Neuropathological lesions and their contribution to dementia and cognitive impairment in a heterogeneous clinical population

Dana Godrich, Eden R. Martin, Gerard Schellenberg, Margaret A. Pericak-Vance, Michael Cuccaro, William K. Scott, Walter Kukull, Thomas Montine, Gary W. Beecham

Research output: Contribution to journalArticlepeer-review


Introduction: Alzheimer disease (AD) and related dementias are characterized by damage caused by neuropathological lesions in the brain. These include AD lesions (plaques and tangles) and non-AD lesions such as vascular injury or Lewy bodies. We report here an assessment of lesion association to dementia in a large clinic-based population. Methods: We identified 5272 individuals with neuropathological data from the National Alzheimer's Coordinating Center. Individual lesions, as well as a neuropathological composite score (NPCS) were tested for association with dementia, and both functional and neurocognitive impairment using regression models. Results: Most individuals exhibited mixed pathologies, especially AD lesions in combination with non-AD lesions. All lesion types were associated with one or more clinical outcomes; most even while controlling for AD pathology. The NPCS was also associated with clinical outcomes. Discussion: These data suggest mixed-type pathologies are extremely common in a clinic-based population and may contribute to dementia and cognitive impairment.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
StateAccepted/In press - 2022


  • Alzheimer disease
  • Lewy bodies
  • amyloid angiopathy
  • cognitive decline
  • dementia
  • hippocampal sclerosis
  • neuritic plaques
  • neurofibrillary
  • neuropathology
  • tangles
  • vascular dementia

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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