A Retrospective Study on the Benefits of Combined Citicoline, Memantine, and Acetylcholinesterase Inhibitor Treatments in Older Patients Affected with Alzheimer's Disease

Background: Citicoline has been proven to have beneficial effects in patients with cognitive impairment. In previous studies, combined treatment with memantine and acetylcholinesterase inhibitors (AChEIs) maintained cognitive function in patients with Alzheimer's disease (AD) better than memantine or AChEIs alone. Objective: To evaluate the effectiveness and safety of a combination therapy of oral citicoline, memantine, and an AChEI in AD when compared with memantine and an AChEI without citicoline. Methods: This was a retrospective multi-centric case-control study, conducted in Italian Centers for Cognitive Impairment and Dementia. Overall, 170 patients were recruited (34.11% of men, mean age 76,81 +/- 4.93 years): 48.8% treated with memantine and donepezil; 48.2% with memantine and rivastigmine; 2.9% with memantine and galantamine. 89 patients (control-group) were treated with memantine and an AChEI, whereas 81 patients (case-group) were treated with oral citicoline 1000 mg/day added to memantine and an AChEI given orally. Cognitive functions, activities of daily living, instrumental activities of daily living, comorbidities, mood and behavioral disturbances were assessed at baseline, month 6, and month 12. Results: In the case group, MMSE score had a statistically significant increasing trend between T0 and T2 (14.88 +/- 2.95 versus 15.09 +/- 3.00; p = 0.040), whereas in the control group, MMSE score showed a statistically significant decrease trend (14.37 +/- 2.63 versus 14.03 +/- 2.92 p = 0.024). Conclusion: In older patients with AD, a triple therapy with citicoline, memantine, and AChEI was more effective than memantine and AChEI without citicoline in maintaining the MMSE total score after 12 months.