Cognitive Late Effects

Some treatments for childhood cancer increase risk for long-term problems in cognitive function. These problems are known as cognitive late effects. These problems may become noticeable months or even years after treatment, and may change over time.

Children treated for brain tumors or acute lymphoblastic leukemia (ALL) are more likely to be affected due to the therapies used to treat these cancers. However, cognitive problems have been identified in survivors of other cancers as well.

Cognitive impairments can have significant impact on quality of life. Children with cognitive late effects are more likely to have problems in school and have lower academic achievement. They are also more likely to have trouble with employment, independent living, and development of social relations.

Understanding potential risks to cognitive function can help families plan regular evaluations to watch for problems, develop a plan for addressing issues that arise, and better support patients as they navigate life decisions.

Risk factors for cognitive late effects

Risk factors for cognitive late effects include:

• Radiation to head, neck, or upper spine or total body radiation therapy (TBI), particularly at a young age
• Certain chemotherapy medicines, especially high dose intravenous (IV) methotrexate, cytarabine, and/or intrathecal treatments
• Brain surgery and related factors including extent of surgery and brain regions affected
• Use of corticosteroid medications

Other factors that increase risk include younger age at treatment, the intensity (dose and duration) of treatment, and medical complications such as stroke, hydrocephalus, infection, or seizures. Females who are treated with cranial radiation are at higher risk for cognitive late effects compared to males. Survivors who develop chronic health conditions including heart, lung, or endocrine disease are also at higher risk for cognitive problems.

Brain changes due to treatments

Cognitive impairments related to cancer treatments are thought to begin with change in the white matter of the brain. White matter is made up of myelin, which provides a sort of insulation to nerve fibers and allows signals to travel quickly between neurons. Myelination and the development of white matter continues through young adulthood.

Over time, differences in grey matter of the brain are also seen. Grey matter is made up of neurons, or nerve cells, which are responsible for information processing and communication in the brain.

Maturation in brain white matter and grey matter corresponds to increases in cognitive function including attention, reasoning, and problem solving.

Certain chemotherapy treatments and cranial radiation can interfere with white matter development in the frontal lobe of the brain. This can cause cognitive impairments that become more noticeable over time. Treatment may also impact grey matter in certain brain regions such as the hippocampus, a structure involved in memory formation that is particularly sensitive to cranial radiation.

Treatments may also damage the brain by causing inflammation and damage to cells and blood vessels. Damage to blood vessels in the brain can lead to a range of effects including bleeding and strokes. The strokes may be large with sudden noticeable changes, or small with subtle changes that accumulate over time. These effects may occur months to years after treatment.

Other treatment-related factors can impact cognitive function indirectly. These include problems in hearing and/or vision, missed school, and emotional or social issues.

Assessment of cognitive function

The medical specialty that focuses on learning, behavior, and brain development is called neuropsychology. A neuropsychological assessment measures different aspects of function including:

• Achievement skills such as reading and math
• Attention and concentration
• Learning and memory
• Organization, planning, and problem solving
• Language
• Visual-spatial skills
• Motor coordination
• Behavioral, emotional, and social function

Measures of global intelligence and academic achievement are also important to cognitive assessment. Observations from parents and teachers are also used to evaluate a child’s strengths and weaknesses in cognitive processes, emotions, social skills, and behavior.

Onset of cognitive problems

Cognitive difficulties related to childhood cancer and its treatment may result in:

• A loss of function compared to previous abilities or
• Lower function compared to what would be considered normal for age and development.

For most childhood cancer survivors, cognitive problems are not due to a loss of skills. Problems are more often caused by a slower rate of learning. Children still learn and develop new skills, just not as fast as their peers do.

Cognitive late effects in childhood cancer survivors are often related to problems in executive function. This includes working memory, flexible thinking, and self-control. These skills enable a person to plan, organize, and problem solve. Deficits are often seen in attention, processing speed, and the ability to organize and complete tasks.

Problems may become more noticeable during key times of academic transitions. As children mature, parents and teachers expect greater independence in organization and applied learning. For children with cognitive impairments, the increasing demands become harder to manage. Skills and abilities do not keep pace with expectations, and peers progress at a faster rate.

Cognitive impairments often impact educational and career potential. These difficulties can also have a negative effect on social and emotional functioning as well as overall quality of life.

Early intervention and ongoing monitoring can help survivors manage cognitive late effects.

Ways to manage cognitive late effects

Cancer treatments often cause some damage to brain structures that may or may not be permanent and that may cause a range of effects, from very mild to severe. Understanding individual limitations is important to provide appropriate interventions and resources to meet patient needs. Healthy lifestyle changes can also help improve and protect cognitive health.

Making healthy food choices, reducing stress, and managing health conditions such as obesity, diabetes, and heart disease are also important for brain health and cognitive function. Heart disease and lung problems that can occur as late effects of cancer treatments can contribute to impaired cognitive function. Therefore, a lifelong approach to health – including brain health – is important for all cancer survivors.