Real-World Study Links Anti-Amyloid Therapy to Lower All-Cause Mortality in Alzheimer Disease
KEY TAKEAWAYS
- Anti-amyloid monoclonal antibody treatment was associated with lower all-cause mortality than no treatment in a propensity score-matched real-world cohort.
- During unrestricted follow-up, mortality was 1.1% in treated patients versus 8.3% in matched untreated controls.
- Findings suggest anti-amyloid therapy was not associated with excess mortality in routine clinical practice, although additional real-world safety studies are needed.
Treatment with anti-amyloid monoclonal antibodies was associated with substantially lower all-cause mortality than no treatment in a large real-world cohort of individuals with Alzheimer disease (AD), according to findings presented at the 2026 Alzheimer's Association International Conference (AAIC). The results add real-world evidence to ongoing discussions regarding the safety profile of amyloid-targeting therapies in routine clinical practice.
Investigators conducted a retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network to compare outcomes among patients with AD treated with anti-amyloid therapy (ATT)—including lecanemab and donanemab—and matched untreated controls. After 1:1 matching, the analysis included 1,078 patients in each group with balanced demographic and clinical characteristics. The primary outcome was all-cause mortality, assessed using unrestricted follow-up and a separate 1-year analysis.
Data Highlights
- All-cause mortality during unrestricted follow-up was 1.1% among ATT-treated patients compared with 8.3% in matched untreated controls.
- ATT was associated with significantly higher event-free survival (hazard ratio, 0.17; 95% CI, 0.09-0.31).
- In the 1-year analysis, no deaths occurred among ATT-treated patients, preventing estimation of a time-restricted hazard ratio.
- Agent-specific analyses for lecanemab and donanemab could not be performed because mortality events did not meet the minimum reportable threshold (<10 events).
The investigators concluded that anti-amyloid therapy was not associated with excess mortality and was associated with markedly lower all-cause mortality compared with matched untreated patients. Because of the retrospective observational design, the findings demonstrate an association rather than causation. The authors noted that additional real-world studies are needed to further evaluate the broader safety profile of anti-amyloid therapies.
Source
Almeida S, Gomes AC, Palmeira ALR, et al. Real-World Anti-Amyloid Therapy Is Associated With Lower All-Cause Mortality. Presented at the Alzheimer's Association International Conference (AAIC) 2026. Abstract.