The CITIDEMAGE Study: Combined Treatment with a Cholinergic Precursor in Dementia Patients

Abstract

Certain previous studies have demonstrated the benefits of the addition of citicoline, a cholinergic precursor, to acetylcholinesterase inhibitors (AchEIs) or memantine in patients with Alzheimer’s disease (AD). The present study showed the effectiveness of oral citicoline plus AchEIs plus memantine in outpatients with AD. This was a retrospective case-control study involving 169 patients aged 65 years old or older having AD (mean age: 78.7 ±4.9 years). In addition, 84 patients were treated with AchEIs plus memantine plus citicoline 1 g/day given orally (group A), and 85 patients were treated with AchEIs plus memantine (group B). In both groups, memantine and AchEIs were used at the highest dosage tolerated. Tests were administered at baseline (T0), after 6 (T1), and 12 months (T2) and included MMSE, ADL, IADL, NPI, CIRS, GDS-short form, the EuroQoL, and the Sleep questionnaire. The primary outcomes were the effects of combined treatment versus AchEIs plus memantine on cognitive functions assessed by MMSE. The secondary outcomes were possible side effects of treatment in both groups, the influence on daily life functions, behavioral symptoms, quality of life, and sleep. Patients in group A showed a mild increase in MMSE at 6 (15.85 ±2.86 vs. 16.39 ±2.93) and 12 months (16.39 ±2.93 vs. 16.43 ±3.08). On comparing the two groups, the difference in MMSE score was significant, both at T1 (p = 0.003) and T2 (p = 0.011). Moreover, a significant improvement in GDS and EuroQoL scores was observed. No differences in secondary outcomes, including side effects, were observed between the two groups. This study strengthens the role of citicoline plus AchEIs plus memantine in patients with AD.