Cerebral Amyloid Angiopathy (CAA)

1. Cerebral Amyloid Angiopathy
(CAA)
Ade Wijaya, MD – December 2017

2. Outline:
• Introduction
• Classiffication
• Epidemiology
• Pathology
• Pathophysiology
• Clinical features
• Diagnostic criteria
• Biomarkers
• Risk factors
• Treatment
• Summary

3. Introduction
• Cerebrovascular amyloid deposition
• A cause of normotensive cerebral hemorrhage in older individuals
• Close association with Alzheimer’s disease (AD)
• Important but underrecognized
Scholz W. Studien zur Pathologie der Hirngefäße II. Die drusige Entartung der Hirnarterien und Kapillaren. Z ges Neurol Psychiat. 1938;162:694–715.
Bano S, Yadav SN, Garga UC, Chaudhary V. Sporadic cerebral amyloid angiopathy: An important cause of cerebral hemorrhage in the elderly. Journal of Neurosciences in Rural Practice 2011;1:87-91.

4. Classification
Yamada M, Naiki H. Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci. 2012;51:41–78.

5. Epidemiology
• The prevalence of CAA increases with age
• Half of elderly individuals
• CAA is commonly observed in AD with a prevalence of about 80%-90%
Yamada M, Tsukagoshi H, Otomo E, Hayakawa M. Cerebral amyloid angiopathy in the aged. J Neurol.1987;234:371–376.
Masuda J, Tanaka K, Ueda K, Omae T. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. Stroke. 1988;19:205–210.
Yamada M. Risk factors for cerebral amyloid angiopathy in the elderly. Ann N Y Acad Sci. 2002;977:37–44.

6. Pathology
CAA and CAA-associated vasculopathies.
Massive amyloid deposition of amyloid
fibrils with degeneration of smooth muscle
cells in the media (A). Microaneurysmal
dilatation (arrow) with fibrinoid necrosis
(*) (B). Thickening of the intima (arrow)
and double barreling of vascular walls
(arrowheads) (C). (A, electron micrograph,
bar=1 µm; B, Congo red, original
magnification 110×; C, Congo red, original
magnification 170×).
Mandybur TI. Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol. 1986;45:79–90.
Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP., Jr Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol.1991;30:637–649.
Maeda A, Yamada M, Itoh Y, Otomo E, Hayakawa M, Miyatake T. Computer-assisted three-dimensional image analysis of cerebral amyloid angiopathy. Stroke. 1993;24:1857–1864

7. Pathophysiology
Yamada M. Predicting cerebral amyloid angiopathy-related intracerebral hemorrhages and other cerebrovascular disorders in Alzheimer's disease. Front Neurol. 2012;3:64.

8. Clinical Features
• Intracerebral hemorrhages (Symptomatic lobar intracerebral hemorrhages & Cortical
microhemorrhages)
• Cortical superficial siderosis/focal convexity subarachnoid hemorrhages
• White matter disease and cortical infarction
• Dementia
• CAA-related inflammation
Yamada, M. (2015). Cerebral Amyloid Angiopathy: Emerging Concepts. Journal of Stroke, 17(1), 17–30. http://doi.org/10.5853/jos.2015.17.1.17

9. Boston criteria were
proposed for the diagnosis of
CAA-related ICH
Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, et al.
Prevalence of superficial siderosis in patients with cerebral amyloid
angiopathy. Neurology. 2010;74:1346–1350.
Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of
cerebral amyloid angiopathy: validation of the Boston
criteria. Neurology. 2001;56:537–539.

10. Yamada, M. (2015). Cerebral Amyloid Angiopathy: Emerging Concepts. Journal of Stroke, 17(1), 17–30. http://doi.org/10.5853/jos.2015.17.1.17

11. Yamada, M. (2015). Cerebral Amyloid Angiopathy: Emerging Concepts. Journal of Stroke, 17(1), 17–30. http://doi.org/10.5853/jos.2015.17.1.17

12. Treatment
• No treatment to halt or reverse β-amyloid deposition
• Hematoma evacuation appears relatively safe in patients <75 years of age
without intraventricular extension
• Tramiprosate
• Immunosuppresants
• Corticosteroids
Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology 1996;46:1751-4.
Izumihara A, Ishihara T, Iwamoto N, Yamashita K, Ito H. Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Stroke 1999;30:29-33.
Kloppenborg RP, Richard E, Sprengers ME, Troost D, Eikelenboom P, Nederkoorn PJ. Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for
immunosuppressive treatment. J Neuroinflammation 2010;7:18.
Greenberg SM, Rosand J, Schneider AT, Creed Pettigrew L, Gandy SE, Rovner B, et al. A phase 2 study of tramiprosate for cerebral amyloid angiopathy. Alzheimer Dis Assoc Disord 2006;20:269-74.

13. Summary
• Cerebrovascular amyloid deposition
• A cause of normotensive cerebral hemorrhage in older individuals
• Close association with Alzheimer’s disease (AD)
• Elderly individuals
• No definitive treatments