title: The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives.
abstract: BACKGROUND
  Citicoline is able to potentiate neuroplasticity and is a natural precursor of phospholipid synthesis, or rather serves as a choline source in the metabolic pathways for biosynthesis of acetylcholine. Several studies have shown that it can have beneficial effects both in degenerative and in vascular cognitive decline. The aim of the present study was to review the pharmacokinetics and pharmacodynamics of this drug and its role in cognitive impairment according to the present medical literature.
  
  
  METHODS
  A MEDLINE(®) search was made using the following key words: citicoline, pharmacokinetics, pharmacodynamics, elderly, cognitive impairment, vascular dementia, and Alzheimer's disease. Recent studies on the possible role of citicoline in increasing sirtuin 1 (SIRT1) expression were assessed. Some personal studies were also considered, such as the VITA study and the IDEALE study.
  
  
  RESULTS
  Administered by both oral and intravenous routes, citicoline is converted into two major circulating metabolites, cytidine and choline. It is metabolized in the gut wall and liver. Pharmacokinetic studies suggested that it is well absorbed and highly bioavailable with oral dosing. A number of studies have clearly shown the possible role of citicoline in cognitive impairment of diverse etiology. It can also modulate the activity/expression of some protein kinases involved in neuronal death and increases SIRT1 expression in the central nervous system. The VITA study and the IDEALE study suggested that both parenteral and oral citicoline are effective and safe. Other studies have clearly demonstrated citicoline's effects on several cognitive domains. Conversely, some studies did not point out any evidence of efficacy of this drug.
  
  
  CONCLUSIONS
  Citicoline appears to be a promising agent to improve cognitive impairment, especially of vascular origin. In fact, so far it appears as a drug with the ability to promote "safe" neuroprotection, capable of enhancing endogenous protective. Large clinical trials are needed to confirm its benefits.
authors.affiliation: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme, Catanzaro, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Gareri
authors.affiliation: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme, Catanzaro, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Castagna
authors.affiliation: ASL2 Turin, Turin, Italy.
authors.forename: Antonino Maria
authors.initials: AM
authors.lastname: Cotroneo
authors.affiliation: Elderly Assistance Unit, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Putignano
authors.affiliation: Department of Health Sciences, School of Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme, Catanzaro, Italy.
authors.forename: Amalia Cecilia
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D003072:Cognition Disorders / Q000188:drug therapy*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D006801:Humans; D018697:Nootropic Agents / Q000494:pharmacology*
chemical_list: D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline
keywords: citicoline; cognitive impairment; elderly; neurodegeneration; neuroprotective effects; sirtuins