title: 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.
authors: Department of Neurology, Neurovascular Unit, Universitat Autónoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain. josalvarez@vhebron.net
authors: Jose
authors: J
authors: Alvarez-Sabín
authors: Gemma
authors: G
authors: Ortega
authors: Carlos
authors: C
authors: Jacas
authors: Estevo
authors: E
authors: Santamarina
authors: Olga
authors: O
authors: Maisterra
authors: Marc
authors: M
authors: Ribo
authors: Carlos
authors: C
authors: Molina
authors: Manuel
authors: M
authors: Quintana
authors: Gustavo C
authors: GC
authors: Román
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage* / Q000009:adverse effects; D015140:Dementia, Vascular / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D011237:Predictive Value of Tests; D020127:Recovery of Function; D013030:Spain; D020521:Stroke / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D000071939:Stroke Rehabilitation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline