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

Authors

• Susan M. Landau, University of California Berkeley, Berkeley, California, USA.
• Peiwei Liu, University of California Berkeley, Berkeley, California, USA.
• Theresa M. Harrison, University of California Berkeley, Berkeley, California, USA.
• Jacinda Taggett, University of California Berkeley, Berkeley, California, USA.
• Tyler J. Ward, University of California Berkeley, Berkeley, California, USA.
• Alice Murphy, University of California Berkeley, Berkeley, California, USA.
• Samuel N. Lockhart, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.Follow
• Laura C. Lovato, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.Follow
• Robert Koeppe, University of Michigan, Ann Arbor, Michigan, USA.
• Sarah Tomaszewski Farias, University of California Davis, Davis, California, USA.
• Kathryn V. Papp, Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA.
• Heather M. Snyder, Alzheimer's Association, Chicago, Illinois, USA.
• Danielle J. Harvey, University of California Davis, Davis, California, USA.
• Mark Espeland, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.Follow
• Pauline Maillard, University of California Davis, Davis, California, USA.
• Charles DeCarli, University of California Davis, Davis, California, USA.
• Prashanthi Vemuri, Mayo Clinic, Rochester, Minnesota, USA.
• Michael Weiner, Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, San Francisco, California, USA.
• Laura D. Baker, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
• William J. Jagust, University of California Berkeley, Berkeley, California, USA.
• U.S. POINTER Study Group and Alzheimer's Disease Neuroimaging Initiative
• Darren Gitelman, Advocate Health - MidwestFollow

Recommended Citation

Landau SM, Liu P, Harrison TM, et al. Elevated AD biomarkers do not explain cognitive performance in a community-recruited clinical trial cohort. Alzheimers Dement. 2026;22(5):e71472. doi:10.1002/alz.71472

Abstract

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.

Type

Article

PubMed ID

42151735