2026 American Academy of Neurology Abstract Website

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.