Does cohort heterogeneity affect relationships between AD biomarkers and cognition?

Cognitive performance was linked to all biomarkers (Aβ, tau, cortical thickness) but these associations were consistently stronger in ADNI compared to POINTER, particularly in Aβ+ individuals. The stronger thickness-cognition relationships in ADNI were not driven by tau, indicating that there is a tau-independent role of thickness in explaining cognition. In ADNI, there were subtle differences between cognitive domains such that executive function was more closely linked than verbal memory to Aβ and cortical thickness, whereas verbal memory was linked to tau in both cohorts. Our study highlights that frequently-reported AD biomarker associations may be attenuated in heterogeneous, community-recruited cohorts.