Alzheimer's & Dementia · May 2026

Elevated AD biomarkers do not explain cognitive performance in a community-recruited clinical trial cohort

By Landau SM, Liu P, Harrison TM et al.

INTRODUCTION: To examine the generalizability of Alzheimer's disease (AD) biomarker models in real-world older adults, we examined AD biomarker relationships with cognition in two multicenter cohorts that differ with respect to recruitment approach and health risk factors but were matched on a variety of characteristics. METHODS: We compared harmonized health and demographic data, AD and cerebrovascular biomarkers, and cognitive performance in the community-recruited U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) Imaging substudy and a matched sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) which recruited primarily from academic specialty clinics. RESULTS: Elevated β-amyloid (Aβ) and tau were associated with cognitive performance in ADNI but not U.S. POINTER. Findings were consistent across different cohort matching schemes, and were not explained by discrepancies in vascular risk. DISCUSSION: The role of Aβ and tau in cognitive performance may be reduced in real world samples compared to academic specialty clinics.

doi.org/10.1002/alz.71472 Open access PubMed 42151735 Biomarkers