Fluoxetine May Enhance VEGF, BDNF and Cognition in Patients with Vascular Cognitive Impairment No Dementia: An Open-Label Randomized Clinical Study

PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) enhance angiogenesis and neurogenesis. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) play an important role in neurogenesis and angiogenesis. However, the effect of SSRIs on cognition and serum BDNF and VEGF in patients with vascular cognitive impairment no dementia (VCIND) is largely unknown. PATIENTS AND METHODS: It was an open label study. Fifty VCIND patients were randomly allocated to receive fluoxetine (20 mg/d; n = 25) or no fluoxetine (control group; n = 25) for 12 weeks. VCIND patients received fluoxetine 20 mg/d and secondary prevention of stroke for 12 weeks in the fluoxetine group, whereas the control group received only secondary prevention of stroke for 12 weeks. The primary outcome and secondary outcome were of assessment of Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog) score, Ten Point Clock drawing test score (TPC), Verbal Fluency Test (VFT), Trail Making Test form a (TMTa), Trail Making Test form b (TMTb) and Digit Span Test score at baseline and week 12 in the both groups. And serum concentration of BDNF and VEGF was also tested at baseline and week 12 in both groups. RESULTS: After 12 weeks, TPC scores increased more significantly in the fluoxetine group than in the control group, while TMTa score and TMTb score were decreased more significantly in the fluoxetine group than in the control group. We also found that the serum concentration of BDNF and VEGF in the fluoxetine group increased more significantly than in the control group. However, we found no significant differences in mean change from baseline between fluoxetine and control group in ADAS-Cog score, Digit Span Test score and VFT score. CONCLUSION: Fluoxetine may enhance cognition in certain cognitive domains and serum concentration of BDNF and VEGF in patients with VCIND.