Abstract Details

Title Donanemab in Early Alzheimer’s Disease: Greater Benefit in Lower Tau Burden

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-011

Objective

To evaluate the effect of donanemab compared to placebo on cognitive and functional outcomes in Alzheimer’s disease (AD) patients stratified by tau burden (low/medium [L/M] vs. high [H]).

Background Donanemab, an anti-amyloid monoclonal antibody, has shown promise in slowing cognitive decline in early AD. Tau-pathology may influence treatment response, but subgroup effects remain unclear.

Design/Methods We systematically reviewed placebo-controlled trials of donanemab in AD reporting outcomes by tau burden. Standardized mean differences (SMD) with 95% confidence intervals (CI) were pooled using inverse-variance methods under fixed- and random-effects models. Outcomes included the integrated Alzheimer’s Disease Rating Scale (iADRS), Clinical Dementia Rating–Sum of Boxes (CDR-SB), ADAS-Cog13, ADCS-iADL, and MMSE.

Results

Donanemab significantly improved iADRS (g = 3.07; 95% CI 1.49–4.65; p = 0.0001) and favored treatment on CDR-SB (g = –0.61; 95% CI –0.82 to –0.40), ADAS-Cog13 (g = –1.54; 95% CI –2.21 to –0.86), ADCS-iADL (g = 1.70; 95% CI 0.93–2.47), and MMSE (g = 0.53; 95% CI 0.18–0.89). Subgroup analysis showed greater benefit in L/M tau versus H tau across most outcomes: iADRS (L/M: g = 3.80; 95% CI 2.37–5.23; H: g = 0.94; 95% CI –2.16 to 4.04), CDR-SB (L/M: g = –0.67; 95% CI –0.94 to –0.40; H: g = –0.69; 95% CI –1.18 to –0.20), ADAS-Cog13 (L/M: g = –1.72; 95% CI –2.52 to –0.92; H: g = –0.40; 95% CI –2.11 to 1.31), ADCS-iADL (L/M: g = 2.00; 95% CI 1.06–2.94; H: g = 0.99; 95% CI –0.81 to 2.79), and MMSE (L/M: g = 0.57; 95% CI 0.14–1.00; H: g = 0.33; 95% CI –0.47 to 1.13). Between-group differences were not statistically significant (p > 0.25). Heterogeneity was low (I² ≤ 26%).

Conclusions Donanemab demonstrates clinically meaningful benefits in early AD, particularly among patients with lower tau-burden. While high-tau patients showed attenuated responses, subgroup differences were not statistically significant.

Authors/Disclosures
Aswathi Sajeendran, MD PRESENTER	Dr. Sajeendran has nothing to disclose.
Jamir Pitton Rissardo, MD	Dr. Pitton Rissardo has nothing to disclose.
Omar Elmandouh, MD	Dr. Elmandouh has nothing to disclose.
Ana Leticia Fornari Caprara, MD	Dr. Fornari Caprara has nothing to disclose.

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