Post-chemotherapy cognitive impairment

Post-chemotherapy cognitive impairment (also known as chemotherapy-induced cognitive dysfunction) is defined as the cognitive impairment that can result from chemotherapy treatment. Post-chemotherapy cognitive impairment was first discovered and described in 1980. Post-chemotherapy cognitive impairment is characterized by changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy. Approximately 20-30% of patients that undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The exact pathogenesis of post-chemotherapy cognitive impairment is not fully understood. However, the underlying mechanisms of the disease are believed to be caused by direct neurotoxicity. Genes involved the development of post-chemotherapy cognitive impairment, include COMT nucleotide polymorphism, Apolipoprotein E gene, and BDNF gene mutations. Post-chemotherapy cognitive impairment is more commonly observed among middle aged and elderly patients. The median age at diagnosis ranges between 40-70 years old. There are no specific imaging findings associated with post-chemotherapy cognitive impairment. However, in some cases MRI may detect accurate measurement of therapy-induced changes in grey and white matter volumes. Recent studies suggest further investigation on the underlying mechanisms of cognitive impairment.

Post-chemotherapy cognitive impairment was first discovered and described in 1980 following the increasing number of breast cancer survivors.^[1]

There is no classification system for post-chemotherapy cognitive impairment.^[1]

• The pathogenesis of post-chemotherapy cognitive impairment is not fully understood.^[1]
• However, the underlying pathophysiology is believed to be caused by direct neurotoxicity.
• Genes involved the development of post-chemotherapy cognitive impairment, include:^[2][3]

• COMT nucleotide polymorphism
• Apolipoprotein E
• Brain-derived neurotropic factor (BDNF) gene

• Common chemotherapeutic agents causing post-chemotherapy cognitive impairment, include:^[4]

• Cyclophosphamide
• 5-fluorouracil
• Methotrexate

• Post-chemotherapy cognitive impairment must be differentiated from other diseases that cause cognitive impairment (such as, lack of attention, orientation to time and space), such as:^[1]

• Dehydration
• Infection
• Sepsis

• The prevalence of post-chemotherapy cognitive impairment remains unknown but approximately 20-30% of patients that undergo chemotherapy experience some level of post-chemotherapy cognitive impairment.^[5]

• Post-chemotherapy cognitive impairment is more commonly observed among patients aged 40-70 years old.

• Females are slightly more commonly affected with post-chemotherapy cognitive impairment than males.

• There is no racial predilection for post-chemotherapy cognitive impairment.

The most common risk factor in the development of post-chemotherapy cognitive impairment include:

• High number of cycles of chemotherapy.^[4]
• Smoking^[3]

There is insufficient evidence to recommend routine screening for Post-chemotherapy cognitive impairment.

• The majority of patients with post-chemotherapy cognitive impairment are initially asymptomatic.^[1]
• Early clinical features, include:

• Lack of attention
• Memory loss
• Problems to recall
• Lack of orientation

• If left untreated, patients with post-chemotherapy cognitive impairment may progress to develop severe cognitive impairment.
• Common complications of post-chemotherapy cognitive impairment, include:^[4]

• Decreased executive function
• Cerebrovascular disorders
• Focal neurological deficits

• Prognosis is generally good, and symptoms of post-chemotherapy cognitive impairment typically disappear in about four years.

There are no established criteria for the diagnosis of post-chemotherapy cognitive impairment. The diagnosis of post-chemotherapy cognitive impairment is based on the history and symptoms.

• Patients with post-chemotherapy cognitive impairment may have aggravating factors such as:

• Anxiety
• Depression

• Post-chemotherapy cognitive impairment is usually asymptomatic at diagnosis.
• Symptoms of post-chemotherapy cognitive impairment may include the following:^[1]

• Memory loss
• Lack of attention
• Difficult language fluency
• Poor calculation and recall
• Loss of appetite
• Irritability or constant mood swings
• Hopelessness

• Patients with post-chemotherapy cognitive impairment usually appear malnourished and pale.
• Physical examination shows no remarkable findings for patients with post-chemotherapy cognitive impairment.^[4]

• There are no specific laboratory findings associated with post-chemotherapy cognitive impairment.^[1][6]
• In some cases, elevated levels of apolipoprotein (APOE) allele may be seen in patients with post-chemotherapy cognitive impairment

There are no ECG findings associated with post-chemotherapy cognitive impairment.

There are no x-ray findings associated with post-chemotherapy cognitive impairment.

There are no echocardiography/ultrasound findings associated with post-chemotherapy cognitive impairment.

There are no CT scan findings associated with post-chemotherapy cognitive impairment.

There are no MRI findings associated with post-chemotherapy cognitive impairment.

There are no other imaging findings associated with post-chemotherapy cognitive impairment.

There are no other diagnostic studies associated with post-chemotherapy cognitive impairment.

• The majority of cases of post-chemotherapy cognitive impairment are self-limited and require only supportive care including:
  • Behavioral interventions
    • Relaxation
    • Exercise
    • Group therapy
    • Brain-training programs
  • Pharmacologic interventions
    • Modafinil
    • Methylphenidate
    • Donepezil

Surgery is not recommended for patients with post-chemotherapy cognitive impairment.

There are no primary preventive measures available for post-chemotherapy cognitive impairment.

There are no secondary prevention measures available for post-chemotherapy cognitive impairment.