What is Cerebral Amyloid Angiopathy (CAA)?

CAA is defined by a type of protein deposit in the wall of blood vessels in the brain. CAA is actually a common process in aging and usually harmless. In some people with severe CAA, however, the protein deposits cause the blood vessel walls to crack, in which case blood can leak out and damage the brain. The damage from this process is called a bleeding (or hemorrhagic) stroke.

Figure 1
Figure 1

This figure shows a microscopic view of a section of a brain with CAA. The round structures are blood vessels cut in cross section. The walls of the vessels contain amyloid, which stains pink with greenish streaks when illuminated by the technique used in this figure.

The protein deposits in CAA are made of a material called amyloid that is very similar to deposits found in the brain in Alzheimer's disease (AD). Despite this close relationship and an increased tendency for the two diseases to occur together, most patients with AD do not have CAA, and most with CAA do not have AD.

What are the symptoms of CAA?

The blood that leaks out of a vessel damaged by CAA can cause the surrounding region of the brain to suddenly stop working properly, resulting in symptoms like weakness or paralysis of the limbs, difficulty speaking, loss of sensation or balance, or even coma. If blood leaks out to the sensitive tissue around the brain, it can cause a sudden and severe headache. Other symptoms sometimes caused by irritation of the surrounding brain are seizures (convulsions) or short spells of temporary neurologic symptoms such as tingling or weakness in the limbs or face.

Figure 2
Figure 2

This is a section of the brain at autopsy in a patient who died after a CAA-related bleeding stroke. The dark area in the lower right has been destroyed by leakage of blood into the brain.

I've heard about amyloid affecting parts of the body outside of the brain. Is that the same disease as CAA?

No. Confusion arises because the term amyloid describes several different proteins which are not necessarily related to each other. The amyloid that causes CAA does not affect organs outside of the brain and spinal cord, while the amyloid deposits that damage the kidneys, heart, or other organs in the body very rarely have any impact on the brain.

What are the risk factors that cause some people to get CAA?

To a considerable extent this remains a mystery. No food or environmental exposure has been shown to cause CAA; neither have various other conditions that affect blood vessels such as high blood pressure or diabetes. The only definite risks for CAA are advancing age (it's occasionally diagnosed in people in their 50's or 60's but is much more common in people in their 70's and 80's), the accompanying presence of AD, and some types of genes. In particular, a gene called apolipoprotein E appears to be a risk factor for CAA, but is not useful for predicting who will or won't get the disease. Most people with this gene do not develop CAA and many with the disease do not have the risky gene.

Is CAA the only cause of bleeding stroke?

No. There are other diseases that can cause blood vessels in the brain to break open, such as longstanding high blood pressure or weak areas (aneurysms) in blood vessel walls. CAA is responsible for approximately 30-40% of bleeding strokes in the elderly.

Is there a test doctors perform to diagnose CAA?

There is no test to diagnose CAA with 100% certainty during a patient's lifetime, but there are several ways to know if this disorder is a strong possibility in a patient with a bleeding stroke. Imaging tests like CT scans or MRI scans can show whether the bleeding occurred in the outer part of the brain (the cortex) where CAA is usually most severe. This can help distinguish CAA from bleeding strokes caused by high blood pressure, which tend to occur in deep sections of the brain. In addition, a kind of MRI scan called gradient-echo MRI can show whether there have been other tiny areas of bleeding that are also in the typical locations for CAA.

Figure 3
Figure 3

This is a CT scan of a patient with a bleeding stroke caused by CAA. The two bright areas represent recent areas of bleeding into the brain. Both areas are in the outer part of the brain that is characteristic for CAA-related strokes.

Some patients with large bleeding strokes require surgical removal of a blood clot from their brain. The removed tissue can be examined with a microscope to determine whether the amyloid protein is present in the blood vessels.

What happens after a patient has a CAA-related bleeding stroke?

The survival and recovery from bleeding strokes in CAA depends on a number of factors including the amount of bleeding, the location in the brain where it occurs, and the age and health of the patient. While some patients die from bleeding strokes, others can eventually make excellent recoveries with little or no loss of strength or other skills. Treatments that are sometimes used during the weeks or months after a bleeding stroke include anti-seizure and anti depression medicines.

Are patients who recover from a CAA-related stroke at risk for future bleeding strokes?

Unfortunately yes. The rate of a second bleeding stroke in CAA is approximately 10% per year, which means that some patients will go many years after their first stroke without any trouble, while others may have a second stroke within a few months to a few years of the first.

Figure 3
Figure 4

These are MRI scans using a particularly sensitive technique for bleeding strokes. They are from the same patient, taken several years apart. The image on the right shows the development of a new bleeding stroke (appears black, marked by arrow).

Are there steps CAA patients can take to help prevent a stroke from recurring?

Most patients with CAA should avoid agents that "thin the blood" or interfere with blood clotting. The medicine with the strongest effect on blood clotting (and thus the riskiest for CAA patients) is warfarin (also known by its trade name "Coumadin"). Other medicines that have weaker effects on the blood are aspirin, aggrenox, clopidogrel ("Plavix"), and most of the anti-inflammatory medications such as ibuprofen. Patients who have had bleeding strokes should discuss these medications carefully with their doctor before using them, as they may carry more risk than benefit. Also, while high blood pressure does not appear to be a major contributor to CAA, it is usually prudent to monitor the blood pressure after a patient recovers from a bleeding stroke and maintain it in the normal range.

Unfortunately there have been no medicines yet shown to lower the risk of recurrent bleeding in CAA. This is a major focus of research in this field.

If my family member has CAA, will I get it too?

Probably not. There are some families (primarily from Denmark, Iceland, and Belgium) that inherit CAA in a dominant fashion, but most CAA patients do not have any affected family members. While other genes such as apolipoprotein E (see above) may slightly affect the risk for CAA, their association with the disease appears to be too weak to cause multiple cases to cluster in a family.

What are doctors and scientists learning about CAA?

CAA is not a "new" disease, but it's only in the past few years that neurologists and other physicians have appreciated its important role in causing bleeding strokes in the elderly. It is now possible for a stroke specialist to diagnose CAA with some degree of certainty.

Ongoing research in CAA has several goals, including:
  • To develop improved diagnostic techniques for detecting CAA
  • To predict which patients with CAA are at risk for stroke recurrences after they recover from their first stroke
  • To identify treatments that can substantially lower the risk for stroke recurrence in CAA.

How can CAA patients participate in research?

Patients who might be interested in participating in projects to identify diagnostic techniques and risk factors for CAA can contact us. There are currently no experimental trials to identify drugs for CAA currently underway, but there are several promising avenues that may lead to drug trials over the next few years. We encourage patients or family members who would like more information about our current and future research studies to contact us.