From the Research
The primary endpoints studied in new Alzheimer's infusion therapies like aducanumab focused on amyloid plaque reduction and cognitive function changes, with the most recent and highest quality study indicating a 30% slowing of cognitive and functional decline over 18 months 1. The EMERGE trial reported a modest slowing of cognitive decline as measured by the Mini-Mental State Examination (MMSE), with treated patients showing approximately 0.5-0.7 points less decline compared to placebo over 18 months. On the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the high-dose treatment group demonstrated about 1.4 points less worsening. However, these cognitive benefits were inconsistent across trials, with the ENGAGE trial failing to replicate these findings. Other emerging therapies like lecanemab and donanemab have shown similar patterns - significant amyloid clearance with modest cognitive benefits of approximately 27-35% slowing of decline compared to placebo. These therapies work by targeting and removing amyloid beta plaques in the brain, which are hallmarks of Alzheimer's disease, but the relationship between plaque removal and meaningful cognitive improvement remains complex. Some key points to consider include:
- Aducanumab demonstrated a dose-dependent reduction in amyloid plaques but showed mixed results regarding cognitive benefits 2, 3.
- The most common adverse event was amyloid-related imaging abnormalities (ARIA), which occurred at rates up to 47% in the 10 mg/kg group 2.
- ARIA can cause brain swelling or microhemorrhages, requiring careful monitoring through MRI scans during treatment 4.
- The incidence of ARIA was highest in aducanumab-treated participants who were apolipoprotein E ε4 allele carriers 4.
- Most events among those with ARIA resolved radiographically, with 82.8% resolving within 16 weeks 4. In clinical practice, the use of aducanumab should be carefully considered, weighing the potential benefits of slowing cognitive decline against the risks of ARIA and other adverse events, and monitoring patients closely for any signs of these complications 1, 5.