Is Hemispheric Hypoperfusion a Treatable Cause of Cognitive Impairment?
- 52 Downloads
Purpose of Review
To review the current literature that supports the notion that cerebral hemodynamic compromise from internal carotid artery stenosis may be a cause of vascular cognitive impairment that is amenable to treatment by revascularization.
Converging evidence suggests that successful carotid endarterectomy and carotid artery stenting are associated with reversal of cognitive decline in many patients with severe but asymptomatic carotid artery stenosis. Most of these findings have been derived from cohort studies and comparisons with either normal or surgical controls. Failure to find treatment benefit in a number of studies appears to have been the result of patient heterogeneity or confounding from concomitant conditions independently associated with cognitive decline, such as heart failure and other cardiovascular risk factors, or failure to establish pre-procedure hemodynamic failure.
Patients with severe carotid artery stenosis causing cerebral hemodynamic impairment may have a reversible cause of cognitive decline. None of the prior studies, however, were done in the context of a randomized clinical trial with large numbers of participants. The ongoing CREST-2 trial comparing revascularization with medical therapy versus medical therapy alone, and its associated CREST-H study determining whether cognitive decline is reversible among those with hemodynamic compromise may address this question.
KeywordsSevere carotid artery stenosis Revascularization Carotid endarterectomy Carotid artery stenting Cerebral hemodynamic impairment Cognition
This manuscript was funded in part by NIGMS 5T32 GM109780-4 (AMN), NINDS R01 NS097876 (RML, RSM, DSL), U01 NS080168 (TGB, JFM, BKL, RML), and U01 NS080165 (GH,VH). Additional support comes from NIH StrokeNet U01 NS06872 (RSM) and NIH StrokeNet U24NS107223 (RML).
Compliance with Ethical Standards
Conflict of Interest
Amani M. Norling, Randolph S. Marshall, Marykay A. Pavol, George Howard, Virginia Howard, John Huston, III, Brajesh K. Lal, Thomas G. Brott, and Ronald M. Lazar declare that they have no conflict of interest.
David Liebeskind reports being a consultant as Imaging Core Lab for Stryker and Medtronic.
Human and Animal Rights and Informed Consent
This article does not contain any studies with animal subjects performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 1.Gorelick PB, Furie KL, Iadecola C, Smith EE, Waddy SP, Lloyd-Jones DM, et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke. 2017;48(10):e284–303. https://doi.org/10.1161/STR.0000000000000148.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.de Weerd M, Greving JP, Hedblad B, Lorenz MW, Mathiesen EB, O'Leary DH, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke. 2010;41(6):1294–7. https://doi.org/10.1161/STROKEAHA.110.581058.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Savji N, Rockman CB, Skolnick AH, Guo Y, Adelman MA, Riles T, et al. Association between advanced age and vascular disease in different arterial territories: a population database of over 3.6 million subjects. J Am Coll Cardiol. 2013;61(16):1736–43. https://doi.org/10.1016/j.jacc.2013.01.054.CrossRefPubMedGoogle Scholar
- 11.de Weerd M, Greving JP, Hedblad B, Lorenz MW, Mathiesen EB, O'Leary DH, et al. Prediction of asymptomatic carotid artery stenosis in the general population: identification of high-risk groups. Stroke. 2014;45(8):2366–71. https://doi.org/10.1161/STROKEAHA.114.005145.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Tchistiakova E, Anderson ND, Greenwood CE, MacIntosh BJ. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults. Neuroimage Clin. 2014;5:36–41. https://doi.org/10.1016/j.nicl.2014.05.020.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.•• Marshall RS, Asllani I, Pavol MA, Cheung YK, Lazar RM. Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis. PLoS One. 2017;12(12):e0189727. https://doi.org/10.1371/journal.pone.0189727 This study demonstrates that cerebral hemodynamic compromise in the setting of asymptomatic carotid occlusion is associated with cortical thinning as measured by MRI arterial spin labeling. These findings provide important anatomical support for the notion that altered blood flow can alter brain structure that could potentially affect cognitive function. CrossRefPubMedPubMedCentralGoogle Scholar
- 21.De la Torre JC. Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer’s disease? Ann N Y Acad Sci. 2006.Google Scholar
- 22.Cechetti F, Pagnussat AS, Worm PV, Elsner VR, Ben J, da Costa MS, et al. Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment. Brain Res Bull. 2012;87(1):109–16. https://doi.org/10.1016/j.brainresbull.2011.10.006.CrossRefPubMedGoogle Scholar
- 25.Mathiesen EB, Waterloo K, Joakimsen O, Bakker SJ, Jacobsen EA, BØnaa KH. Reduced neuropsychological test performance in asymptomatic carotid stenosis: the Tromsø Study. Neurology. 2004;62(5):695–701. https://doi.org/10.1212/01.WNL.0000113759.80877.1F.CrossRefPubMedGoogle Scholar
- 26.Romero JR, Beiser A, Seshadri S, Benjamin EJ, Polak JF, Vasan RS, et al. Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke. 2009;40(5):1590–6. https://doi.org/10.1161/STROKEAHA.108.535245.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.•• Lal BK, Dux MC, Sikdar S, Goldstein C, Khan AA, Yokemick J, et al. Asymptomatic carotid stenosis is associated with cognitive impairment. J Vasc Surg. 2017;66(4):1083–92. https://doi.org/10.1016/j.jvs.2017.04.038 An excellent cross-sectional study of patients with asymptomatic carotid stenosis, half of whom had impaired vasomotor reactivity on transcranial Doppler. Nearly half of all patients were impaired in at least two domains of cogntiive function. Importantly, those with impaired cerebral hemodynamics had a worse overall cognitive scores and in learning/memory. CrossRefPubMedGoogle Scholar
- 42.Silvestrini M, Paolino I, Vernieri F, Pedone C, Baruffaldi R, Gobbi B, et al. Cerebral hemodynamics and cognitive performance in patients with asymptomatic carotid stenosis. Neurology. 2009;72(12):1062–8. https://doi.org/10.1212/01.wnl.0000345015.35520.52.CrossRefPubMedGoogle Scholar
- 49.Antonopoulos CN, Kakisis JD, Sfyroeras GS, Moulakakis KG, Kallinis A, Giannakopoulos T, et al. The impact of carotid artery stenting on cognitive function in patients with extracranial carotid artery stenosis. Ann Vasc Surg. 2015;29(3):457–69. https://doi.org/10.1016/j.avsg.2014.10.024.CrossRefPubMedGoogle Scholar
- 51.Mocco J, Wilson DA, Komotar RJ, Zurica J, Mack WJ, Halazun HJ, et al. Predictors of neurocognitive decline after carotid endarterectomy. Neurosurgery. 2006;58(5):844–50; discussion-50. https://doi.org/10.1227/01.NEU.0000209638.62401.7E.CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Ogasawara K, Yamadate K, Kobayashi M, Endo H, Fukuda T, Yoshida K, et al. Postoperative cerebral hyperperfusion associated with impaired cognitive function in patients undergoing carotid endarterectomy. J Neurosurg. 2005;102:38–44. https://doi.org/10.3171/jns.2005.102.1.0038.CrossRefPubMedGoogle Scholar
- 57.Tiemann L, Reidt JH, Esposito L, Sander D, Theiss W, Poppert H. Neuropsychological sequelae of carotid angioplasty with stent placement: correlation with ischemic lesions in diffusion weighted imaging. PLoS One. 2009;4(9):e7001. https://doi.org/10.1371/journal.pone.0007001.CrossRefPubMedPubMedCentralGoogle Scholar
- 58.Feliziani FT, Polidori MC, De Rango P, Mangialasche F, Monastero R, Ercolani S, et al. Cognitive performance in elderly patients undergoing carotid endarterectomy or carotid artery stenting: a twelve-month follow-up study. Cerebrovasc Dis. 2010;30(3):244–51. https://doi.org/10.1159/000319066.CrossRefPubMedGoogle Scholar
- 62.Picchetto L, Spalletta G, Casolla B, Cacciari C, Cavallari M, Fantozzi C, et al. Cognitive performance following carotid endarterectomy or stenting in asymptomatic patients with severe ICA stenosis. Cardiovasc Psychiatry Neurol. 2013;2013:342571–6. https://doi.org/10.1155/2013/342571.CrossRefPubMedPubMedCentralGoogle Scholar
- 63.Ortega G, Alvarez B, Quintana M, Yugueros X, Alvarez-Sabin J, Matas M. Asymptomatic carotid stenosis and cognitive improvement using transcervical stenting with protective flow reversal technique. Eur J Vasc Endovasc Surg. 2014;47(6):585–92. https://doi.org/10.1016/j.ejvs.2014.02.022.CrossRefPubMedGoogle Scholar
- 69.Howard VJ, Meschia JF, Lal BK, Turan TN, Roubin GS, Brown RD Jr, et al. Carotid revascularization and medical management for asymptomatic carotid stenosis: protocol of the CREST-2 clinical trials. Int J Stroke. 2017;12(7):770–8. https://doi.org/10.1177/1747493017706238.CrossRefPubMedPubMedCentralGoogle Scholar