Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment

Abstract

Background: Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment after stroke. We assessed the safety of long-term administration and its possible efficacy of citicoline in preventing poststroke cognitive decline in patients with first-ever ischemic stroke. Methods: Open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a qualifying stroke and randomized by age, gender, education and stroke type into parallel arms of citicoline (1 g/day) for 12 months vs. no citicoline (control group). Medical management was similar otherwise. All patients underwent neuropsychological evaluation at 1 month, 6 months and 1 year after stroke. Tests results were combined to give indexes of 6 neurocognitive domains: attention and executive function, memory, language, spatial perception, motor speed and temporal orientation. Using adjusted logistic regression models we determined the association between citicoline treatment and cognitive decline for each neurocognitive domain at 6 and 12 months. Results: We recruited 347 subjects (mean age 67.2 years, 186 male (56.6%), mean education 5.7 years); 172 (49.6%) received citicoline for 12 months (no significant differences from controls n = 175). Demographic data, risk factors, initial stroke severity (NIHSS), clinical and etiological classification were similar in both groups. Only 37 subjects (10.7%) discontinued treatment (10.5% citicoline vs. 10.9% control) at 6 months; 30 (8.6%) due to death (16 (9.3%) citicoline vs. 14 (8.0%) control, p = 0.740), 7 lost to follow-up or incorrect treatment, and 4 (2.3%) had adverse events from citicoline without discontinuation. 199 patients underwent neuropsychological evaluation at 1 year. Cognitive functions improved 6 and 12 months after stroke in the entire group but in comparison with controls, citicoline-treated patients showed better outcome in attention-executive functions (OR 1.721, 95% CI 1.065–2.781, p = 0.027 at 6 months; OR 2.379, 95% CI 1.269–4.462, p = 0.007 at 12 months) and temporal orientation (OR 1.780, 95% CI 1.020–3.104, p = 0.042 at 6 months; OR 2.155, 95% CI 1.017–4.566, p = 0.045 at 12 months) during the follow-up. Moreover, citicoline group showed a better functional outcome (modified Rankin scale ≤2) at 12 months (57.3 vs. 48.7%) without statistically significant differences (p = 0.186). Conclusions: Citicoline treatment for 12 months in patients with first-ever ischemic stroke is safe and probably effective in improving poststroke cognitive decline. Citicoline appears to be a promising agent to improve recovery after stroke. Large clinical trials are needed to confirm the net benefit of this therapeutic approach.

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

“…There were difficulties due to heterogeneity of the articles, but even with these technical difficulties there was evidence of certain benefit for memory, behavior and global clinical impression in the medium and short term, especially in patients with cognitive deficits associated with cerebrovascular disorders [228]. Subsequently, a randomized, open-label study comparing citicoline to placebo for 12 months was published to assess the effectiveness of citicoline in preventing post-stroke cognitive impairment in patients who had a first ischemic stroke event; benefits in executive function and guidance were found [229,230]. Simultaneously, the IDEALE study was published, comparing oral citicoline (1000 mg/day) to placebo for mild VCI for 9 months.…”

Speech Disorders and Their Correction in Post-Stroke Patients

“…Данные последнего метаанализа также подтверждают положительный эффект препарата у пациентов с ишеми-ческим инсультом [7]. Помимо этого показана эффектив-ность цитиколина при постинсультных когнитивных и двигательных расстройствах [15,16]. Положительное влияние препарата на речевые нарушения у пациентов после инсульта отдельно не оценивалось, однако можно предположить, что стимуляция механизмов нейрональ-ной пластичности и активация большинства нейротранс-миттерных систем могут способствовать улучшению речевых функций.…”

Poststroke cognitive impairment and dementia

“…Наконец, цитиколин способствует снижению выраженности когнитивных нару-шений после ишемического инсульта, что было показано в открытом исследовании с участием 347 пациентов, 6 нед. назад перенесших инсульт [2]. Через 1 год лечения цити-колином в дозе 1 г/сут внутрь у значимо большей доли пациентов отмечалось улучшение таких аспектов, как под-держание внимания и ориентация во времени.…”