Post-chemotherapy cognitive impairment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Chemotherapy-induced cognitive dysfunction; Chemo brain; Chemo fog; Chemobrain; PCCI

Overview

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 gray and white matter volumes. Recent studies suggest further investigation on the underlying mechanisms of cognitive impairment.

Historical Perspective

• Post-chemotherapy cognitive impairment was first discovered and described in 1980.

Classification

• There is no classification system for post-chemotherapy cognitive impairment.

Pathophysiology

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

• COMT nucleotide polymorphism
• Apolipoprotein E
• BDNF gene

• On gross pathology, characteristic findings of post-chemotherapy cognitive impairment, include:

• No remarkable findings

• On microscopic histopathological analysis, characteristic findings of post-chemotherapy cognitive impairment, may include:

• Smaller tumor size
• Reduced cellularity
• Extensive cytoplasmic vacuolization causing tumor cells to resemble histiocytes
• Tumor necrosis
• Atrophy and marked nuclear atypia

Causes

• Common causes of post-chemotherapy cognitive impairment, include:

• Cyclophosphamide
• 5-fluorouracil
• Methotrexate

Differentiating Post-Chemotherapy Cognitive Impairment from Other Diseases

• 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:

• Dehydration
• Infection
• Sepsis

Epidemiology and Demographics

• Post-chemotherapy cognitive impairment is rare.
• Approximately 20-30% of patients that undergo chemotherapy experience some level of post-chemotherapy cognitive impairment.
• The prevalence of post-chemotherapy cognitive impairment remains unknown.

Age

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

Gender

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

Race

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

Risk Factors

• The most common risk factor in the development of post-chemotherapy cognitive impairment are number of cycles of chemotherapy.

Natural History, Complications and Prognosis

• The majority of patients with post-chemotherapy cognitive impairment are initially symptomatic.
• 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:

• Decreased executive function
• Cerebrovascular disorders
• Focal neurological deficits

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

Diagnosis

Symptoms

• Post-chemotherapy cognitive impairment is usually symptomatic at diagnosis
• Symptoms of post-chemotherapy cognitive impairment may include the following:

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

• A directed history should be obtained to ascertain:

• Aggravating factors, such as:

• Anxiety
• Depression

Physical Examination

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

Laboratory Findings

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

Imaging Findings

• There are no imaging findings associated with post-chemotherapy cognitive impairment.
• In some cases, MRI may detect accurate measurement of therapy-induced changes in gray and white matter volumes.

Treatment

Medical Therapy

• There is no treatment for post-chemotherapy cognitive impairment; the mainstay of therapy is supportive care.
• Common medical therapies for the treatment of post-chemotherapy cognitive impairment, include:

• Hormonal therapy

Surgery

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

Prevention

• There are no primary preventive measures available for post-chemotherapy cognitive impairment.
• Once diagnosed and successfully treated, patients with post-chemotherapy cognitive impairment are followed-up every visit.
• Follow-up testing includes cognitive function assessments (such as, mini–mental state examination)