Cerebral Amyloid Angiopathy (CAA)

What happens in CAA

Beta-amyloid, the same protein that forms plaques in Alzheimer's disease, is deposited in the walls of arteries on the surface and in the outer layers (cortex) of the brain. The vessel walls lose smooth muscle and elasticity, and become brittle and prone to leaking or rupturing. This leads to:

• Lobar intracerebral hemorrhage: bleeding in the outer lobes of the brain rather than deep areas (deep bleeds are more typical of high blood pressure).
• Cerebral microbleeds: tiny old bleeds visible only on special MRI scans.
• Cortical superficial siderosis: iron deposits from bleeding on the brain surface.
• Small strokes and white matter damage from narrowed vessels.

Symptoms

Many people have no symptoms until a bleed occurs.

• Brain hemorrhage: sudden headache, weakness, numbness, speech or vision problems, confusion, seizures or reduced consciousness. See intracerebral hemorrhage.
• Transient focal neurological episodes ("amyloid spells"): brief, repeated episodes of tingling, numbness or weakness that spread over minutes, often mistaken for a TIA or migraine aura. They are often caused by small bleeds on the brain surface and signal a high risk of a larger bleed.
• Cognitive decline: memory and thinking problems, sometimes progressing to dementia.
• Seizures.
• CAA-related inflammation: an uncommon immune reaction causing headache, confusion, seizures and behavior change over days to weeks; it responds to steroids.

Causes and risk factors

• Age: the strongest risk factor; CAA is found in a substantial share of older adults at autopsy.
• Alzheimer's disease: most people with Alzheimer's have some CAA.
• APOE ε4 and ε2 gene variants.
• Inherited forms: rare familial types (for example Dutch-type) cause CAA and bleeds in middle age.
• Down syndrome: due to the extra copy of the amyloid precursor protein gene.
• Prior neurosurgery or cadaveric dura grafts in childhood: linked to early-onset CAA in some reports.

High blood pressure does not cause CAA but increases the risk of bleeding from it.

Diagnosis

CAA can only be proven by examining brain tissue, so doctors diagnose "probable" or "possible" CAA from MRI using the Boston criteria (version 2.0):

• age 50 or older
• lobar hemorrhages, microbleeds or cortical superficial siderosis in typical locations on susceptibility-weighted (SWI) or gradient-echo MRI
• certain white matter features
• no other explanation for the bleeding

CT scan is used first in emergencies to detect bleeding. Lumbar puncture or amyloid PET may help in research or uncertain cases.

Treatment and management

There is no treatment that removes amyloid from vessel walls. Care focuses on preventing bleeds and managing complications.

• Blood pressure control: the most important step; lowering blood pressure reduces the risk of recurrent bleeding.
• Blood thinners: anticoagulants and antiplatelets increase bleeding risk. Decisions are individualized; for people with atrial fibrillation and CAA, a left atrial appendage closure device may be considered instead of long-term anticoagulation.
• Avoid unnecessary NSAIDs and limit alcohol.
• Treat seizures with anti-seizure medicine.
• Acute hemorrhage: emergency stroke care, blood pressure lowering, reversal of blood thinners, and sometimes surgery.
• CAA-related inflammation: steroids or other immune-suppressing drugs.
• Cognitive support and rehabilitation after a bleed.

Alzheimer's antibody treatments

New anti-amyloid antibody drugs for Alzheimer's (such as lecanemab and donanemab) can cause brain swelling and bleeding called amyloid-related imaging abnormalities (ARIA). People with significant CAA features on MRI, such as many microbleeds or superficial siderosis, are at higher risk and are usually not eligible.

Outlook

The outlook varies. Some people have microbleeds and remain stable for years. After a lobar hemorrhage from CAA, the risk of another bleed is considerably higher than after a bleed from high blood pressure, and each bleed can add disability. Cognitive decline is common over time. Blood pressure control and careful medicine choices improve outcomes.

Frequently asked questions

What is cerebral amyloid angiopathy?

CAA is a condition in which beta-amyloid protein builds up in the walls of brain blood vessels, making them fragile. It can cause bleeding in the brain, tiny microbleeds, brief neurological spells and memory decline, mostly in people over 60.

What is the life expectancy with cerebral amyloid angiopathy?

It varies widely. People with only microbleeds may live many years without major problems. After a CAA-related brain hemorrhage, the risk of further bleeds and disability is higher, which affects life expectancy. Blood pressure control and avoiding unnecessary blood thinners help.

Is CAA the same as Alzheimer's disease?

No, but they are related. Both involve beta-amyloid. In Alzheimer's, amyloid forms plaques in brain tissue; in CAA, it deposits in blood vessel walls. Most people with Alzheimer's have some CAA, but CAA can occur without Alzheimer's.

Can people with CAA take blood thinners?

Sometimes, but the decision needs specialist input. Blood thinners raise the risk of brain bleeding in CAA, especially after a prior hemorrhage or with many microbleeds. For atrial fibrillation, alternatives such as left atrial appendage closure may be considered.

What are amyloid spells?

Amyloid spells, or transient focal neurological episodes, are brief, repeated episodes of tingling, numbness or weakness that spread over minutes. In CAA they are often caused by small bleeds on the brain surface. They can look like a TIA but signal a high risk of a larger bleed, so blood thinners may be avoided.