Deferiprone Fails to Improve Cognition in Early Alzheimer's Trial, Raises Concerns
Key Insights
A clinical trial investigating deferiprone, an iron chelator, in patients with mild cognitive impairment or early Alzheimer's, showed reduced iron levels in the hippocampus but accelerated cognitive decline.
The 12-month study randomized 81 participants to either deferiprone (15 mg/kg twice daily) or placebo and assessed cognitive function, including memory and executive function.
While deferiprone effectively lowered iron levels in the hippocampus, patients receiving the drug experienced a worsening of executive function compared to the placebo group.
A recent clinical trial investigating the use of the iron chelator deferiprone in patients with early Alzheimer's disease (search) has raised concerns after it showed accelerated cognitive decline despite reducing iron levels in the brain. The study, a collaboration between multiple Australian institutions, including the Florey Institute of Neuroscience and Mental Health (search), challenges the hypothesis that reducing brain iron can improve cognitive function in Alzheimer's patients.
The trial, published in JAMA Neurology, involved 81 participants over the age of 54 with mild cognitive impairment or early Alzheimer's disease (search), all of whom had confirmed amyloid (search) deposits. Participants were randomized to receive either 15 mg/kg of oral deferiprone twice daily or a placebo for 12 months. The primary outcome was improved cognitive functioning, specifically memory, executive function, and attention, assessed at baseline, six, and 12 months. Secondary outcomes included changes in brain iron levels.
Iron Reduction and Cognitive Decline
MRI results indicated that deferiprone effectively reduced iron levels in the hippocampus, a brain region critical for memory, compared to the placebo group. However, contrary to expectations, patients treated with deferiprone exhibited accelerated cognitive decline, primarily driven by worsening performance on executive function tests. Executive functions encompass higher-level mental processes essential for planning, focus, memory, and multitasking.
Implications and Context
These findings contradict previous assumptions about the therapeutic potential of iron chelation in Alzheimer's disease (search). While iron accumulation in the brain has been implicated in the pathogenesis of Alzheimer's, this study suggests that simply lowering iron levels may not be beneficial and could even be harmful. The researchers caution against the use of deferiprone as a treatment for Alzheimer's disease based on these results.
Deferiprone is currently used to treat iron overload in individuals with blood disorders like thalassemia and sickle cell anemia who require frequent blood transfusions. The trial's results highlight the complexity of Alzheimer's disease (search) and the need for careful consideration of potential therapeutic targets and interventions. Further research is needed to fully understand the role of iron in Alzheimer's pathology and to identify effective strategies for preventing and treating this devastating condition.