Cerebral Amyloid Angiopathy

CAA, Amyloidosis – cerebral, Congophilic angiopathy

Cerebral amyloid angiopathy is a condition where abnormal proteins build up in the blood vessels of the brain, making them fragile and prone to bleeding. While many people may have this condition without knowing it, it can lead to serious problems like strokes and gradual loss of thinking abilities, especially in people over age 60.

Table of contents

• What is cerebral amyloid angiopathy?
• Symptoms and how the condition develops
• Causes and risk factors
• How the condition is diagnosed
• Treatment and management
• Outlook and complications

What is cerebral amyloid angiopathy?

Cerebral amyloid angiopathy is a condition that causes bleeding inside your brain that damages brain tissue. It happens when amyloid (abnormal) proteins build up in the blood vessels of your brain and make your blood vessels leaky. These protein deposits are typically found in the walls of small to medium-sized blood vessels in the brain, as well as in the outer protective layers called the leptomeninges.^[1][3]

The protein buildup weakens the walls of blood vessels, making them fragile and prone to breaking. This leads to bleeding in your brain that can be small, called microbleeds, or larger brain bleeds known as intracranial hemorrhage. The bleeding typically occurs in the outer parts of the brain, called the cortex, rather than in the deeper areas.^[1][2]

Cerebral amyloid angiopathy is the most common cause of cognitive decline, which is when you gradually lose your thinking abilities. The condition is also one of the leading causes of intracerebral hemorrhage (bleeding inside the brain) in older adults.^[1][5]

The condition is quite common in older people. Experts estimate that 23% to 29% of people in the general population above the age of 50 have moderate to severe cerebral amyloid angiopathy. The percentage increases significantly with age, with some estimates suggesting prevalence as high as 50% by age 90.^[1]

Symptoms and how the condition develops

Symptoms vary depending on how much blood is leaking into your brain. Many people could have cerebral amyloid angiopathy without having symptoms. This can happen if you only have silent microbleeds, when very little blood is seeping into your brain. In some cases, people learn they have cerebral amyloid angiopathy after having a brain imaging test for another issue.^[1]

The way this condition develops is similar to a very slow leak. There are clumps of amyloid proteins that cling to the inside wall of blood vessels in your brain. Over many years, your blood vessel walls gradually weaken and develop microscopic cracks or fissures that let blood seep into your brain. When blood leaks from ruptured vessels, it damages brain tissue. If you’re like most people, you won’t notice changes like memory loss or confusion at first. And when you do, you may think those symptoms are a natural consequence of growing older.^[1]

Some people have gradual memory problems. When imaging scans are done, there are often signs that they have had bleeding in the brain that they may not have realized.^[2]

More severe bleeding causes noticeable symptoms that may resemble a stroke. These include:^[1][2]

• Headache, usually in a certain part of the head
• Confusion or episodes of confusion
• Difficulty talking or speech problems
• Sudden weakness or paralysis
• Cognitive impairment or loss of mental function
• Seizures (also called amyloid spells)
• Double vision or decreased vision
• Sensation changes
• Drowsiness
• Vomiting
• In severe cases, stupor or coma

Symptoms get worse over time as amyloid proteins do more damage to your blood vessel walls and larger amounts of blood flow into your brain.^[1]

When the condition develops quickly

The condition can develop quickly, but this usually happens only if you inherit certain genetic mutations (changes) that cause the condition. For example, the most common type of inherited cerebral amyloid angiopathy causes life-threatening strokes. These serious strokes are the first symptom. People who survive a stroke often have dementia, epilepsy, and recurring strokes that do further damage to their brains. Most people with this type of cerebral amyloid angiopathy die within 10 years of developing symptoms. Inherited cerebral angiopathy is very rare.^[1]

Causes and risk factors

The exact cause of cerebral amyloid angiopathy is not fully understood. In most cases, the factors that result in amyloid protein deposition in older patients are not well understood.^[3]

Research suggests the following conditions or situations may increase your risk:^[1]

• Increasing age: The major risk factor is age. The condition is more often seen in people older than 55 or 60 to 65 years old. It is uncommon before age 60 and even rarer for those in their 50s.^[2][3]
• Alzheimer’s disease: There appears to be a connection between the two conditions
• Race: People who are white are more likely to have the condition than people in other ethnic groups
• Hypertension (high blood pressure): There is a possible association, though this is disputed between experts

Some evidence has demonstrated a relationship with apolipoprotein E (APOE). Researchers found that patients with APOE epsilon 2 or epsilon 4 alleles seem to be at a greater risk for cranial hemorrhages than the general population.^[3]

Inherited forms

The condition can sometimes be passed down through families, but this is rare. Cases of “presenile” cerebral amyloid angiopathy are caused by mutations in the amyloid precursor protein (APP) gene. Examples of other mutations resulting in familial cerebral amyloid angiopathy include ACys peptide, ATTR peptide, PrPSc peptide, ABri peptide, ADan peptide, and AGel peptide.^[2][3]

How the condition is diagnosed

There is no conclusive way to diagnose this condition while a person is alive. The only way to do that with certainty is to examine samples of a person’s brain under a microscope. This is usually done after death or when a biopsy of the blood vessels of the brain is done.^[1][2]

However, healthcare providers can strongly suspect the condition based on symptoms, physical examination, and imaging tests. A physical exam can be normal if the bleed is small. There may be some brain function changes. It is important for your healthcare provider to ask detailed questions about the symptoms and medical history.^[2]

Imaging tests

Imaging tests of the head that may be done include:^[2]

• CT scan or MRI scan to check for bleeding in the brain. The MRI scan, particularly the susceptibility weighted sequence, is especially useful as it can show microbleeds in the brain that are often 1mm or less in diameter
• MRA scan to check for large bleeds and rule out other causes of bleeding
• PET scan to check for amyloid deposits in the brain

The diagnosis is often based on seeing a distinctive pattern of bleeding on brain imaging. In cerebral amyloid angiopathy, microhemorrhages occur in a specific pattern—they are in the outer grey matter or at the junction of the grey and white matter, but do not involve the deeper structures of the brain like the basal ganglia, pons, or cerebellum.^[3]

Treatment and management

There is no known effective treatment that can cure cerebral amyloid angiopathy or stop the buildup of amyloid proteins. The goal of treatment is to reduce risk by modifying risk factors and to relieve symptoms.^[2]

Blood pressure control

Achieving tight blood pressure control is one of the most important treatments. This is the only treatment that has been shown in a randomized controlled trial to reduce the frequency of hemorrhage. Patients are encouraged to check their blood pressure at home regularly and bring these measurements to their doctors. The goal is typically to keep systolic pressure (the top number) under 120.^[1]

Avoiding blood thinners

Patients are generally advised to avoid drugs that thin the blood or make bleeding more likely. These include anticoagulants like coumadin/Warfarin, Eliquis, Xarelto, and Pradaxa. Healthcare providers 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. The awareness of a diagnosis is important in clinical practice as it impacts decisions to use lifelong anticoagulation.^[5]

Symptom management

In some cases, rehabilitation is needed for weakness or clumsiness. This can include physical, occupational, or speech therapy. Sometimes, medicines that help improve memory, such as those for Alzheimer disease, are used. Seizures may be treated with anti-seizure medicines.^[2]

Healthcare providers also aggressively treat anxiety, depression, and sleep disorders because this seems to make a big difference for patients.^[2]

Preventing falls

Avoiding head trauma is important. Healthcare providers generally focus on lowering the risk of falls and avoiding trauma-prone activities and hobbies.^[2]

Inflammatory form

In a minority of patients, the presence of cerebral amyloid angiopathy triggers an autoimmune inflammatory reaction, referred to as CAA-related inflammation (CAA-RI). This form is often responsive to immunosuppressive treatment in the acute phase.^[5]

Outlook and complications

The disorder slowly gets worse over time.^[2]

The severity of cerebral amyloid angiopathy can vary widely, and the condition may be asymptomatic in some people. As a result, it can be challenging to predict outcomes. Factors that can influence the prognosis include the severity of the condition, the presence of any underlying medical conditions, the individual’s overall health and lifestyle, and how that person responds to treatment.^[3]

Prognosis is dependent on how the condition presents, with worse outcomes in patients with large hematomas and older age. Some people with cerebral amyloid angiopathy may have a good prognosis and be able to live a normal life span with proper treatment. However, for others, it can be a serious and potentially life-threatening condition. The risk of death is higher in individuals with multiple strokes or severe cognitive impairment.^[3]

Possible complications

Complications may include:^[2]

• Dementia
• Seizures
• Repeated episodes of bleeding in the brain
• Hydrocephalus (rarely)

When to seek emergency care

Go to the emergency room or call 911 or the local emergency number if you have sudden loss of movement, sensation, vision, or speech.^[2]