TY - JOUR
T1 - Long-term treatment with citicoline may improve poststroke vascular cognitive impairment
AU - Alvarez-Sabín, Jose
AU - Ortega, Gemma
AU - Jacas, Carlos
AU - Santamarina, Estevo
AU - Maisterra, Olga
AU - Ribo, Marc
AU - Molina, Carlos
AU - Quintana, Manuel
AU - Román, Gustavo C.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - Attention
KW - Citicoline
KW - Cognition
KW - Executive function
KW - Poststroke dementia
KW - Stroke
KW - Vascular dementia
UR - http://www.scopus.com/inward/record.url?scp=84873605697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873605697&partnerID=8YFLogxK
U2 - 10.1159/000346602
DO - 10.1159/000346602
M3 - Article
C2 - 23406981
AN - SCOPUS:84873605697
SN - 1015-9770
VL - 35
SP - 146
EP - 154
JO - Cerebrovascular Diseases
JF - Cerebrovascular Diseases
IS - 2
ER -