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

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.