Cerebral amyloid angiopathy
Updates to Article Attributes
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the accumulation of cerebral amyloid-β (Aβ) in the media of leptomeningeal and cortical vessels of the brain. The resultant vascular fragility tends to manifest in normotensive elderly patients as lobar intracerebral haemorrhage. It is, along with Alzheimer disease, a common cerebral amyloid deposition disease.
Epidemiology
Cerebral amyloid angiopathy can be divided into spontaneous (sporadic) and inherited forms.
Spontaneous CAA
Cerebral amyloid angiopathy if a frequent incidental finding, found on screening gradient imaging in up to 16% of asymptomatic elderly patients 4. Autopsy studies have found a prevalence of approximately 5-9% in patients between 60 and 69 years, and 43-58% in patients over the age of 90 4.
Autopsy of patients who have evidence of Alzheimer disease have found CAA in the vast majority of cases (90%). This rate is still high (20-40%) in non-demented elderly individuals 14.
Importantly it is usually notassociated with systemic amyloidosis.
Inherited CAA
Inherited cerebral amyloid angiopathy is rare, and encountered as an autosomal dominant condition 14. It mainly differs from spontaneous forms in earlier age of onset, typically in middle to late middle age 14.
Clinical presentation
Symptomatic clinical presentation is usually with an intracerebral haemorrhage, found in 40% of autopsy proven cases of CAA 1. This is often in the form of microhaemorrhages or of lobar haemorrhages. Of all patients with cerebral haemorrhage, CAA is found in 4-10% of cases 2. Vessel damage can also result in ischaemic leukoencephalopathy 1.
Uncommonly an inflammatory reaction may be incited and patients can present in a more subacute fashion with declining cognitive performance, seizures, headache and stroke like episodes (without haemorrhage) 11. This known as cerebral amyloid angiopathy-related inflammation and is discussed separately.
Occasionally mass like lesions, known as cerebral amyloidoma, have been reported 3,14 (not to be confused with cerebral amyloidosis seen in patients with systemic amyloidosis).
The Boston criteria 7 is a combination of clinical, radiographic and pathological criteria which are used to assess the probability of CAA.
Pathology
CAA is characterised by the deposition of ß-amyloid (Aß-40) in the media and adventitia of small and medium sized arteries of the cerebral cortex and leptomeninges 4. This is associated with fibrinoid degeneration, and microaneurysm formation 1. Amyloid is an eosinophilic, insoluble protein, located in the extra-cellular space, and stains with Congo red yielding apple green birefringence when viewed with polarized light 3. It is important to note that amyloid deposition is also encountered in other clinical scenarios including spongiform encephalitis 1.
Associations
-
Alzheimer's disease
- pathological CAA changes are seen in ~80% of those with Alzheimer's disease (Aß-42) 5-13
- ~40% of those with CAA have Alzheimer's dementia type symptoms
Radiographic features
Findings reflect the various manifestations of the disease:
-
microhaemorrhages
- not seen on CT
- small focal regions of signal drop out best seen on T2* sequences (gradient echo, echo-planar, SWI) as regions of blooming 12
- may be difficult to see on conventional T1 and T2 sequences 4
- tend to be subcortical (grey-white matter junction)
- they spare the basal ganglia (c.f. hypertensive microhaemorrhages) 4, 14
-
cerebral haemorrhage
- usually superficial (lobar)
- appearance will vary according to age of bleed (see: blood on MRI)
-
siderosis
- may be seen in up to 60% of patients 9
- leukoencephalopathy
- CT: diffuse low density of the white matter with mass effect
- MR: diffuse white matter hyperintensity on T2 weighted scans 1,6
- may mimic mass3 or gliomatosi
- responds to steroids
Radiographic features of cerebral amyloid angiopathy related inflammation are discussed separately.
Differential diagnosis
-
hypertensive microangiopathy
- typically in basal ganglia, pons and cerebellum
-
multiple cavernoma syndrome
- random distribution
- random size
- often characteristic cavernous malformations can be identified
-
haemorrhagic metastases (e.g. melanoma)
- usually larger
- enhancing
-
neurocysticercosis
- nodular calcified stage
- random
- prior radiotherapy
- very similar appearance (similar pathophysiology)
- distribution related to treatment field
-<p><strong>Cerebral amyloid angiopathy (CAA)</strong> is a cerebrovascular disorder caused by the accumulation of cerebral amyloid-β (Aβ) in the media of leptomeningeal and cortical vessels of the brain. The resultant vascular fragility tends to manifest in normotensive elderly patients as <a href="/articles/lobar-haemorrhage">lobar intracerebral haemorrhage</a>. It is, along with <a title="Alzheimer disease" href="/articles/alzheimer-disease-1">Alzheimer disease</a>, a common <a href="/articles/cerebral-amyloid-deposition-diseases">cerebral amyloid deposition disease</a>.</p><h4>Epidemiology </h4><p>Cerebral amyloid angiopathy can be divided into spontaneous (sporadic) and inherited forms. </p><h5>Spontaneous CAA</h5><p>Cerebral amyloid angiopathy if a frequent incidental finding, found on screening gradient imaging in up to 16% of asymptomatic elderly patients <sup>4</sup>. Autopsy studies have found a prevalence of approximately 5-9% in patients between 60 and 69 years, and 43-58% in patients over the age of 90 <sup>4</sup>.</p><p>Autopsy of patients who have evidence of Alzheimer disease have found CAA in the vast majority of cases (90%). This rate is still high (20-40%) in non-demented elderly individuals <sup>14</sup>. </p><p>Importantly it is usually not<strong> </strong>associated with systemic <a href="/articles/amyloidosis">amyloidosis</a>.</p><h5>Inherited CAA</h5><p>Inherited cerebral amyloid angiopathy is rare, and encountered as an autosomal dominant condition <sup>14</sup>. It mainly differs from spontaneous forms in earlier age of onset, typically in middle to late middle age <sup>14</sup>.</p><h4>Clinical presentation</h4><p>Symptomatic clinical presentation is usually with an <a href="/articles/intracerebral-haemorrhage">intracerebral haemorrhage</a>, found in 40% of autopsy proven cases of CAA <sup>1</sup>. This is often in the form of <a href="/articles/cerebral-microhaemorrhage">microhaemorrhages</a> or of <a href="/articles/lobar-haemorrhage">lobar haemorrhages</a>. Of all patients with cerebral haemorrhage, CAA is found in 4-10% of cases <sup>2</sup>. Vessel damage can also result in ischaemic leukoencephalopathy <sup>1</sup>.</p><p>Uncommonly an inflammatory reaction may be incited and patients can present in a more subacute fashion with declining cognitive performance, seizures, headache and stroke like episodes (without haemorrhage) <sup>11</sup>. This known as <a href="/articles/cerebral-amyloid-angiopathy-related-inflammation">cerebral amyloid angiopathy-related inflammation</a> and is discussed separately. </p><p>Occasionally mass like lesions, known as <a href="/articles/cerebral-amyloidoma">cerebral amyloidoma</a>, have been reported <sup>3,14</sup> (not to be confused with <a href="/articles/cerebral-amyloidosis">cerebral amyloidosis</a> seen in patients with systemic amyloidosis). </p><p>The <a href="/articles/boston-criteria">Boston criteria</a> <sup>7 </sup>is a combination of clinical, radiographic and pathological criteria which are used to assess the probability of CAA.</p><h4>Pathology</h4><p>CAA is characterised by the deposition of ß-amyloid (Aß-40) in the media and adventitia of small and medium sized arteries of the cerebral cortex and leptomeninges <sup>4</sup>. This is associated with fibrinoid degeneration, and microaneurysm formation <sup>1</sup>. Amyloid is an eosinophilic, insoluble protein, located in the extra-cellular space, and stains with Congo red yielding apple green birefringence when viewed with polarized light <sup>3</sup>. It is important to note that amyloid deposition is also encountered in other clinical scenarios including <a href="/articles/spongiform-encephalitis">spongiform encephalitis</a> <sup>1</sup>.</p><h5>Associations</h5><ul><li>- +<p><strong>Cerebral amyloid angiopathy (CAA)</strong> is a cerebrovascular disorder caused by the accumulation of cerebral amyloid-β (Aβ) in the media of leptomeningeal and cortical vessels of the brain. The resultant vascular fragility tends to manifest in normotensive elderly patients as <a href="/articles/lobar-haemorrhage">lobar intracerebral haemorrhage</a>. It is, along with <a href="/articles/alzheimer-disease-1">Alzheimer disease</a>, a common <a href="/articles/cerebral-amyloid-deposition-diseases">cerebral amyloid deposition disease</a>.</p><h4>Epidemiology </h4><p>Cerebral amyloid angiopathy can be divided into spontaneous (sporadic) and inherited forms. </p><h5>Spontaneous CAA</h5><p>Cerebral amyloid angiopathy if a frequent incidental finding, found on screening gradient imaging in up to 16% of asymptomatic elderly patients <sup>4</sup>. Autopsy studies have found a prevalence of approximately 5-9% in patients between 60 and 69 years, and 43-58% in patients over the age of 90 <sup>4</sup>.</p><p>Autopsy of patients who have evidence of Alzheimer disease have found CAA in the vast majority of cases (90%). This rate is still high (20-40%) in non-demented elderly individuals <sup>14</sup>. </p><p>Importantly it is usually not<strong> </strong>associated with systemic <a href="/articles/amyloidosis">amyloidosis</a>.</p><h5>Inherited CAA</h5><p>Inherited cerebral amyloid angiopathy is rare, and encountered as an autosomal dominant condition <sup>14</sup>. It mainly differs from spontaneous forms in earlier age of onset, typically in middle to late middle age <sup>14</sup>.</p><h4>Clinical presentation</h4><p>Symptomatic clinical presentation is usually with an <a href="/articles/intracerebral-haemorrhage">intracerebral haemorrhage</a>, found in 40% of autopsy proven cases of CAA <sup>1</sup>. This is often in the form of <a href="/articles/cerebral-microhaemorrhage">microhaemorrhages</a> or of <a href="/articles/lobar-haemorrhage">lobar haemorrhages</a>. Of all patients with cerebral haemorrhage, CAA is found in 4-10% of cases <sup>2</sup>. Vessel damage can also result in ischaemic leukoencephalopathy <sup>1</sup>.</p><p>Uncommonly an inflammatory reaction may be incited and patients can present in a more subacute fashion with declining cognitive performance, seizures, headache and stroke like episodes (without haemorrhage) <sup>11</sup>. This known as <a href="/articles/cerebral-amyloid-angiopathy-related-inflammation">cerebral amyloid angiopathy-related inflammation</a> and is discussed separately. </p><p>Occasionally mass like lesions, known as <a href="/articles/cerebral-amyloidoma">cerebral amyloidoma</a>, have been reported <sup>3,14</sup> (not to be confused with <a href="/articles/cerebral-amyloidosis">cerebral amyloidosis</a> seen in patients with systemic amyloidosis). </p><p>The <a href="/articles/boston-criteria">Boston criteria</a> <sup>7 </sup>is a combination of clinical, radiographic and pathological criteria which are used to assess the probability of CAA.</p><h4>Pathology</h4><p>CAA is characterised by the deposition of ß-amyloid (Aß-40) in the media and adventitia of small and medium sized arteries of the cerebral cortex and leptomeninges <sup>4</sup>. This is associated with fibrinoid degeneration, and microaneurysm formation <sup>1</sup>. Amyloid is an eosinophilic, insoluble protein, located in the extra-cellular space, and stains with Congo red yielding apple green birefringence when viewed with polarized light <sup>3</sup>. It is important to note that amyloid deposition is also encountered in other clinical scenarios including <a href="/articles/spongiform-encephalitis">spongiform encephalitis</a> <sup>1</sup>.</p><h5>Associations</h5><ul><li>
Image 6 MRI (SWI) ( create )
Image 20 MRI (Gradient Echo) ( update )
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