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

Background To operationalize the National Institute on Aging - Alzheimer's Association (NIA-AA) Research Framework for Alzheimer's Disease 6-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 3 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 (Delta OBJ), and new onset of neurobehavioral symptoms (Delta NBS). We calculated frequencies of the stages using different cutoff points and assessed stability of the stages over 15 months. Results Among 243 abnormal amyloid participants, the frequencies of the stages varied with age: 66 to 90% were classified as stage 1 at age 50 but at age 80, 24 to 36% were stage 1, 32 to 47% were stage 2, 18 to 27% were stage 3, 1 to 3% were stage 4 to 6, and 3 to 9% were indeterminate. Most stage 2 participants were classified as stage 2 because of abnormal Delta OBJ only (44-59%), whereas 11 to 21% had SCD only, and 9 to 13% had Delta NBS only. Short-term stability varied by stage and OBJ cutoff points but the most notable changes were seen in stage 2 with 38 to 63% remaining stable, 4 to 13% worsening, and 24 to 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. ANN NEUROL 2021

Automated summary

This study evaluated 243 participants with abnormal amyloid and found that the frequencies of stages varied by age and the stability of each stage differed. Further revision and research are needed before the staging framework can be adopted for clinical trials.