CADASIL and Dementia: Brain Effects and Progression

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease that affects blood vessels, causing recurrent strokes during adulthood.

The symptoms and effects correlate with stroke-induced brain damage and can include dizziness, weakness on one side of the body, and vision changes. Over time, the cumulative impact of strokes in different regions of the brain can lead to dementia and disability.

You or your loved one may need assistance with daily living due to the impact of CADASIL strokes. Treatment can help prevent strokes and manage symptoms. Genetic testing can help in family planning.

Hereditary CADASIL: Causes and Genetic Risk Factors

A specific alteration in the NOTCH3 gene leads to CADASIL.

This condition is inherited in an autosomal dominant pattern. This means that anyone who inherits even one copy of the altered gene will develop the disease. The gene also is not on the X or Y chromosome. Each child of a parent who has CADASIL has a 50% chance of inheriting the altered gene and having CADASIL.

The inherited alteration in the NOTCH3 gene causes changes in the smooth muscle inside small blood vessels, narrowing blood vessels throughout the body. This can block blood flow, and the risk of blockage is highest in the blood vessels of the brain, leading to strokes.

A stroke is a type of brain damage that occurs when a specific region of the brain is briefly deprived of oxygen and nutrients. 

CADASIL Symptom Progression

The first effects of CADASIL generally begin during adulthood. According to the National Institute of Neurological Disorders and Stroke (NINDS), symptoms typically begin between age 20 and 40.

The symptoms of CADASIL correlate to the region in the brain that’s damaged by a stroke. Symptoms can develop suddenly when a stroke occurs, and recurrent strokes in different regions of the brain lead to an accumulation of effects.

Symptoms of CADASIL strokes can include:

• Difficulty walking
• Dizziness
• Headaches
• Paresthesias (unusual sensations) or decreased sensation of one side of the face or body
• Vision changes, such as double vision or loss of vision in one hemisphere (inability to see out of one side of both eyes)
• Weakness of one side of the face or body

A stroke may cause sudden symptoms that improve slightly over time. Fluid and swelling often surround the area of a stroke, and when the fluid and swelling resolve over the next few days or weeks, the symptoms can partially improve.

Dementia Link

Vascular dementia is one of the long-term consequences of living with CADASIL. Dementia is a decline in cognitive abilities (problem-solving, memory, reasoning, and self-care). Dementia has many causes, such as Alzheimer's disease.

In vascular dementia, multiple strokes throughout the brain interfere with cognitive abilities. Thinking, memory, and problem-solving require coordination between areas throughout the brain. The accumulation of many strokes causes a decline in communication between different regions of the brain, eventually leading to vascular dementia.

Symptoms of vascular dementia may include:

• Decreased ability to learn new skills
• Decreased appetite
• Forgetting new information
• Forgetting older information and skills
• Frequent confusion and forgetfulness
• Inappropriate laughing or crying
• Increased sleeping
• Loss of interest in usual activities
• Misplacing items
• Neglecting personal hygiene
• No longer being able to use objects or perform tasks that you used to do
• Not recognizing people or places that you used to know
• Personality changes, such as apprehension and fear

While CADASIL often leads to neurologic decline, a 2022 study of 129 people over 65 found that 17.8% were neurologically intact, showing no decline.

Age of Diagnosis and Symptom Onset

The age of CADASIL diagnosis can vary, depending on the family history. If you know that you or your child is at risk of developing the effects of CADASIL, you may get a diagnosis through genetic testing even before symptoms begin to emerge.

If you haven’t had any family history of CADASIL, the diagnosis may take a while. If you are diagnosed with a stroke at a young age, your healthcare team would consider a range of different stroke risk factors to help identify why you may have had a stroke.

Because CADASIL is uncommon (estimated to affect 2 to 5 out of every 100,000 people), other health conditions that increase the risk of stroke would likely be considered first before you would have genetic testing for CADASIL. 

Effects and Complications After Stroke

After a stroke, you can experience persistent neurological effects and other health complications.

Complications after CADASIL strokes can involve:

• Changes in thinking, memory, concentration, and problem-solving
• Depression 
• Hallucinations (sensing things that aren't there)
• Movement disorders, such as Parkinson's disease 
• Muscle stiffness
• Seizures

Living with decreased mobility can also lead to complications, such as pneumonia (lung infection), urinary tract infections (UTIs), and pressure sores. 

Treatment for Symptom Management 

The treatments for CADASIL are directed to stroke prevention and management stroke effects.

In general, the strokes caused by CADASIL are not usually associated with the typical stroke risk factors—heart disease, hypertension (high blood pressure), diabetes, and high cholesterol. Screening for these risk factors is important for preventing their additive stroke risk. 

Antiplatelet therapy, such as aspirin, which is commonly used to prevent stroke among people who have known risk factors, can sometimes be beneficial for people who have CADASIL. You would have to discuss the risks and benefits with your specialist.

If you’ve already experienced the effects of CADASIL, you may need to have therapy to help optimize your abilities. This may include physical therapy for weakness and coordination difficulties, cognitive therapy for signs of dementia, and psychotherapy or medication for mood disorders.

Life Expectancy Statistics

Studies have estimated a life expectancy of 65 years for men and 71 years for women with CADASIL.

It can be hard to predict how long a person will survive after diagnosis of CADASIL. The recurrent strokes associated with this condition are not usually fatal, but any stroke can be fatal if it affects a crucial part of the brain or causes a substantial injury, such as a fall.

Different variants of CADASIL also affect the risk of stroke and the age of the first stroke. But even people with the same gene variation can have different courses of the disease.

In one study of 41 people with CADASIL, 54% were still alive after 18 years in the study. Deaths occurred at ages ranging from 50 to 75. Those who were older, more disabled, had strokes, and had lacunes (small cavities) seen in brain imaging were more likely to have died.

Coping, Support, and Resources

Living with a chronic disease that doesn’t have a cure can be challenging and stressful. You don’t have to cope all by yourself. Seek support from professionals or from others who are living with the same condition. 

A few resources you may consider:

• Alzheimer's Society
• cureCADASIL
  
• Hunter's Hope
  
• National Organization for Rare Disorders (NORD)
  

Enrolling in a Clinical Trial 

While some treatments can help improve your outcome of living with CADASIL, there is no cure currently. You may consider learning about clinical trials so that you can have access to emerging treatment options.

You can find information about clinical trials through your doctor, who may be able to help you identify which trials would be a good fit for you. Additionally, you can look for information through the CADASIL support groups and through the NINDS.

Summary

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disorder that causes blood vessel disease and strokes. The main effects of this condition occur due to brain damage from small strokes throughout the brain and may involve cognitive deficits (trouble with memory and reasoning), as well as weakness, dizziness, personality changes, and headaches.

Stroke prevention is a key component of managing this disease, and rehabilitation after stroke can improve quality of life. If you have a family history of CADASIL, it’s important to maintain close medical care so you can have the most effective treatment available to you.