Abstract: HomeStrokeVol. 35, No. 11_suppl_1Vascular Cognitive Impairment Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBVascular Cognitive ImpairmentIntroduction Vladimir Hachinski and Costantino Iadecola Vladimir HachinskiVladimir Hachinski From the Department of Neurology, University of Western Ontario (V.H.), London, Ontario, Canada; and the Division of Neurobiology (C.I.), Weill Medical College of Cornell University and Neuroscience, New York, NY. and Costantino IadecolaCostantino Iadecola From the Department of Neurology, University of Western Ontario (V.H.), London, Ontario, Canada; and the Division of Neurobiology (C.I.), Weill Medical College of Cornell University and Neuroscience, New York, NY. Originally published30 Sep 2004https://doi.org/10.1161/01.STR.0000143237.11078.bcStroke. 2004;35:2615Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 30, 2004: Previous Version 1 One of the greatest advances in the understanding of cognitive disorders comes from the realization that Alzheimer disease (AD) and vascular cognitive impairment share common risk factors. This opens the door to a common approach to both and promises that if vascular risk factors are controlled, then not only strokes but also cognitive impairment could be prevented. It also has become evident that AD pathology and vascular lesions often coexist in the brains of the elderly. Less certain is whether the effects are additive or multiplicative.Gorelick1 reviews and categorizes systematically the different risk factors as demographic, atherosclerotic, genetic, and stroke-related. As our knowledge grows, perhaps another relevant category will be identified, namely protective factors. Not all brains are created equal, varying both in their capacity and in their resistance to injury. Moreover, the brain is molded by experience and environment. We are just beginning to glimpse what strengthens and weakens the brain's natural resilience.Amyloid angiopathy has long been recognized in association with cognitive impairment, especially AD. What was not realized is that amyloidal deposition is strongly associated with white matter changes and a host of vascular alterations. Greenberg et al2 emphasize that microcirculatory changes long precede the familiar catastrophic hemorrhage, sometimes heralded by small warning leaks. Understanding the mechanisms of amyloid deposition and clearance may hold the key to successful interventions.Deave et al3 describe the important and interactive roles of the receptor for advanced glycation end products and low-density lipoprotein receptor-related protein-1 in the trafficking of β-amyloid across the blood–brain barrier. Their findings implicate these vascular receptors in the control the homeostasis of Aβ in brain, highlighting a previously unrecognized role of cerebral blood vessels in "neurodegenerative" pathologies characterized by β-amyloid accumulation. Thus, receptor for advanced glycation end products receptors and low-density lipoprotein receptor-related protein-1 emerge as potential therapeutic targets to enhance β-amyloid clearance from the brain in patients with AD and other conditions associated with cerebral amyloid accumulation.Three decades ago, atherosclerosis allegedly explained most cognitive decline in the elderly. After being eclipsed by AD as a cause of cognitive impairment, atherosclerosis has regained prominence as a possible culprit in AD itself, as Roher et al4 argue. Although the association of AD and atherosclerosis is clear, their interaction is not. Ischemia and infarction are not the only mechanism through which atherosclerosis can act. It may be that some of the risk factors for atherosclerosis such as hypertension may cause damage through other mechanisms, such as protein leakage into the brain and inflammation. Moreover, both AD change and atherosclerosis may be enhanced by a common factor, such as the presence of the lipoprotein E (ε) 4/4 allele.Whatever the ultimate explanation may be, the fact remains that AD and atherosclerosis have common risk factors and, hence in principle, the potential for similar treatments and prevention.FootnotesCorrespondence to Dr Vladimir Hachinski, Editor-in-Chief, Stroke, UWO Research Park, 100 Collip Circle, Suite 116, London, Ontario, Canada, N6G 4X8. E-mail [email protected]References1 Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke. 2004; 35 [suppl I]: 2620–2622.LinkGoogle Scholar2 Greenberg SM, Gurol E, Rosand J, Smith EE. Amyloid angiopathy-related vascular cognitive impairment. Stroke. 2004; 35 [suppl I]: 2616–2619.LinkGoogle Scholar3 Deane R, Wu Z, Zlokovic BV. RAGE (yin) versus LRP (yang) balance regulates Alzheimer amyloid B-peptide clearance via transport across the blood-brain barrier. Stroke. 2004; 35 [suppl I]: 2628–2631.LinkGoogle Scholar4 Roher AE, Esh C, Rahman A, Kokjohn T, Beach T. Atherosclerosis of cerebral arteries in Alzheimer disease. Stroke. 2004; 35 [suppl I]: 2623–2627.LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Marmarelis V, Shin D and Zhang R (2021) The Dynamic Relationship Between Cortical Oxygenation and End-Tidal CO2 Transient Changes Is Impaired in Mild Cognitive Impairment Patients, Frontiers in Physiology, 10.3389/fphys.2021.772456, 12 Marmarelis V, Shin D and Zhang R Dysregulation of CO2-Driven Heart-Rate Chemoreflex Is Related Closely to Impaired CO2 Dynamic Vasomotor Reactivity in Mild Cognitive Impairment Patients, Journal of Alzheimer's Disease, 10.3233/JAD-191238, 75:3, (855-870) Marmarelis V, Shin D, Tarumi T and Zhang R Comparison of Model-Based Indices of Cerebral Autoregulation and Vasomotor Reactivity Using Transcranial Doppler versus Near-Infrared Spectroscopy in Patients with Amnestic Mild Cognitive Impairment, Journal of Alzheimer's Disease, 10.3233/JAD-161004, 56:1, (89-105) Marmarelis V, Shin D, Orme M and Zhang R (2013) Model-based Quantification of Cerebral Hemodynamics as a Physiomarker for Alzheimer's Disease?, Annals of Biomedical Engineering, 10.1007/s10439-013-0837-z, 41:11, (2296-2317), Online publication date: 1-Nov-2013. Huckman M (2016) Imaging Dementing Illnesses, The Neuroradiology Journal, 10.1177/197140090601900405, 19:4, (441-451), Online publication date: 1-Aug-2006. Silvestrini M, Pasqualetti P, Baruffaldi R, Bartolini M, Handouk Y, Matteis M, Moffa F, Provinciali L and Vernieri F (2006) Cerebrovascular Reactivity and Cognitive Decline in Patients With Alzheimer Disease, Stroke, 37:4, (1010-1015), Online publication date: 1-Apr-2006. Antoine V and Rigaud A (2006) Maladie d'Alzheimer : prendre en compte les facteurs de risque et pathologies cardiovasculaires, La Revue de Médecine Interne, 10.1016/j.revmed.2005.04.037, 27:1, (21-31), Online publication date: 1-Jan-2006. November 2004Vol 35, Issue 11_suppl_1 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000143237.11078.bc Manuscript receivedJuly 20, 2004Manuscript acceptedAugust 5, 2004Originally publishedSeptember 30, 2004 PDF download Advertisement