ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes

Anja Soldan, Corinne Pettigrew, Anne M. Fagan, Suzanne E. Schindler, Abhay Moghekar, Christopher Fowler, Qiao Xin Li, Steven J. Collins, Cynthia Carlsson, Sanjay Asthana, Colin L. Masters, Sterling Johnson, John C. Morris, Marilyn Albert, Alden L. Gross

Research output: Contribution to journalArticle

Abstract

ObjectiveTo examine the long-term cognitive trajectories of individuals with normal cognition at baseline and distinct amyloid/tau/neurodegeneration (ATN) profiles.MethodsPooling data across 4 cohort studies, 814 cognitively normal participants (mean baseline age = 59.6 years) were classified into 8 ATN groups using baseline CSF levels of β-amyloid 1-42 as a measure of amyloid (A), phosphorylated tau 181 as a measure of tau (T), and total tau as a measure of neurodegeneration (N). Cognitive performance was measured using a previously validated global factor score and with the Mini-Mental State Examination. We compared the cognitive trajectories across groups using growth curve models (mean follow-up time = 7 years).ResultsUsing different model formulations and cut points for determining biomarker abnormality, only the group with abnormal levels of amyloid, tau, and neurodegeneration (A+T+N+) showed consistently greater cognitive decline than the group with normal levels of all biomarkers (A-T-N-). Replicating prior findings using the 2011 National Institute on Aging-Alzheimer's Association/suspected non-Alzheimer disease pathophysiology schema, only individuals with abnormal levels of both amyloid and phosphorylated tau 181 or total tau (stage 2) showed greater cognitive decline than those with normal biomarker levels (stage 0).ConclusionThe results are consistent with the hypothesis that both elevated brain amyloid and neurofibrillary tangles are necessary to observe accelerated neurodegeneration, which in turn leads to cognitive decline.

Original languageEnglish (US)
Pages (from-to)E1567-E1579
JournalNeurology
Volume92
Issue number14
DOIs
StatePublished - Apr 2 2019

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Soldan, A., Pettigrew, C., Fagan, A. M., Schindler, S. E., Moghekar, A., Fowler, C., Li, Q. X., Collins, S. J., Carlsson, C., Asthana, S., Masters, C. L., Johnson, S., Morris, J. C., Albert, M., & Gross, A. L. (2019). ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes. Neurology, 92(14), E1567-E1579. https://doi.org/10.1212/WNL.0000000000007248