Application of Citicoline in Alzheimer's Disease

Alzheimer's disease is a progressive neurodegenerative disease characterized by memory loss, with lesions usually extending from specific limbic areas to the hippocampus, neocortex, and some subcortical nuclei. Thus loss of cholinergic neurons and subsequent acetylcholinease deficiency contribute to cognitive decline in AD patients.

Exogenous Citicoline can be used as an exogenous source of choline for the synthesis of acetylcholine, and the metabolism of citicoline and acetylcholine is shown in Figure 1. Animal experiments in recent years have shown that citicoline can increase the activity of acetylcholinesterase, increase the synthesis and/or release of acetylcholine, and improve memory impairment in rats.

Cholinesterase inhibitors (Acetylcholinesterase inhibitors, AChEIs) increase the content of acetylcholine in the synaptic cleft, and are currently the first-line treatment for mild to moderate Alzheimer's disease (Alzheimer's disease, AD).

1. Combination of citicoline and cholinesterase inhibitors in the treatment of Alzheimer's disease and mixed dementia

A retrospective, controlled study (The CITIRIVAD study) published in 2016 explored for the first time the effectiveness of the combination of citicoline and cholinesterase inhibitor rivastigmine in the treatment of 174 cases of AD and mixed dementia (mixed dementia, MD). sex and security.

The results confirmed that the combination of citicoline and rivastigmine is more effective than rivastigmine monotherapy in improving the cognitive function of AD/MD patients, delaying disease progression, and the drug safety is good.

2. Combination of citicoline and cholinesterase inhibitors in the treatment of Alzheimer's disease

A multi-center, retrospective, controlled study (The Citicholinage Study) published in 2017 further verified the efficacy of citicoline combined with cholinesterase inhibitors (including donepezil, rivastigmine, and galantamine) in the treatment of AD. Effectiveness and safety.

A total of 448 AD patients aged ≧65 consecutively enrolled in 7 centers in Italy were included in the study, divided into treatment group (AChEIs+ citicoline, citicoline 1000mg/d, p.o., 251 cases) and control group (AChEIs, 197 cases), the course of treatment was 9 months, and MMSE was used to evaluate cognition.

Cognitive function continued to deteriorate in patients receiving AChEIs alone through 9 months of treatment, while patients receiving AChEIs in combination with citicoline continued to improve cognitive function, and at 3 months of treatment, their cognitive function was significantly improved compared with patients using AChEIs alone (p=0.000) and remained until the end of treatment (p=0.000).

In addition, the study also compared the efficacy of citicoline combined with different AChEIs (donepezil, rivastigmine) in the treatment of cognitive impairment, and the results showed that donepezil combined with citicoline is more effective in the treatment of AD. This study confirmed that the combination of citicoline and AChEIs is more effective than AChEIs monotherapy in improving cognitive function and delaying disease progression in elderly AD patients.

In summary, the combination of citicoline and cholinesterase inhibitors in the treatment of patients with Alzheimer's disease is more effective in improving cognitive function and delaying disease progression than cholinesterase inhibitors alone. 

Tag: Citicoline , AD, choline

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