The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Abstract

Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer's disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer's and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

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     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.

     Not in our library10.1212/wnl.0000000000000732

109. 109.

     Samuraki M, Matsunari I, Yoshita M, et al Cerebral amyloid angiopathy-related microbleeds correlate with glucose metabolism and brain volume in Alzheimer’s disease. J Alzheimers Dis 2015;48:517–28.

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110. 110.

     Charidimou A, Martinez-Ramirez S, Shoamanesh A, et al Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease phenotypes. Neurology 2015;84:1206–12.

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111. 111.

     Yu L, Boyle PA, Nag S, et al APOE and cerebral amyloid angiopathy in community-dwelling older persons. Neurobiol Aging 2015;36:2946–53.

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112. 112.

     Rannikmäe K, Kalaria RN, Greenberg SM, et al APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. J Neurol Neurosurg Psychiatry 2014;85:300–5.

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113. 113.

     Charidimou A, Peeters A, Fox Z, et al Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis. Stroke 2012;43:2324–30.

     Not in our library10.1161/strokeaha.112.657759

114. 114.

     Ni J, Auriel E, Jindal J, et al The characteristics of superficial siderosis and convexity subarachnoid hemorrhage and clinical relevance in suspected cerebral amyloid angiopathy. Cerebrovasc Dis 2015;39(5-6):278–86.

     Not in our library10.1159/000381223

115. 115.

     Calviere L, Cuvinciuc V, Raposo N, et al Acute convexity subarachnoid hemorrhage related to cerebral amyloid angiopathy: clinicoradiological features and outcome. J Stroke Cerebrovasc Dis 2016;25:1009–16.

     Not in our library10.1016/j.jstrokecerebrovasdis.2015.11.010

116. 116.

     Apoil M, Cogez J, Dubuc L, et al Focal cortical subarachnoid hemorrhage revealed by recurrent paresthesias: a clinico-radiological syndrome strongly associated with cerebral amyloid angiopathy. Cerebrovasc Dis 2013;36:139–44.

     Not in our library10.1159/000353676

117. 117.
     Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex · 2010

     No notice
118. 118.

     Leng LZ, Fink ME, Iadecola C Spreading depolarization: a possible new culprit in the delayed cerebral ischemia of subarachnoid hemorrhage. Arch Neurol 2011;68:31–6.

     Not in our library10.1001/archneurol.2010.226

119. 119.

     Sánchez-Porras R, Zheng Z, Santos E, et al The role of spreading depolarization in subarachnoid hemorrhage. Eur J Neurol 2013;20:1121–7.

     Not in our library10.1111/ene.12139

120. 120.

     Viswanathan A, Rakich SM, Engel C, et al Antiplatelet use after intracerebral hemorrhage. Neurology 2006;66:206–9.

     Not in our library10.1212/01.wnl.0000194267.09060.77

121. 121.

     Poon MT, Fonville AF, Al-Shahi Salman R Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014;85:660–7.

     Not in our library10.1136/jnnp-2013-306476

122. 122.

     Claassen DO, Kazemi N, Zubkov AY, et al Restarting anticoagulation therapy after warfarin-associated intracerebral hemorrhage. Arch Neurol 2008;65:1313–8.

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123. 123.

     Majeed A, Kim Y-K, Roberts RS, et al Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke 2010;41:2860–6.

     Not in our library10.1161/strokeaha.110.593087

124. 124.

     Yung D, Kapral MK, Asllani E, et al Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: the best practice for reinitiating anticoagulation therapy after intracranial bleeding (BRAIN) study. Can J Cardiol 2012;28:33–9.

     Not in our library10.1016/j.cjca.2011.10.002

125. 125.

     Poli D, Antonucci E, Dentali F, et al Recurrence of ICH after resumption of anticoagulation with VK antagonists: chirone study. Neurology 2014;82:1020–6.

     Not in our library10.1212/wnl.0000000000000245

126. 126.

     Nielsen PB, Larsen TB, Skjøth F, et al Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation 2015;132:517–25.

     Not in our library10.1161/circulationaha.115.015735

127. 127.

     Pennlert J, Overholser R, Asplund K, et al Optimal timing of anticoagulant treatment after intracerebral hemorrhage in patients with atrial fibrillation. Stroke 2017;48:314–20.

     Not in our library10.1161/strokeaha.116.014643

128. 128.

     Nielsen PB, Larsen TB, Skjøth F, et al Outcomes associated with resuming warfarin treatment after hemorrhagic stroke or traumatic intracranial hemorrhage in patients with atrial fibrillation. JAMA Intern Med 2017;177:563–70.

     Not in our library10.1001/jamainternmed.2016.9369

129. 129.

     Murthy SB, Gupta A, Merkler AE, et al Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-Analysis. Stroke 2017;48:1594–600.

     Not in our library10.1161/strokeaha.116.016327

130. 130.

     Chao TF, Liu CJ, Chen SJ, et al Statins and the risk of dementia in patients with atrial fibrillation: a nationwide population-based cohort study. Int J Cardiol 2015;196:91–7.

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131. 131.

     Kuramatsu JB, Gerner ST, Schellinger PD, et al Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015;313:824–36.

     Not in our library10.1001/jama.2015.0846

132. 132.

     Samarasekera N, Fonville A, Lerpiniere C, et al Influence of intracerebral hemorrhage Location on incidence, characteristics, and outcome: population-based study. Stroke 2015;46:361–8.

     Not in our library10.1161/strokeaha.114.007953

133. 133.

     Hemphill JC, Greenberg SM, Anderson CS, et al Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46:2032–60.

     Not in our library10.1161/str.0000000000000069

134. 134.

     Kirchhof P, Benussi S, Kotecha D, et al 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg 2016;50:e1–88.

     Not in our library10.1093/ejcts/ezw313

135. 135.

     Ruff CT, Giugliano RP, Braunwald E, et al Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955–62.

     Not in our library10.1016/s0140-6736(13)62343-0

136. 136.

     Connolly SJ, Eikelboom J, Joyner C, et al Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17.

     Not in our library10.1056/nejmoa1007432

137. 137.

     O’Donnell MJ, Eikelboom JW, Yusuf S, et al Effect of apixaban on brain infarction and microbleeds: averroes-MRI assessment study. Am Heart J 2016;178:145–50.

     Not in our library10.1016/j.ahj.2016.03.019

138. 138.

     van Nieuwenhuizen KM, van der Worp HB, Algra A, et al Apixaban versus antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with atrial fibrillation (APACHE-AF): study protocol for a randomised controlled trial. Trials 2015;16:393

     Not in our library10.1186/s13063-015-0898-4

139. 139.
     Use of MRI for risk stratification in anticoagulation decision making in Atrial Fibrillation: promising, but more data are needed for a robust algorithm · 2014

     Not checked
140. 140.

     Akoudad S, Portegies ML, Koudstaal PJ, et al Cerebral microbleeds are associated with an increased risk of stroke: the rotterdam study. Circulation 2015;132:509–16.

     Not in our library10.1161/circulationaha.115.016261

141. 141.

     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;87:1501–10.

     Not in our library10.1212/wnl.0000000000003183

142. 142.

     Smith EE, Saposnik G, Biessels GJ, et al Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2017;48:e44–71.

     Not in our library10.1161/str.0000000000000116

143. 143.

     Eckman MH, Wong LK, Soo YO, et al Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help? Stroke 2008;39:3308–15.

     Not in our library10.1161/strokeaha.108.523159

144. 144.

     Charidimou A, Wilson D, Shakeshaft C, et al The clinical relevance of microbleeds in stroke study (CROMIS-2): rationale, design, and methods. Int J Stroke 2015;10:155–61.

     Not in our library10.1111/ijs.12569

145. 145.

     Worldwide collaboration in the Microbleeds International Collaborative Network. The Lancet. Neurology 2016;15:1113–4.

     Not in our library10.1016/s1474-4422(16)30213-7

146. 146.

     Goldstein LB, Amarenco P, Szarek M, et al Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 2008;70(24 Pt 2):2364–70.

     Not in our library10.1212/01.wnl.0000296277.63350.77

147. 147.

     Amarenco P, Bogousslavsky J, Callahan A, et al High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–59.

     Not in our library10.1056/nejmoa061894

148. 148.

     Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.

     Not in our library10.1016/s0140-6736(02)09327-3

149. 149.

     Vergouwen MDI, de Haan RJ, Vermeulen M, et al Statin treatment and the occurrence of hemorrhagic stroke in patients with a history of cerebrovascular disease. Stroke 2008;39:497–502.

     Not in our library10.1161/strokeaha.107.488791

150. 150.

     Goldstein LB, Nederkoorn PJ Statins and poststroke intracerebral hemorrhage: concern but increasing reassurance. Neurology 2016;86:1570–1.

     Not in our library10.1212/wnl.0000000000002618

151. 151.

     Lauer A, Greenberg SM, Gurol ME Statins in intracerebral hemorrhage. Curr Atheroscler Rep 2015;17:46

     Not in our library10.1007/s11883-015-0526-5

152. 152.

     Flint AC, Conell C, Rao VA, et al Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition. JAMA Neurol 2014;71:1364–71.

     Not in our library10.1001/jamaneurol.2014.2124

153. 153.

     Tapia Pérez JH, Yildiz OC, Schneider T, et al Meta-analysis of statin use for the acute therapy of spontaneous intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2015;24:2521–6.

     Not in our library10.1016/j.jstrokecerebrovasdis.2015.06.036

154. 154.

     Jung JM, Choi JY, Kim HJ, et al Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta-analysis. Int J Stroke 2015;10:10–17.

     Not in our library10.1111/ijs.12624

155. 155.

     Winkler J, Shoup JP, Czap A, et al Long-term improvement in outcome after intracerebral hemorrhage in patients treated with statins. J Stroke Cerebrovasc Dis 2013;22:e541–5.

     Not in our library10.1016/j.jstrokecerebrovasdis.2013.06.015

156. 156.

     Pan YS, Jing J, Wang YL, et al Use of statin during hospitalization improves the outcome after intracerebral hemorrhage. CNS Neurosci Ther 2014;20:548–55.

     Not in our library10.1111/cns.12274

157. 157.

     Chen PS, Cheng CL, Chang YC, et al Early statin therapy in patients with acute intracerebral hemorrhage without prior statin use. Eur J Neurol 2015;22:773–80.

     Not in our library10.1111/ene.12649

158. 158.

     Chen PS, Cheng CL, Kao Yang YH, et al Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack. Acta Neurol Scand 2014;129:41–8.

     Not in our library10.1111/ane.12143

159. 159.

     Dowlatshahi D, Demchuk AM, Fang J, et al Association of statins and statin discontinuation with poor outcome and survival after intracerebral hemorrhage. Stroke 2012;43:1518–23.

     Not in our library10.1161/strokeaha.111.645978

160. 160.

     Woo D, Deka R, Falcone GJ, et al Apolipoprotein E, statins, and risk of intracerebral hemorrhage. Stroke 2013;44:3013–7.

     Not in our library10.1161/strokeaha.113.001304

161. 161.

     Pezzini A, Grassi M, Iacoviello L, et al Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) Investigators. Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on cerebral haemorrhage in Italy (MUCH-Italy). J Neurol Neurosurg Psychiatry 2016;87:924–9.

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162. 162.

     Westover MB, Bianchi MT, Eckman MH, et al Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol 2011;68:573–9.

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163. 163.

     Haussen DC, Henninger N, Kumar S, et al Statin use and microbleeds in patients with spontaneous intracerebral hemorrhage. Stroke 2012;43:2677–81.

     Not in our library10.1161/strokeaha.112.657486

164. 164.

     Romero JR, Preis SR, Beiser A, et al Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke 2014;45:1492–4.

     Not in our library10.1161/strokeaha.114.004130

165. 165.

     A phase 2, Randomized, Double Blind Placebo Controlled Trial to evaluate the safety, tolerability, Pharmacokinetics and Efficacy of Pf-04360365 (Ponezumab) In adult subjects with Probable Cerebral Amyloid Angiopathy. http://clinicaltrials.gov/show/NCT01821118 (accessed 4 Sep 2016).

     Not in our library

166. 166.

     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(4-5):525–36.

     Not in our library10.1016/j.jmb.2011.11.047

167. 167.

     Burstein AH, Zhao Q, Ross J, et al Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol 2013;36:8–13.

     Not in our library10.1097/wnf.0b013e318279bcfa

168. 168.

     Landen JW, Zhao Q, Cohen S, et al Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol 2013;36:14–23.

     Not in our library10.1097/wnf.0b013e31827db49b

169. 169.

     Bales KR, O’Neill SM, Pozdnyakov N, et al Passive immunotherapy targeting amyloid-β reduces cerebral amyloid angiopathy and improves vascular reactivity. Brain 2016;139(Pt 2):563–77.

     Not in our library10.1093/brain/awv313

170. 170.

     Sperling RA, Jack CR, Black SE, et al Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 2011;7:367–85.

     Not in our library10.1016/j.jalz.2011.05.2351

171. 171.

     Al-Shawi R, Tennent GA, Millar DJ, et al Pharmacological removal of serum amyloid P component from intracerebral plaques and cerebrovascular Aβ amyloid deposits in vivo. Open Biol 2016;6:150202

     Not in our library10.1098/rsob.150202

172. 172.

     Arima H, Tzourio C, Anderson C, et al PROGRESS Collaborative Group. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the progress trial. Stroke 2010;41:394–6.

     Not in our library10.1161/strokeaha.109.563932

173. 173.

     Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, et al Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke 2013;44:2995–9.

     Not in our library10.1161/strokeaha.113.002545

174. 174.

     Yamaguchi Y, Wada M, Sato H, et al Impact of ambulatory blood pressure variability on cerebral small vessel disease progression and cognitive decline in community-based elderly Japanese. Am J Hypertens 2014;27:1257–67.

     Not in our library10.1093/ajh/hpu045

Cited by papers we hold 3

• Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease · 2023
  No notice
• sTWEAK is a leukoaraiosis biomarker associated with neurovascular angiopathy · 2022
  Not checked
• Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease · 2018
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.