Ling Zheng1, Harry V Vinters, Wendy J Mack, Chris Zarow, William G Ellis, Helena C Chui. 1. From the Department of Neurology (L.Z., C.Z., H.C.C.), and Department of Preventive Medicine (W.J.M.), Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Neurology, University of California Los Angeles, Los Angeles, CA (H.V.V.); and Department of Neurology, University of California Davis, Sacramento, CA (W.G.E.).
Abstract
BACKGROUND AND PURPOSE: Some studies have reported associations between intracranial atherosclerosis and Alzheimer disease pathology. We aimed to correlate severity of cerebral atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy with neurofibrillary tangles, neuritic plaques, and cerebral infarcts. METHODS: This autopsy study (n=163) was drawn from a longitudinal study of subcortical ischemic vascular disease, Alzheimer disease, and normal aging. Multivariable logistic regression models were used to test associations among the 3 forms of cerebrovascular disease and the presence of ischemic and neurodegenerative brain lesions. Apolipoprotein E genotype was included as a covariate in these multivariable models. RESULTS: Cerebral atherosclerosis was positively associated with microinfarcts (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.4) and cystic infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Arteriolosclerosis showed a positive correlation with lacunar infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Cerebral amyloid angiopathy was inversely associated with lacunar infarcts (OR, 0.6; 95% CI, 0.41-1.1), but positively associated with Braak and Braak stage (OR, 1.5; 95% CI, 1.1-2.1) and Consortium to Establish a Registry for Alzheimer Disease plaque score (OR, 1.5; 95% CI, 1.1-2.2). CONCLUSIONS: Microinfarcts, which have been correlated with severity of cognitive impairment, were most strongly associated with atherosclerosis. Possible pathogenetic mechanisms include artery-to-artery emboli, especially microemboli that may include atheroemboli or platelet-fibrin emboli. Arteriolosclerosis was positively, whereas cerebral amyloid angiopathy was negatively correlated with lacunar infarcts, which might prove helpful in clinical differentiation of arteriolosclerotic from cerebral amyloid angiopathy-related vascular brain injury.
BACKGROUND AND PURPOSE: Some studies have reported associations between intracranial atherosclerosis and Alzheimer disease pathology. We aimed to correlate severity of cerebral atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy with neurofibrillary tangles, neuritic plaques, and cerebral infarcts. METHODS: This autopsy study (n=163) was drawn from a longitudinal study of subcortical ischemic vascular disease, Alzheimer disease, and normal aging. Multivariable logistic regression models were used to test associations among the 3 forms of cerebrovascular disease and the presence of ischemic and neurodegenerative brain lesions. Apolipoprotein E genotype was included as a covariate in these multivariable models. RESULTS:Cerebral atherosclerosis was positively associated with microinfarcts (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.4) and cystic infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Arteriolosclerosis showed a positive correlation with lacunar infarcts (OR, 2.0; 95% CI, 1.0-4.2) but not Alzheimer disease pathology. Cerebral amyloid angiopathy was inversely associated with lacunar infarcts (OR, 0.6; 95% CI, 0.41-1.1), but positively associated with Braak and Braak stage (OR, 1.5; 95% CI, 1.1-2.1) and Consortium to Establish a Registry for Alzheimer Disease plaque score (OR, 1.5; 95% CI, 1.1-2.2). CONCLUSIONS: Microinfarcts, which have been correlated with severity of cognitive impairment, were most strongly associated with atherosclerosis. Possible pathogenetic mechanisms include artery-to-artery emboli, especially microemboli that may include atheroemboli or platelet-fibrin emboli. Arteriolosclerosis was positively, whereas cerebral amyloid angiopathy was negatively correlated with lacunar infarcts, which might prove helpful in clinical differentiation of arteriolosclerotic from cerebral amyloid angiopathy-related vascular brain injury.
Authors: Helena C Chui; Chris Zarow; Wendy J Mack; William G Ellis; Ling Zheng; William J Jagust; Dan Mungas; Bruce R Reed; Joel H Kramer; Charles C Decarli; Michael W Weiner; Harry V Vinters Journal: Ann Neurol Date: 2006-12 Impact factor: 10.422
Authors: San Jung; Chris Zarow; Wendy J Mack; Ling Zheng; Harry V Vinters; William G Ellis; Scott A Lyness; Helena C Chui Journal: Arch Neurol Date: 2012-07
Authors: Thomas G Beach; Jeffrey R Wilson; Lucia I Sue; Amanda Newell; Marissa Poston; Raquel Cisneros; Yoga Pandya; Chera Esh; Donald J Connor; Marwan Sabbagh; Douglas G Walker; Alex E Roher Journal: Acta Neuropathol Date: 2006-09-20 Impact factor: 17.088
Authors: Mekala R Raman; Gregory M Preboske; Scott A Przybelski; Jeffrey L Gunter; Matthew L Senjem; Prashanthi Vemuri; Matthew C Murphy; Melissa E Murray; Bradley F Boeve; David S Knopman; Ronald C Petersen; Joseph E Parisi; Dennis W Dickson; Clifford R Jack; Kejal Kantarci Journal: Neurology Date: 2014-05-02 Impact factor: 9.910
Authors: Ling Zheng; Harry V Vinters; Wendy J Mack; Michael W Weiner; Helena C Chui Journal: J Cereb Blood Flow Metab Date: 2016-01 Impact factor: 6.200
Authors: Eseosa T Ighodaro; Erin L Abner; David W Fardo; Ai-Ling Lin; Yuriko Katsumata; Frederick A Schmitt; Richard J Kryscio; Gregory A Jicha; Janna H Neltner; Sarah E Monsell; Walter A Kukull; Debra K Moser; Frank Appiah; Adam D Bachstetter; Linda J Van Eldik; Peter T Nelson Journal: J Cereb Blood Flow Metab Date: 2016-01-06 Impact factor: 6.200
Authors: David W McNeal; Dieter D Brandner; Xi Gong; Nadia O Postupna; Thomas J Montine; C Dirk Keene; Stephen A Back Journal: J Neuropathol Exp Neurol Date: 2016-05-03 Impact factor: 3.685
Authors: John M Ringman; Sarah Monsell; Denise W Ng; Yan Zhou; Andy Nguyen; Giovanni Coppola; Victoria Van Berlo; Mario F Mendez; Spencer Tung; Sandra Weintraub; Marek-Marsel Mesulam; Eileen H Bigio; Darren R Gitelman; Amanda O Fisher-Hubbard; Roger L Albin; Harry V Vinters Journal: J Neuropathol Exp Neurol Date: 2016-02-17 Impact factor: 3.685