To review the performance, limitations, and cross-cultural adaptations of cognitive screening tools used to determine eligibility for anti-amyloid therapies, emphasizing their diagnostic equity in multicultural settings.

Anti-amyloid monoclonal antibodies such as lecanemab and donanemab have transformed Alzheimer’s disease care by offering some of the first disease-modifying treatment options. Eligibility for these therapies relies on accurate cognitive staging, typically determined by brief screening tools such as the Mini-Mental State Examination and Montreal Cognitive Assessment. However, test validity varies across languages, cultures, and education levels in diverse populations, which raises concerns about equitable diagnosis and access. These limitations reinforce the need for careful clinical judgment when interpreting scores.

A comprehensive literature search identified studies examining the MMSE, MoCA, and related adaptations, focusing on translation validity, cultural equivalence, and psychometric performance in immigrant and low-literacy populations. Trials informing the use of these tools in the Clarity AD and TRAILBLAZER-ALZ2 studies and subsequent Appropriate Use Recommendations (AURs) were also reviewed.

Findings highlight that the MMSE and MoCA remain central to eligibility assessments but demonstrate reduced validity when language, education, or cultural context differs from that of test development. Cross-cultural adaptations such as the Arabic MMSE-2, Malian Mini-Mental State Examination (MAMSE), and region-specific MoCA versions improve accessibility and diagnostic accuracy by substituting unfamiliar stimuli, adjusting scoring for literacy, and integrating culturally relevant content. Combined administration of the MMSE-2 and Mini-Cog enhances sensitivity and specificity in low-literacy populations. Despite these advances, unvalidated adaptations risk introducing new biases if not psychometrically standardized.

Although cognitive screening tools guide eligibility for anti-amyloid therapies, they should not replace clinical evaluation. The literature supports clinician judgment as the most reliable determinant of diagnosis, particularly when cultural and educational factors influence test performance. As disease-modifying treatments expand, equitable implementation will depend on combining validated screening tools with informed, context-sensitive clinical assessment.