Dana Godrich1, Eden R Martin1,2, Gerard Schellenberg3, Margaret A Pericak-Vance1,2, Michael Cuccaro1,2, William K Scott1,2, Walter Kukull4, Thomas Montine5, Gary W Beecham1,2. 1. Dr. John T MacDonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, Florida, USA. 2. John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, USA. 3. Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 4. Department of Epidemiology, University of Washington, Seattle, Washington, USA. 5. Department of Pathology, Stanford University, Stanford, California, USA.
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.
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.
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