What is Cerebral Amyloid Angiopathy?
Cerebral amyloid angiopathy (CAA) is a kind of brain blood vessel disorder. What distinguishes it is the build-up of a protein known as amyloid beta-peptide that lodges within the brain’s blood vessels. This buildup causes the blood vessels to become fragile, leading to possible brain bleeding in certain parts of the brain.
Aside from causing brain bleeds, CAA could also lead to memory problems, small unnoticed bleeding, iron accumulation in the brain, a disease condition causing swelling, brain damage, Alzheimer’s disease, or passing neurological symptoms. It may appear in some hereditary conditions or happen without a specific cause.
To diagnose CAA, we usually combine clinical symptoms, pathological signs, and imaging results. However, the most accurate way to confirm CAA is through an examination of the brain after death. Unfortunately, at this time, there are no treatments that can modify the course of the disease.
The prognosis, or the likely outcome of CAA varies. It can be determined by the symptoms a patient presents. Nevertheless, outcomes can be worse for older-age patients and those with large blood clots in the brain.
What Causes Cerebral Amyloid Angiopathy?
The exact cause of cerebral amyloid angiopathy isn’t fully clear. This condition happens when a protein called amyloid-beta accumulates in the brain covering (leptomeninges) and certain brain blood vessels. As a result, these blood vessels lose strength and can easily bleed. This can happen either in certain families due to genetic syndromes, or it can appear randomly.
Genetic cerebral amyloid angiopathy (CAA)
Some types of early-onset CAA are caused by changes in a gene called the amyloid precursor protein (APP). Other examples of genetic changes that cause CAA include alterations in ACys, ATTR, PrPSc, ABri, ADan, and AGel peptides or proteins.
Randomly occurring CAA
In older adults, the factors causing the buildup of the amyloid-beta protein are not fully understood. Research suggests that certain types of a protein known as apolipoprotein E (APOE) might be involved. It seems that people with certain variants of this APOE protein (epsilon 2 or epsilon 4 alleles) might be more likely to experience brain bleeds than the average person.
Risk Factors and Frequency for Cerebral Amyloid Angiopathy
Cerebral amyloid angiopathy, or CAA, is a condition that is closely linked to age. The occurrence of moderate to severe CAA tends to increase as we grow older. It’s unusual to see this condition in people under 60 or 65, and it’s even less common in people in their 50s. CAA doesn’t seem to favor one gender over the other. Some experts think there’s a link between CAA and high blood pressure, but not all agree on this.
- Cerebral amyloid angiopathy (CAA) is more likely to occur as you age.
- Moderate to severe CAA increases with age.
- It’s rare for people under 60 or 65 to get it, and even rarer for those in their 50s.
- CAA affects both males and females equally.
- Some experts believe there could be a connection between CAA and high blood pressure, but this is not unanimously agreed upon.
Signs and Symptoms of Cerebral Amyloid Angiopathy
Cerebral amyloid angiopathy is a condition that often doesn’t show any symptoms. But when it does, it usually leads to spontaneous bleeding in the brain. The location and size of the bleeding can have different effects. Large bleeds towards the brain’s ventricles can lead to hemiplegia (paralysis of one side of the body) and decreased awareness. Smaller bleeds could lead to localized deficits, headaches, or seizures. At times, very small bleeds may not cause any symptoms at all. The bleeds often happen more in the back of the brain and are typically found in the cerebellar cortex and vermis, part of the cerebellum, due to the build-up of a certain protein called amyloid-beta peptide.
Cognitive impairment, such as difficulties with memory or thinking, can also be a symptom of this condition. Three patterns have been observed:
- Gradual decline – due to tiny bleeds, small cavities of lost tissue in the brain, microscopic areas of tissue death due to inadequate blood supply, and damage to the brain’s white matter due to lack of blood flow.
- Step-wise decline – due to repeated bleeds in brain
- Rapidly progressive decline – due to inflammation related to cerebral amyloid angiopathy
Testing for Cerebral Amyloid Angiopathy
The Boston criteria are a set of guidelines often used to assess the likelihood of Cerebral Amyloid Angiopathy (CAA), a condition linked to the brain. These criteria take into account a person’s clinical information, brain imaging results, and any pathologies. While a conclusive diagnosis can only be made by examining the brain after death, the Boston criteria help in forming a ‘probable’ diagnosis during a person’s lifetime by using brain imaging or tissue sampling.
The Boston Criteria are divided into four parts:
1. Definite CAA (postmortem) – This can only be confirmed after death when a postmortem examination of the brain shows signs of specific types of brain damage, with no other cause, and severe CAA with vasculopathy.
2. Probable CAA (with pathology) – This requires clinical evidence and physical tissue that shows specific types of hemorrhage, traces of CAA, and no other diagnostic lesions.
3. Probable CAA (with imaging) – This is identified when clinical records and brain images show multiple or single hemorrhages in specific regions, no other diagnostic damage, and the patient’s age is 55 or above.
4. Possible CAA (with imaging) – Base on the patient’s clinical evidence and imaging indicating a single brain hemorrhage in specific areas, or widespread superficial siderosis, no other diagnosable lesions, and the patient is 55 years or older.
For imaging evaluations, Gradient-echo magnetic resonance imaging (MRI) is typically used. This MRI technique shows areas of iron accumulated from old hemorrhages, which help to determine the diagnosis of CAA. Along with this, another method known as susceptibility-weighted MRI is also used, which is more sensitive than the previous technique.
Pathology samples from brain biopsies are rarely used in diagnosing CAA, reserved only when CAA-related inflammation is suspected. If viable, the sample should be tested with the beta-amyloid immunostain or Congo red stain to detect the deposition of amyloid beta-peptide, a key factor in confirming the diagnosis of CAA.
Treatment Options for Cerebral Amyloid Angiopathy
Management of Intracerebral Hemorrhage (ICH) connected with Cerebral Amyloid Angiopathy (CAA) is generally based on the symptoms a patient exhibits. Immediate care for patients with these conditions involves procedures similar to any spontaneous ICH. Focusing on controlling blood pressure and managing intracranial pressure is critically important. If surgery is required, the risk of death generally remains the same compared to other forms of ICH. Both presence of blood in the brain’s ventricles and the age of patients (75 years or older) affect the outcome adversely.
ICH linked with CAA often happens again. Due to this high chance of recurrence, doctors typically avoid prescribing antiplatelet and anticoagulant drugs unless there is a compelling reason for their use. Interestingly, some research has shown benefits in restarting anticoagulation therapy in patients with an irregular heartbeat condition known as atrial fibrillation.
Despite CAA not being prominently linked with hypertension, controlling blood pressure has been linked with reducing the risk of death. The PROGRESS trial showed a significant 77% reduction in the risk of CAA-related ICH when blood pressure was properly managed. Moreover, other observations have supported these findings, suggesting that maintaining lower blood pressure can reduce the risk of another ICH.
Lastly, there’s some limited evidence that shows benefits from using immunosuppression (drugs that lower the body’s immune response) to treat inflammatory forms of CAA. Small studies have shown that using certain drugs like cyclophosphamide or glucocorticoids resulted in sustained clinical improvement. Other immunosuppressive drugs such as mofetil, mycophenolate, and methotrexate have also been associated with benefits.
What else can Cerebral Amyloid Angiopathy be?
Nontraumatic ICH, or internal bleeding in the brain, can occur due to several reasons:
- Bleeding from a brain tumor
- Bleeding following a stroke caused by a blocked blood vessel
- Bleeding that spreads from a smaller area in the brain affected by high blood pressure
- Arteriovenous malformation (an abnormal connection between arteries and veins in the brain)
Imaging tests might also identify other conditions that could look similar to nontraumatic ICH, such as:
- High blood pressure leading to small blood vessel disease in the brain
- Bleeding from cancer that has spread to the brain
- Multiple cavernoma syndrome (a condition characterised by multiple abnormal blood vessels in the brain and spinal cord)
- Diffuse axonal injury (a type of traumatic brain injury)
- Damage to brain blood vessels caused by radiation treatment
- Neurocysticercosis (a parasitic infection of the brain)
What to expect with Cerebral Amyloid Angiopathy
The outlook for cerebral amyloid angiopathy varies greatly based on where the intracerebral hemorrhage (ICH) is located and its size. Typically, larger hemorrhages and older age (75 and over) lead to less favorable outcomes. On the other hand, ICHs that don’t affect the ventricles or are located closer to the surface of the brain often lead to better results. Mortality rates range from 10% to 30%, but patients with higher consciousness levels and smaller hemorrhages (less than 50 mL) tend to have the best prognosis. It’s important to note that cerebral amyloid angiopathy runs a high risk of recurrent hemorrhage compared to hemorrhage caused by high blood pressure. Research has shown recurrence rates to be around 21%.
Cerebral amyloid angiopathy is often linked with temporary and long-term neurological problems. Temporary issues might include short, recurring episodes of numbness, tingling, and weakness. While we don’t fully understand why these occur, luckily, they usually don’t last long. Long-term issues can result in slower cognitive speed and a reduction in memory recall. Interestingly, Alzheimer’s disease and cerebral amyloid angiopathy are often found together. There’s also a proven correlation between cerebral amyloid angiopathy and vascular dementia – a common type of dementia caused by reduced blood flow to the brain.
Possible Complications When Diagnosed with Cerebral Amyloid Angiopathy
Besides stroke-like symptoms, Cerebral amyloid angiopathy (ICH) can cause several other problems such as:
- Short-lived neurological symptoms
- Small areas of bleeding in the brain
- Deposits of blood breakdown products in the surface layers of the brain
- Inflammation related to CAA
- Problems with thinking and memory
Preventing Cerebral Amyloid Angiopathy
Cerebral amyloid angiopathy (CAA) is a specific type of brain disorder where a protein known as amyloid builds up in the brain’s small to medium-sized blood vessels and the inner linings of the brain’s membranes. This buildup causes the blood vessels to become fragile, which can lead to bleeding in the brain. Along with this, it can cause a range of problems, including memory and thinking issues, small unnoticed bleeds, iron deposits, white matter brain disease, Alzheimer’s disease, or temporary neurological symptoms.
CAA can either occur on its own or it can be part of certain genetic syndromes. Doctors usually diagnose it by means of clinical evaluations, analyzing tissue samples and making use of imaging techniques like radiography. As of now, there are no treatments available that can stop the progress of this disease. The outcome for patients greatly depends on the specific symptoms they experience with CAA. For instance, patients who experience larger blood clots or who are older usually face more serious health outcomes.
