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Background: Citicoline can have beneficial effects both in degenerative and in vascular cognitive decline in a variety of ways (apoptosis inhibition, neuroplasticity potentiation, phospholipid, and acetylcholine (ACh) synthesis). Acetylcholinesterase inhibitors (AChEIs) have been used for treatment of Alzheimer's disease (AD). When co-administered with cholinergic precursors, they are able to increase the intrasynaptic levels of ACh more than when the single drugs given alone., Objective: The aim of the present study was to show the effectiveness of oral citicoline plus AChEIs in patients affected with AD., Methods: This was a retrospective multi-centric case-control study, involving seven Centers for Cognitive Impairment and Dementia in Italy, on 448 consecutive patients aged 65 years old or older affected with AD. 197 patients were treated with an AChEI while 251 were treated with an AchEI + citicoline 1000 mg/day given orally. Cognitive functions were assessed by MMSE, daily life functions by ADL and IADL, behavioral symptoms by NPI, comorbidities by CIRS, and mood by GDS-short form. Tests were administered at baseline (T0), after 3 (T1), and 9 months (T2). The primary outcomes were effects of combined administration versus AChEIs given alone on cognitive functions assessed by MMSE. The secondary outcomes were possible side effects or adverse events of combination therapy versus AChEIs alone., Results: Patients treated with citicoline plus an AChEI showed a statistically significant increase in MMSE between T0 and T1 (16.88±3.38 versus 17.62±3.64; p = 0.000) and between T1 and T2 (17.62±3.64 versus 17.89±3.54; p = 0.000)., Conclusion: The present study encourages the role of combined administration in disease management by slowing disease progression.

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., 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.

Background: Combined therapy of memantine and acetylcholinesterase inhibitors (AChEIs) in patients with Alzheimer's disease (AD) may be associated with higher benefits than either monotherapy., Objective: This retrospective multicentric study conducted in seven Italian Ambulatory Centers for Dementia assessed the efficacy and safety of memantine 20 mg/day administered for 6 months in addition to an AChEI in AD patients with worsened cognitive functions and behavioral disorders., Methods: A total number of 240 patients (61.7% of women, 38.3% men, mean age 77.9 ± 7.32 years old) who had started treatment with the combination therapy were recruited. At baseline (T0), Month 3 (T1), and Month 6 (T2), cognitive functions were assessed by Mini-Mental State Examination (MMSE), functional dependence by activities of daily living (ADL) and instrumental ADL, behavioral disturbances by the Neuropsychiatric Inventory (NPI), and comorbidities by Cumulative Illness Rating Scale. Adverse events were reported during the study., Results: MMSE total score significantly increased at Month 6 (p = 0.029 versus month 3) and IADL total score significantly decreased from baseline to endpoint (p = 0.033). There were no significant changes from baseline in mean ADL, despite significant improvements in NPI total score. The mean MMSE total score significantly increased with the combination donepezil + memantine compared to rivastigmine + memantine. The adverse events profile was in line with the expected range of the drugs studied and concomitant therapies. Overall, 17 patients discontinued treatment in the observation time., Conclusion: Combined treatment with memantine and AChEIs was effective in patients with AD, particularly in slowing cognitive impairment and preventing the onset of agitation and aggression in elderly AD patients.

Background: 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.

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.