Cerebral amyloid angiopathy: diagnosis and potential therapies

References

• Vinters HV. Cerebral amyloid angiopathy a critical review. Stroke. 1987;18:311–324.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Fox Z, Werring DJ, et al. Mapping the landscape of cerebral amyloid angiopathy research: an informetric analysis perspective. J Neurology, Neurosurg Psychiatry. 2016;87:252–259.
   PubMed Web of Science ®Google Scholar
• Keable A, Fenna K, Yuen HM, et al. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochimica Et Biophysica Acta Molecular Basis Disease. 2016;186:1037–1046.
   Google Scholar
• Wermer MJH, Greenberg SM. The growing clinical spectrum of cerebral amyloid angiopathy. Curr Opin Neurol. 2018;31:28–35.
   PubMed Web of Science ®Google Scholar
• Greenberg S M, Al-Shahi Salman R, Biessels, G. J, et al. Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol. 2014;13:419–428.
   PubMed Web of Science ®Google Scholar
• Greenberg SM. Cerebral amyloid angiopathy: prospects for clinical diagnosis and treatment. Neurology. 1998;51:690–694.
   PubMed Web of Science ®Google Scholar
• Banerjee G, Carare R, Cordonnier C, et al. The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. J Neurol Neurosurg Psychiatry. 2017;88:982–984.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Boulouis G, Gurol ME, et al. Emerging concepts in sporadic cerebral amyloid angiopathy. Brain. 2017;140:1829–1850.
   PubMed Web of Science ®Google Scholar
• Knudsen KA, Rosand J, Karluk D, et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56:537–539.
   PubMed Web of Science ®Google Scholar
• Van Rooden S, van der Grond J, van den Boom R, et al. Descriptive analysis of the Boston criteria applied to a Dutch-type cerebral amyloid angiopathy population. Stroke. 2009;40:3022–3027.
   PubMed Web of Science ®Google Scholar
• McCarron MO, Nicoll JA. Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage. Ann N Y Acad Sci. 2000;903:176–179.
   PubMed Web of Science ®Google Scholar
• Greenberg SM, Charidimou A. Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke. 2018;49:491–497.
   PubMed Web of Science ®Google Scholar
• Yamada M. Cerebral amyloid angiopathy: an overview. Neuropathology. 2000;20:8–22.
   PubMed Web of Science ®Google Scholar
• Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol. 2005;58:459–462.
   PubMed Web of Science ®Google Scholar
• Park JH, Seo SW, Kim C, et al. Pathogenesis of cerebral microbleeds: in vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol. 2013;73:584–593.
   PubMed Web of Science ®Google Scholar
• Cuny E, Loiseau H, Rivel J, et al. Amyloid angiopathy-related cerebellar hemorrhage. Surg Neurol. 1996;46:235–239.
   PubMedGoogle Scholar
• Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke. 2009;40:2382–2386.
   PubMed Web of Science ®Google Scholar
• Schrag M, McAuley G, Pomakian J, et al. Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a post-mortem MRI study. Acta Neuropathol. 2010;119:291–301.
   PubMed Web of Science ®Google Scholar
• Van Veluw SJ, Lauer A, Charidimou A, et al. Evolution of DWI lesions in cerebral amyloid angiopathy: evidence for ischemia. Neurology. 2017;89:2136–2142.
   PubMed Web of Science ®Google Scholar
• Soontornniyomkij V, Lynch MD, Mermash S, et al. Cerebral microinfarcts associated with severe cerebral β-amyloid angiopathy. Brain Pathol. 2010;20:459–467.
   PubMed Web of Science ®Google Scholar
• Auriel E, Westover MB, Bianchi MT, et al. Estimating total cerebral microinfarct burden from diffusion-weighted imaging. Stroke. 2015;46:2129–2135.
   PubMed Web of Science ®Google Scholar
• Gregoire SM, Charidimou A, Gadapa N, et al. Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain. 2011;134:2376–2386.
   PubMed Web of Science ®Google Scholar
• Van Rooden S, van Opstal AM, Labadie G, et al. Early magnetic resonance imaging and cognitive markers of hereditary cerebral amyloid angiopathy. Stroke. 2016;47:3041–3044.
   PubMed Web of Science ®Google Scholar
• Thanprasertsuk S, Martinez-Ramirez S, Pontes-Neto OM, et al. Posterior white matter disease distribution as a predictor of amyloid angiopathy. Neurology. 2014;83:794–800.
   PubMed Web of Science ®Google Scholar
• Chao CP, Kotsenas AL, Broderick DF. Cerebral amyloid angiopathy: CT and MR imaging findings. Radiographics. 2006;26:1517–1531.
   PubMed Web of Science ®Google Scholar
• Gray F, Dubas F, Roullet E, et al. Leukoencephalopathy in diffuse hemorrhagic cerebral amyloid angiopathy. Ann Neurol. 1985;18:54–59.
   PubMed Web of Science ®Google Scholar
• Loes DJ, Biller J, Yuh WT, et al. Leukoencephalopathy in cerebral amyloid angiopathy: MR imaging in four cases. AJNR Am J Neuroradiology. 1990;11:485–488.
   PubMed Web of Science ®Google Scholar
• Miller JH, Wardlaw JM, Lammie GA. Intracerebral haemorrhage and cerebral amyloid angiopathy: CT features with pathological correlation. Clin Radiol. 1999;54:422–429.
   PubMed Web of Science ®Google Scholar
• Wagle WA, Smith TW, Weiner M. Intracerebral hemorrhage caused by cerebral amyloid angiopathy: radiographic-pathologic correlation. AJNR Am J Neuroradiology. 1984;5:171–176.
   PubMed Web of Science ®Google Scholar
• Takeda S, Yamazaki K, Miyakawa T, et al. Subcortical hematoma caused by cerebral amyloid angiopathy: does the first evidence of hemorrhage occur in the subarachnoid space? Neuropathology. 2003;23:254–261.
   PubMed Web of Science ®Google Scholar
• Rodrigues MA, Samarasekera N, Lerpiniere C, et al. The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. Lancet Neurol. 2018;17:232–240.
   PubMed Web of Science ®Google Scholar
• Salman RA, Rodrigues M. The Edinburgh diagnostic criteria for lobar intracerebral haemorrhage associated with moderate/severe cerebral amyloid angiopathy, 2010-2016 [image]. University of Edinburgh. Centre for Clinical Brain Sciences; 2017. DOI:10.7488/ds/2262.
   Google Scholar
• Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8:165–174.
   PubMed Web of Science ®Google Scholar
• Cheng AL, Batool S, McCreary CR, et al. Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke. 2013;44:2782–2786.
   PubMed Web of Science ®Google Scholar
• Nandigam RN, Viswanathan A, Delgado P, et al. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiology. 2009;30:338–343.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Meegahage R, Fox Z, et al. Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry. 2013;84:624–629.
   PubMed Web of Science ®Google Scholar
• van Veluw SJ, Biessels GJ, Bouvy WH, et al. Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces. J Cereb Blood Flow Metab. 2016;36:576–580.
   PubMed Web of Science ®Google Scholar
• Conijn MM, Geerlings MI, Biessels GJ, et al. Cerebral microbleeds on MR imaging: comparison between 1.5 and 7T. AJNR Am J Neuroradiology. 2011;32:1043–1049.
   PubMed Web of Science ®Google Scholar
• Theysohn JM, Kraff O, Maderwald S, et al. 7 tesla MRI of microbleeds and white matter lesions as seen in vascular dementia. J Magn Reson Imaging. 2011;33:782–791.
   PubMed Web of Science ®Google Scholar
• Springer E, Dymerska B, Cardoso PL, et al. Comparison of routine brain imaging at 3 T and 7 T. Invest Radiol. 2016;51:469–482.
   PubMed Web of Science ®Google Scholar
• Harteveld AA, van der Kolk AG, Zwanenburg JJ, et al. 7-T MRI in cerebrovascular diseases: challenges to overcome and initial results. Top Magn Reson Imaging. 2016;25:89–100.
   PubMedGoogle Scholar
• Fazlollahi A, Meriaudeau F, Giancardo L, et al. Computer-aided detection of cerebral microbleeds in susceptibility-weighted imaging. Comput Med Imaging Graph. 2015;46:269–276.
   PubMed Web of Science ®Google Scholar
• van Den Heuvel TL, van der Eerden AW, Manniesing R, et al. Automated detection of cerebral microbleeds in patients with traumatic brain injury. NeuroImage Clin. 2016;12:241–251.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Farid K, Baron JC. Amyloid-PET in sporadic cerebral amyloid angiopathy: a diagnostic accuracy meta-analysis. Neurology. 2017;89:1490–1498.
   PubMed Web of Science ®Google Scholar
• Greenberg SM, Grabowski T, Gurol ME, et al. Detection of isolated cerebrovascular beta-amyloid with Pittsburgh compound B. Ann Neurol. 2008;64:587–591.
   PubMed Web of Science ®Google Scholar
• Gurol ME, Becker JA, Fotiadis P, et al. Florbetapir-PET to diagnose cerebral amyloid angiopathy: a prospective study. Neurology. 2016;87:2043–2049.
   PubMed Web of Science ®Google Scholar
• Raposo N, Planton M, Peran P, et al. Florbetapir imaging in cerebral amyloid angiopathy-related hemorrhages. Neurology. 2017;89:697–704.
   PubMed Web of Science ®Google Scholar
• Johnson KA, Gregas M, Becker JA, et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol. 2007;62:229–234.
   PubMed Web of Science ®Google Scholar
• Jia J, Cui M, Dai J, et al. 99mTc(CO)3-labeled benzothiazole derivatives preferentially bind cerebrovascular amyloid: potential use as imaging agents for cerebral amyloid angiopathy. Mol Pharm. 2015;12:2937–2946.
   PubMedGoogle Scholar
• Rutgers KS, Van Remoortere A, Van Buchem MA, et al. Differential recognition of vascular and parenchymal beta amyloid deposition. Neurobiol Aging. 2011;32:1774–1783.
   PubMed Web of Science ®Google Scholar
• Baron JC, Farid K, Dolan E, et al. Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage. J Cereb Blood Flow Metab. 2014;34:753–758.
   PubMed Web of Science ®Google Scholar
• Yu L, Boyle PA, Nag S, et al. APOE and cerebral amyloid angiopathy in community-dwelling older persons. Neurobiol Aging. 2015;36:2946–2953.
   PubMed Web of Science ®Google Scholar
• Rannikmäe K, Samarasekera N, Martînez-Gonzâlez NA, et al. Genetics of cerebral amyloid angiopathy: systematic review and meta-analysis. J Neurology, Neurosurg Psychiatry. 2013;84:901–908.
   PubMed Web of Science ®Google Scholar
• Rannikmäe K, Kalaria RN, Greenberg SM, et al. APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. J Neurology, Neurosurg Psychiatry. 2014;85:300–305.
   PubMed Web of Science ®Google Scholar
• Greenberg SM, Vonsattel JG, Segal AZ, et al. Association of apolipoprotein E ε2 vasculopathy in cerebral amyloid angiopathy. Neurology. 1998;50:961–965.
   PubMed Web of Science ®Google Scholar
• McCarron MO, Nicoll JAR, Stewart J, et al. The apolipoprotein E ε2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol. 1999;58:711–718.
   PubMed Web of Science ®Google Scholar
• Thal DR, Ghebremedhin E, Rub U, et al. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:282–293.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurology, Neurosurg Psychiatry. 2012;83:124–137.
   PubMed Web of Science ®Google Scholar
• Verbeek MM, Kremer BPH, Rikkert MO, et al. Cerebrospinal fluid amyloid β40 is decreased in cerebral amyloid angiopathy. Ann Neurol. 2009;66:245–249.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Friedrich JO, Greenberg SM, et al. Core CSF biomarker profile in cerebral amyloid angiopathy. Neurology. 2018. published online 2018 Jan 31. DOI:10.1212/wnl.0000000000005030.
   Web of Science ®Google Scholar
• Van Etten ES, Verbeek MM, van der Grond J, et al. β-amyloid in CSF: biomarker for preclinical cerebral amyloid angiopathy. Neurology. 2017;88:169–176.
   PubMed Web of Science ®Google Scholar
• Haan J, Maat-Schieman ML, van Duinen SG, et al. Co-localization of the beta/A4 and cystatin C in cortical blood vessels in Dutch, but not in Icelandic, hereditary cerebral hemorrhage with amyloidosis. Acta Neurol Scan. 1994;89:367–371.
   PubMed Web of Science ®Google Scholar
• Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15:673–684.
   PubMed Web of Science ®Google Scholar
• Scolding NJ, Joseph F, Kirby PA, et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain. 2005;128:500–515.
   PubMed Web of Science ®Google Scholar
• Eng JA, Frosch MP, Choi K, et al. Clinical manifestations of cerebral amyloid angiopathy related inflammation. Ann Neurol. 2004;55:250–256.
   PubMed Web of Science ®Google Scholar
• Salvarani C, Hunder GG, Morris JM, et al. AB-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis. Neurology. 2013;81:1596-1603ß.
   PubMed Web of Science ®Google Scholar
• Chung KK, Anderson NE, Hutchinson D, et al. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry. 2011;82:20–26.
   PubMed Web of Science ®Google Scholar
• McHugh JC, Ryan AM, Lynch T, et al. Steroid-responsive recurrent encephalopathy in a patient with cerebral amyloid angiopathy. Cerebrovasc Dis. 2007;23:66–69.
   PubMed Web of Science ®Google Scholar
• Karageorgiou E, Naasan G, Pleasure SJ, et al. Focal cerebral β-amyloid angiopathy: a distinct clinicopathologic presentation. Neurol Clin Pract. 2017;7:444–448.
   PubMedGoogle Scholar
• Salvarani C, Morris JM, Giannini C, et al. Imaging findings of cerebral amyloid angiopathy, Aβ-related angiitis (ABRA), and cerebral amyloid angiopathy-related inflammation: a single-institution 25-year experience. Medicine. 2016;95:e3613.
   PubMed Web of Science ®Google Scholar
• Ng DW, Magaki S, Terashima KH, et al. Amyloid-β-related angiitis: a report of 2 cases with unusual presentations. Hum Pathol. 2017;64:191–197.
   PubMed Web of Science ®Google Scholar
• DiFrancesco JC, Brioschi M, Brighina L, et al. Anti-Ab autoantibodies in the CSF of a patient with CAA-related inflammation: a case report. Neurology. 2011;76:842–844.
   PubMed Web of Science ®Google Scholar
• Hermann DM, Keyvani K, van de Nes J, et al. Brain reactive b-amyloid antibodies in primary CNS angiitis with cerebral amyloid angiopathy. Neurology. 2011;77:503–505.
   PubMed Web of Science ®Google Scholar
• Sperling R, Salloway S, Brooks DJ, et al. Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 2012;11:241–249.
   PubMed Web of Science ®Google Scholar
• Kinnecom C, Lev MH, Wendell L, et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology. 2007;68:1411–1416.
   PubMed Web of Science ®Google Scholar
• Reynolds A, Byrd E, Mossa-Basha M, et al. A 61-year-old woman with headaches and aphasia. Neurohospitalist. 2015;5:245-250.
   Google Scholar
• PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033–1041.
   PubMed Web of Science ®Google Scholar
• Arima H, Tzourio C, Anderson C, et al. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010;41:394–396.
   PubMed Web of Science ®Google Scholar
• Biffi A, Anderson CD, Battey TW, et al. Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA. 2015;314:904–912.
   PubMed Web of Science ®Google Scholar
• Amarenco P, Bogousslavsky J, Callahan A III, et al. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–559.
   PubMed Web of Science ®Google Scholar
• Westover MB, Bianchi MT, Eckman MH, et al. Statin use following intracerebral hemorrhage. Arch Neurol. 2011;68:573–579.
   PubMedGoogle Scholar
• Biffi A, Devan WJ, Anderson CD, et al. Statin use and outcome after intracerebral hemorrhage. Neurology. 2011;76:1581–1588.
   PubMed Web of Science ®Google Scholar
• McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43:2149–2156.
   PubMed Web of Science ®Google Scholar
• Vernooij MW, Haag MD, van der Lugt A, et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol. 2009;66:714–720.
   PubMedGoogle Scholar
• Wilson D, Charidimou A, Ambler G, et al. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: a meta-analysis. Neurology. 2016;87:1501–1510.
   PubMed Web of Science ®Google Scholar
• Biffi A, Halpin A, Towfighi A, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75:693–698.
   PubMed Web of Science ®Google Scholar
• Van Etten ES, Auriel E, Haley KE, et al. Incidence of symptomatic hemorrhage in patient with lobar microbleeds. Stroke. 2014;45:2280–2285.
   PubMed Web of Science ®Google Scholar
• Shoamanesh A, Charidimou A, Sharma M, et al. Should patients with ischemic stroke or transient ischemic attack with atrial fibrillation and microbleeds be anticoagulated? Stroke. 2017;48:3408–3412.
   PubMed Web of Science ®Google Scholar
• Lee S-H, Ryu W-S, Roh J-K. Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage. Neurology. 2009;72:171–176.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Boulouis G, Shams S, et al. for the International META-MICROBLEEDS Initiative. Intracerebral haemorrhage risk in microbleed-positive ischaemic stroke patients with atrial fibrillation: preliminary meta-analysis of cohorts and anticoagulation decision schema. J Neurol Sci. 2017;378:102–109.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Karayiannis C, Song T-J, et al. Brain microbleeds, anticoagulation, and hemorrhage risk: meta-analysis in stroke patients with AF. Neurology. 2017;89:2317–2326.
   PubMed Web of Science ®Google Scholar
• Eckman MH, Rosand J, Knudsen KA, et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34:1710–1716.
   PubMed Web of Science ®Google Scholar
• Saito T, Kawamura Y, Sato N, et al. Non-vitamin K antagonist oral anticoagulants do not increase cerebral microbleeds. J Stroke Cerebrovasc Dis. 2015;24:1373–1377.
   PubMed Web of Science ®Google Scholar
• [cited 2018 Apr 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT02565693?term=APACHE-AF&rank=1
   Google Scholar
• [cited 2018 Apr 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT03153150?term=SOSTART&rank=1
   Google Scholar
• [cited 2018 Apr 26]. Available from: http://www.lin-bcn.com/new-h2020-project-prestige/
   Google Scholar
• Horstmann S, Zugck C, Krumsdorf U, et al. Left atrial appendage occlusion in atrial fibrillation after intracranial hemorrhage. Neurology. 2014;82:135–138.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Peeters AP, Jager R, et al. Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy. Neurology. 2013;81:1666–1673.
   PubMed Web of Science ®Google Scholar
• Charidimou A, Boulouis G, Roongpiboonsopit D, et al. Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: a prospective study. Neurology. 2017;89:2128–2135.
   PubMed Web of Science ®Google Scholar
• [cited 2018 Feb 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT00056238?cond=Cerebral+Amyloid+Angiopathy&rank=6
   Google Scholar
• La Porte SL, Bollini SS, Lanz TA, et al. Structural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer’s disease. J Mol Biol. 2012;421:525–536.
   PubMed Web of Science ®Google Scholar
• [cited 2018 Feb 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT01821118?cond=Cerebral+Amyloid+Angiopathy&rank=1
   Google Scholar
• [cited 2018 Feb 5]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01821118?sect=Xa987056&term=ponezumab&rank=3&view=results#outcome4
   Google Scholar