Neurology Learning NetworkDeferiprone Accelerates Cognitive Decline in Patients with Early AD

A recent phase 2 randomized controlled trial reveals that deferiprone (15 mg/kg twice daily) may accelerate cognitive decline in patients with early Alzheimer’s disease (AD). The 12-month study, conducted across 9 Australian sites, demonstrated significant cognitive deterioration in the deferiprone group compared to placebo, challenging previous assumptions about iron’s role in AD progression.

Key Points:

• Trial data showed accelerated cognitive decline in the deferiprone group (NTB composite z score change: -0.80; 95% CI, -0.98 to -0.62) versus placebo (-0.30; 95% CI, -0.54 to -0.06), with a significant interaction effect (β = -0.50; 95% CI, -0.80 to -0.20)
• The study included 81 participants (deferiprone n=53, placebo n=28) with amyloid-confirmed mild cognitive impairment or early AD, requiring a Mini-Mental State Examination score of 20 or higher
• Quantitative susceptibility mapping confirmed decreased hippocampal iron with deferiprone treatment (-0.36 ppb) compared to placebo (0.32 ppb), while exploratory analysis revealed increased frontal area volume loss
• Safety concerns emerged with a 7.5% neutropenia rate in the deferiprone group, higher than previous studies, alongside a substantial dropout rate (37.7% deferiprone, 25% placebo)
• Study limitations included COVID-19 recruitment impacts, potential unmasking due to neutropenia rates, and absence of long-term follow-up beyond 12 months

HCN Medical Memo
This trial’s findings necessitate careful reconsideration of iron-targeting therapeutic approaches in AD treatment, suggesting that iron elevation may serve a protective rather than pathological role in disease progression.

Drug Safety & Interactions Summaries