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Four Distinct Alzheimer’s Progression Pathways Validated in Diverse Cohorts

Outperforming single-condition models, multi-step diagnostic trajectories pave the way for targeted early interventions

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Overview

  • Researchers analyzed longitudinal electronic health records from nearly 25,000 University of California Health Data Warehouse patients to uncover sequential diagnostic patterns leading to Alzheimer’s disease.
  • The study identified four progression trajectories—mental health, encephalopathy, mild cognitive impairment and vascular disease—that map step-by-step routes toward dementia.
  • Validation in the nationally diverse All of Us Research Program confirmed that these multi-step pathways predict Alzheimer’s risk more accurately than single diagnoses alone.
  • About 26 percent of diagnostic sequences exhibited consistent directional ordering, with examples such as hypertension preceding depressive episodes that increase dementia risk.
  • Each trajectory displayed distinct demographic and clinical profiles, suggesting new opportunities for refined risk stratification and personalized prevention strategies.