ArticleNeurology2026
Eligibility for Anti-Amyloid Therapies in Patients With Biomarker-Confirmed Atypical Alzheimer Disease Phenotypes.
Article in Neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectivesClinical trials of anti-amyloid therapies (AATs) for Alzheimer disease (AD) primarily enrolled patients with mildly symptomatic, amnestic predominant presentations. The applicability of eligibility criteria to atypical AD phenotypes, including posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), dysexecutive AD (dAD), and corticobasal syndrome because of AD (CBS-AD), is unknown.
methodsWe conducted a retrospective eligibility analysis of patients with atypical AD evaluated at Mayo Clinic. Theoretical eligibility for AAT was assessed at initial clinical evaluation by applying inclusion and exclusion criteria from landmark clinical trials (Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease [CLARITY-AD] and the Study of LY3002813 (Donanemab) in Participants With Early Symptomatic Alzheimer's Disease [TRAILBLAZER-ALZ2]) and appropriate use criteria for lecanemab and donanemab. Eligibility percentages and reasons for exclusion were compared across phenotypes.
resultsThe cohort included 184 patients (61.4% female) with biomarker-confirmed atypical AD: PCA (n = 98, 53.3%), lvPPA (n = 42, 22.8%), dAD (n = 37, 20.1%), and CBS-AD (n = 7, 3.8%). Age at onset ( DISCUSSION: Most patients with atypical AD would not meet eligibility criteria for AAT, typically because of MMSE-based exclusion rather than measures of cognitive function. Eligibility rates are broadly similar across atypical phenotypes. These findings highlight the need for phenotype-sensitive staging and patient selection for treatment in atypical AD.
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