J Psychopharmacol
Can a COPD drug boost memory after stroke? Roflumilast shows early promise
Clinical takeaway: Roflumilast (100 µg daily) demonstrated modest but potentially clinically relevant improvements in memory among patients with chronic post-stroke cognitive impairment, with a favorable safety profile—supporting further study but not yet routine use.
Post-stroke cognitive impairment affects up to 70% of survivors, yet no approved pharmacologic treatments meaningfully improve memory or cognition.
In a double-blind randomized controlled trial (ROSTMEMA) of 100 adults aged 41 to 70 years with prior stroke and persistent memory deficits, roflumilast was associated with improved performance on memory tests compared with placebo.
At study completion (n=97), patients receiving roflumilast (n=48) showed greater gains in verbal learning test (VLT) delayed recall and Rivermead Behavioural Memory Test scores than placebo (n=49), with moderate effect sizes (Cohen’s d ~0.31–0.36). After adjusting for baseline prognostic factors, these effects reached statistical significance (d ~0.33–0.40).
Importantly, adverse events were similar between groups, suggesting no major tolerability signal despite PDE4 inhibition.
In a 3-month open-label extension involving 42 prior placebo participants, memory scores improved further, with medium-to-large effect sizes (partial η² 0.079–0.171), reinforcing the signal seen in the randomized phase.
The authors note that “roflumilast appeared to improve memory and was not associated with adverse effects,” highlighting its potential as a novel strategy targeting synaptic plasticity pathways in post-stroke recovery.
While the cognitive gains were modest and sensitive to statistical adjustment, the findings provide early clinical support for PDE4 inhibition as a therapeutic avenue in post-stroke cognitive impairment—an area of significant unmet need.
Source: Kerckhoffs J, et al. (2026, April 24). J Psychopharmacol. The effects of the PDE4 inhibitor roflumilast on cognitive performance after a cerebrovascular accident: a double-blind randomized placebo-controlled trial with an open label extension (ROSTMEMA)