mood, and behavioral symptoms compared to treating with AChEIs alone.