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

Alzheimers Dement. 2022 Dec;18(12):2403-2412. doi: 10.1002/alz.12516. Epub 2022 Feb 9.

Abstract

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.

Keywords: Alzheimer disease; Lewy bodies; amyloid angiopathy; cognitive decline; dementia; hippocampal sclerosis; neuritic plaques; neurofibrillary; neuropathology; tangles; vascular dementia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / pathology
  • Brain / pathology
  • Cognitive Dysfunction* / pathology
  • Humans
  • Lewy Bodies / pathology
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / pathology

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