Sandbox: Post-chemotherapy cognitive impairment
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, minimental state examination)