NIA-AA Alzheimer's Disease Framework: Clinical Characterization of Stages

Ronald C Petersen, Heather J Wiste, Stephen D Weigand, Julie A Fields, Yonas E Geda, Jonathan Graff-Radford, David S Knopman, Walter K Kremers, Val Lowe, Mary Machulda, Michelle Mielke, Nikki H Stricker, Terry M Therneau, Prashanthi Vemuri, Clifford R Jack
Annals of Neurology 2021 March 26

BACKGROUND: To operationalize the National Institute on Aging-Alzheimer's Association Research Framework for Alzheimer's Disease six-stage continuum of clinical progression for persons with abnormal amyloid.

METHODS: The Mayo Clinic Study of Aging is a population-based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. We evaluated persons without dementia having three consecutive clinical visits. Measures for cross-sectional categories included objective cognitive impairment (OBJ) and function (FXN). Measures for change included subjective cognitive impairment (SCD), objective cognitive change (ΔOBJ), and new onset of neurobehavioral symptoms (ΔNBS). We calculated frequencies of the stages and assessed stability of the stages over 15 months.

RESULTS: Among 243 abnormal amyloid participants, the frequencies of the stages varied with age: 66-90% were classified as Stage 1 at age 50 but at age 80, 24-36% were Stage 1, 32-47% Stage 2, 18-27% Stage 3, 1-3% Stage 4-6, and 3-9% indeterminate. Most Stage 2 participants were classified as Stage 2 because of abnormal ΔOBJ only (44-59%), while 11-21% had SCD only, and 9-13% had ΔNBS only. Short-term stability varied by stage and OBJ cut points but the most notable changes were seen in Stage 2 with 38-63% remaining stable, 4-13% worsening, and 24-41% improving (moving to Stage 1).

INTERPRETATION: The frequency of the stages varied by age and the precise membership fluctuated by the parameters used to define the stages. The staging framework may require revisions before it can be adopted for clinical trials. This article is protected by copyright. All rights reserved.

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