P1‐016: methylphenidate improves executive functioning in patients with vascular cognitive impairment: first results of the stream‐vci study

Patients with vascular cognitive impairment (VCI) constitute a clinically heterogeneous group. Some patients suffer from executive dysfunctioning, whereas others experience memory impairment. Currently, there is no symptomatic treatment for patients with VCI. In STREAM-VCI, we investigated whether a monoaminergic challenge (methylphenidate) improves executive functioning and whether a cholinergic challenge (galantamine) improves memory in VCI. STREAM-VCI is a single center, double blind, three-way case cross-over trial. We included 30 VCI patients (MMSE ≥16 and CDR 0.5-1.0). All patients received a single dose of methylphenidate (10mg), galantamine (16mg), or placebo in random order on three separate occasions. We used a computerized neuropsychological test battery to assess cognition. Our main outcome was defined as the change in performance measured directly after a pharmacological challenge on the adaptive tracker for executive functioning and on the Visual Verbal Learning Test-15 (VVLT-15) for memory. The adaptive tracker was assessed three times after each challenge. The VVLT-15 contains immediate, delayed and recognition word recall, assessed once after each challenge. We performed mixed model analyses of variance. For the adaptive tracker, we used treatment, period, time, and treatment by time as fixed factors and participant, participant by treatment and participant by time as random factors and the average baseline measurement as covariate on each time point. For the VVLT-15, we used treatment and period as fixed factors and subjects as random factor. The study population had a mean age of 67±8years, an MMSE of 26±3 and 30% was female. Methylphenidate improved performance on the adaptive tracker more than placebo (mean difference 1.40; 95%CI 0.56–2.25) and galantamine (mean difference 1.38; 95%CI 0.53–2.23) (Figure 1). In addition, methylphenidate led to better performance on the third trial of the immediate recall of the VVLT-15 compared to placebo (mean difference in recalled words 0.59; 95%CI 0.03–1.15; p=0.04) and galantamine (mean difference 1.11; 95%CI 0.56–1.67; p<0.001). Galantamine did not improve performance on adaptive tracker or VVLT-15. Effect of the pharmacological challenges on adaptive tracker as measure of executive functioning. Figure represents the estimates of difference in performance on the adaptive tracker (the average velocity as percentage of the maximum velocity possible) 1 hour, 2,5 and 3,5 hours after administration of the drug (time point 0). The shaded area represents the 95% confidence interval. *p-value for the difference between methylfenidate and placebo, **p value for the difference between methylphenidate and galantamine. In this proof of concept trial in patients with VCI, methylphenidate improved tests of executive functioning and immediate recall, whereas galantamine did not.