Hiroko H Dodge1, Jian Zhu2, Randy Woltjer3, Peter T Nelson4, David A Bennett5, Nigel J Cairns6, David W Fardo7, Jeffrey A Kaye8, Deniz-Erten Lyons8, Nora Mattek3, Julie A Schneider9, Lisa C Silbert8, Chengjie Xiong10, Lei Yu5, Frederick A Schmitt11, Richard J Kryscio7, Erin L Abner12. 1. Layton Aging and Alzheimer's Disease Center, Department of Neurology, Oregon Health & Science University, Portland, OR; Michigan Alzheimer's Disease Center, Department of Neurology, University of Michigan, Ann Arbor, MI. Electronic address: dodgeh@ohsu.edu. 2. School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI. 3. Layton Aging and Alzheimer's Disease Center, Department of Neurology, Oregon Health & Science University, Portland, OR. 4. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY; Department of Pathology, University of Kentucky, Lexington, KY. 5. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL. 6. Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO. 7. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY; College of Public Health, Department of Biostatistics, University of Kentucky, Lexington, KY. 8. Layton Aging and Alzheimer's Disease Center, Department of Neurology, Oregon Health & Science University, Portland, OR; Portland VA Medical Center, Portland, OR. 9. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL; Department of Pathology, Rush University Medical Center, Chicago, IL. 10. Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO. 11. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY; College of Medicine, Departments of Neurology and Psychiatry, University of Kentucky, Lexington, KY. 12. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY; College of Public Health, Department of Epidemiology, University of Kentucky, Lexington, KY.
Abstract
INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD). METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). RESULTS: The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. DISCUSSION: Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required.
INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD). METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). RESULTS: The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. DISCUSSION: Our results reinforce the diagnostic importance of AD pathology in clinicalAD. Further harmonization of assessment approaches for vascular pathologies is required.
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