Doxorubicin chemotherapy-induced "chemo-brain": Meta-analysis

Area of Science:

• Neuroscience
• Oncology
• Pharmacology

Background:

• Doxorubicin is a widely used chemotherapy agent that halts cancer cell replication.
• Chemotherapy, including doxorubicin, can cause cognitive impairment, often termed "chemo-brain."
• The mechanism of doxorubicin-induced neurotoxicity is debated due to its inability to cross the blood-brain barrier, suggesting indirect pathways.

Purpose of the Study:

• To conduct the first meta-analysis on the cognitive performance of patients treated with doxorubicin.
• To quantify the impact of doxorubicin on various cognitive domains.
• To identify specific cognitive functions affected by doxorubicin treatment.

Main Methods:

• A systematic literature search of PubMed and MedLine was performed, identifying 494 studies.
• 14 studies meeting specific criteria were included in the meta-analysis.
• Cognitive performance of 511 doxorubicin-treated women with breast cancer was compared to 306 healthy controls.

Main Results:

• Doxorubicin-treated patients showed significant global cognitive impairment (g = -0.41, P < 0.001).
• Specific impairments were observed in executive function (g = -0.25), language (g = -0.30), memory (g = -0.12), and processing speed (g = -0.28).
• Short-term verbal memory was particularly affected (g = -0.21), while attention, motor function, and visuospatial abilities remained intact.

Conclusions:

• Doxorubicin treatment is associated with prevalent cognitive deficits in multiple domains, supporting the concept of doxorubicin-mediated chemo-brain.
• Cognitive functions such as attention and motor skills appear unaffected, suggesting domain-specific neurotoxicity.
• Findings can inform the development of interventions to improve quality of life and refine doxorubicin therapies to minimize off-target damage to healthy tissues.