Cure Cerebral Amyloid Angiopathy

This page is meant to be a resource for our patients and anyone living with CAA or caring for someone with CAA.  CAA is a terrible disease that causes memory and cognitive loss and intracerebral hemorrhage.  Curing CAA would be a victory, not only for our patients, but also in the fight against Alzheimer's disease and dementia.
What is cerebral amyloid angiopathy?

How is it diagnosed?

How is it treated?

Is it genetic?
What is CAA-related inflammation?

Why is CAA important in the search for a treatment for Alzheimer's disease?


CAA is a disorder of the small blood vessels of the brain.  A small, abnormal protein called β-amyloid accumulates in the brain during aging.  In Alzheimer's disease, this protein clumps together a forms toxic plaques in the brain; in CAA the same protein is deposited on small arteries.  Once there, it unleashes a number of toxic effects -- including activating the immune system to attack the blood vessels.  This causes the blood vessels to become fragile and prone to breaking.  It also makes it more difficult for the brain to regulate blood flow.

The combined effects of these problems often leads to slowing of processing speed on neuropsychiatric testing and patients and their families often report memory problems.  These fragile blood vessels can often also lead to intracerebral hemorrhages. 

This process usually progresses slowly and most patients with CAA are over age 60 (although there are rare exceptions). 
What is cerebral amyloid angiopathy (CAA)
The most useful test for diagnosing CAA is an MRI of the brain, particularly the susceptibility weighted sequence.  This scan essentially puts blood products under a magnifying glass, enabling us to see microhemorrhages in the brain which are often 1mm or less in diameter.  These show up on the scans as black dots and appear 2-3x larger on the scans than they actually are.  In CAA, these microhemorrhages occur in a distinctive pattern -- they are in the cortical grey matter or at the junction of the grey and white matter, but do not involve the deeper structures of the brain (the basal ganglia, pons or cerebellum).  When we see this pattern in an older adult, it is strongly suggestive of CAA.

Neuropsychiatric testing can also help to make a diagnosis of CAA.  Patients often have similar symptoms as those with Alzheimer's disease, but with the addition of prominent slowing of processing speed.  While neuropsychiatric testing cannot make the diagnosis of CAA on its own, it is a helpful test.

There are a few other tests which we do not obtain very often in the clinic unless a case is confusing.  These include PET scans (FDG-PET, which shows us areas of the brain which are not as active as they shoud be), "Amyloid PET" (including the original beta-amyloid PET probe PiB; these show us how much beta-amyloid is in the brain and where it is) and cerebrospinal fluid testing of β-amyloid and tau levels.  In a few cases, we also consider genetic testing.
How is CAA diagnosed?
We do not have a treatment for CAA yet that specifically stops or slows β-amyloid deposition in the blood vessels.  Treatment for each patient should be taylored to their particular needs and considers the other medical problems they have, so these are just general principles.

We primarily focus on three things to reduce the frequency of hemorrhages and protect memory:

1) We try to achieve tight blood pressure control.  This is the only treatment for CAA that has been shown in a randomized controlled trial to reduce the frequency of hemorrhage.  It is helpful for patients to check their blood pressure at home regularly and bring these measurements to their doctors.

2) Avoid blood thinners.  We generally try to keep people off of drugs like coumadin/Warfarin, Eliquis, Xarelto, Pradaxa, etc.  We also prefer patients to not take aspirin, plavix or other mild blood thinners that act on the platelets unless they absolutely need to.  These decisions need to be made individually for each patient.

3) Avoid head trauma.  To do this, we generally focus on lowering the risk of falls and avoiding a few trauma-prone activities and hobbies. 

The rest of our treatments work to improve symptoms.  We sometimes use memory enhancing drugs like those used in Alzheimer's disease and we aggressively treat anxiety, depression and sleep disorders because this seems to make a big difference for our patients.
How is CAA treated?
Usually not, most CAA is sporadic rather than inherited.  There are a few families who have mutations which lead to CAA, but this is rare and generally causes a form of CAA which is severe and starts a decade or more earlier than typical CAA.

There are some genes that influence the risk of developing CAA, the most famous of which is ApoE4.  These genes are important scientifically because they help us understand the disease better, but they do not change an individual person's risk enough that we need to check them clinically. 
Is CAA genetic?