Jose Gutierrez1, Lawrence Honig2, Mitchell S V Elkind2, Jay P Mohr2, James Goldman2, Andrew J Dwork2, Susan Morgello2, Randolph S Marshall2. 1. From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY. jg3233@cumc.columbia.edu. 2. From the Departments of Neurology (J.G., L.H., M.S.V.E., J.P.M.) and Psychiatry (A.J.D.), College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health (M.S.V.E., R.S.M.), and Department of Pathology and Cell Biology (J.G., A.J.D.), Columbia University; Division of Molecular Imaging and Neuropathology (A.J.D.), New York State Psychiatric Institute; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract
OBJECTIVE: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). METHODS: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. RESULTS: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). CONCLUSIONS: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD.
OBJECTIVE: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). METHODS: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. RESULTS: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). CONCLUSIONS: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD.
Authors: Timothy M Hughes; Lewis H Kuller; Emma J M Barinas-Mitchell; Rachel H Mackey; Eric M McDade; William E Klunk; Howard J Aizenstein; Ann D Cohen; Beth E Snitz; Chester A Mathis; Steven T Dekosky; Oscar L Lopez Journal: Neurology Date: 2013-10-16 Impact factor: 9.910
Authors: Heiko Braak; Irina Alafuzoff; Thomas Arzberger; Hans Kretzschmar; Kelly Del Tredici Journal: Acta Neuropathol Date: 2006-08-12 Impact factor: 17.088
Authors: Steven D Shapiro; James Goldman; Susan Morgello; Lawrence Honig; Mitchell S V Elkind; Randolph S Marshall; Jay P Mohr; Jose Gutierrez Journal: Cardiovasc Pathol Date: 2018-10-12 Impact factor: 2.185
Authors: William Roth; Susan Morgello; James Goldman; Jay P Mohr; Mitchell S V Elkind; Randolph S Marshall; Jose Gutierrez Journal: Stroke Date: 2017-02-14 Impact factor: 7.914
Authors: Li Chen; Jie Sun; Daniel S Hippe; Niranjan Balu; Quan Yuan; Isabelle Yuan; Xihai Zhao; Rui Li; Le He; Thomas S Hatsukami; Jenq-Neng Hwang; Chun Yuan Journal: Neurobiol Aging Date: 2019-03-28 Impact factor: 4.673
Authors: Jose Gutierrez; Erin Kulick; Yeseon Park Moon; Chuanhui Dong; Ken Cheung; Bagci Ahmet; Yaakov Stern; Noam Alperin; Tatjana Rundek; Ralph L Sacco; Clinton B Wright; Mitchell S V Elkind Journal: J Int Neuropsychol Soc Date: 2017-11-23 Impact factor: 2.892
Authors: Jose Gutierrez; Vanessa Guzman; Farid Khasiyev; Jennifer Manly; Nicole Schupf; Howard Andrews; Richard Mayeux; Adam M Brickman Journal: Alzheimers Dement Date: 2019-03-01 Impact factor: 21.566
Authors: Jessica L Montoya; Jennifer Iudicello; Pariya L Fazeli; Suzi Hong; Michael Potter; Ronald J Ellis; Igor Grant; Scott L Letendre; David J Moore Journal: J Acquir Immune Defic Syndr Date: 2017-02-01 Impact factor: 3.731
Authors: Adele Shenoy; Andrew Dwork; Mitchell S V Elkind; Randolph Marshall; Susan Morgello; Jose Gutierrez Journal: J Virol Date: 2018-05-29 Impact factor: 5.103
Authors: Rebecca F Gottesman; Andrea L C Schneider; Yun Zhou; Josef Coresh; Edward Green; Naresh Gupta; David S Knopman; Akiva Mintz; Arman Rahmim; A Richey Sharrett; Lynne E Wagenknecht; Dean F Wong; Thomas H Mosley Journal: JAMA Date: 2017-04-11 Impact factor: 56.272