Search

Pietro Gareri,1 Alberto Castagna,1 Antonino Maria Cotroneo,2 Salvatore Putignano,3 Giovambattista De Sarro,4 Amalia Cecilia Bruni11Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme, Catanzaro, 2ASL2 Turin, Turin, 3Elderly Assistance Unit, Naples, 4Department of Health Sciences, School of Medicine, University Magna Græcia of Catanzaro, Catanzaro, ItalyBackground: 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.Conclusion: 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.Keywords: citicoline, cognitive impairment, elderly, neurodegeneration, neuroprotective effects, sirtuinsCorrigendum for this paper has been published

Antonino Maria Cotroneo,1 Alberto Castagna,2 Salvatore Putignano,3 Roberto Lacava,2 Fausto Fantò,4 Francesco Monteleone,5 Filomena Rocca,2 Alba Malara,6 Pietro Gareri21ASL 2 Turin, Piedmont, 2Elderly Health Care, Ambulatory Center for Dementia, ASP Catanzaro, Calabria, 3ASL Napoli 1, Campania, 4University Hospital Orbassano, Turin, Piedmont, 5Regina Margherita Hospital, Rome, 6Nursing Home S Domenico Lamezia Terme, ASP Catanzaro, Calabria, ItalyBackground: The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment.Methods: The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67–90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study.Results: MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded.Conclusion: In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.Keywords: citicoline, vascular mild cognitive impairment, elderly, safety, effectiveness

Salvatore Putignano, Pietro Gareri, Alberto Castagna, Giuliano Cerqua, Pasquale Cervera, Antonino Maria Cotroneo, Francesco Fiorillo, Roberto Grella, Roberto Lacava, Antonio Maddonni, Saverio Marino, Alice Pluderi, Daria Putignano, Filomena RoccaAssociazione Geriatri Extraospedalieri – Geriatria Italiana Territoriale, Tenore 17, Naples, ItalyAbstract: A significant percentage of elderly subjects (50%–80%) suffering from sub-acute ischemic cerebrovascular disease, with or without moderate or severe cognitive memory decline and with or without associated behavioral and psychological symptoms, shows a complex syndrome. This syndrome is related to the progressive impairment of health conditions and/or stressing events (ie, hospitalization), characterized by confusion and/or stupor, which are consequently difficult to manage and require a great deal of care. Geriatric patients often suffer from multiple chronic illnesses, may take numerous medications daily, exhibit clinical instability, and may experience worsening of medical conditions following cerebral ischemic events and thus have an increased risk of disability and mortality. There are several studies in literature which demonstrate the efficacy of citicoline, thanks to its neuroprotective function, for the recovery and in postischemic cerebral rehabilitation. It has been shown that, even soon after an ischemic stroke, administration of oral citicoline (500–4000 mg/day) improves the general conditions evaluated with the Rankin scale and the National Institute of Health Stroke Scale 12. In particular, it has been shown that the CDP-choline improves the cognitive and mental performance in Alzheimer's dementia and vascular dementia. We have evaluated the administration of citicoline in geriatric patients following a protocol of intravenous study on improvement of individual performances.Keywords: geriatric syndrome, citicoline, Alzheimer's disease, cerebrovascular disease, comorbiditiesCorrigendum for this paper has been published

Putignano S, Gareri P, Castagna A, Cerqua G, Cervera P, Cotroneo AM, Fiorillo F, Grella R, Lacava R, Maddonni A, Marino S, Pluderi A, Putignano D, Rocca F. Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome. Clin Interv Aging. 2012;7:113–118.One of the author’s names was listed incorrectly as Roberto Grella, it should have been Rodolfo Grella.Read the original article