Use of Chemotherapy and Risk of Alzheimer’s Disease in Colorectal Cancer Survivors

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In a retrospective cohort study reported in JCO Oncology Practice, Akushevich et al found that receipt of chemotherapy was associated with a reduced risk of Alzheimer’s disease in colorectal cancer survivors.

As stated by the investigators, “Evidence on the nature of the relationship between patients receiving chemotherapy as an essential part of guideline-concordant cancer care and the onset of Alzheimer’s disease and other adverse cognitive outcomes has been mixed. Biological mechanisms were proposed to support both a potentially beneficial and an adverse role.”

Study Details

The study involved Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 135,834 patients older than age 65 diagnosed with colorectal cancer between 1998 and 2007.

The effects of chemotherapy vs no chemotherapy were assessed in a proportional hazards model, with individual inverse probability weights being calculated to produce a weighted population pseudo–randomly assigned with regard to all predictors used in the model (propensity score–based method).

Key Findings

After inverse probability weighting, chemotherapy use was associated with decreased risk of Alzheimer’s disease (hazard ratio [HR] = 0.791, P < .0001). The reduction in risk remained significant through 6 years after diagnosis.

For any exposure, use of fluorouracil (HR = 0.860), oxaliplatin (HR = 0.665), irinotecan (HR = 0.629), and cetuximab (HR = 0.326) were associated with significantly reduced risk of Alzheimer’s disease (all P < .0001); reductions associated with use of panitumumab and capecitabine did not achieve statistical significance.  

Chemotherapy use was also associated with reduced risk (all P < .0001) for Alzheimer’s disease–related diseases (HR = 0.823) dementia-permanent mental disorder (HR = 0.807), dementia-senile (HR = 0.772), vascular dementia (HR = 0.804), and cognitive deficits-late effects (HR = 0.885). Chemotherapy was associated with increased risk of cerebral degeneration excluding Alzheimer’s disease (HR = 1.067, P < .0001).

The investigators concluded, “Chemotherapy use in colorectal cancer survivors demonstrated an association with reduced risk for Alzheimer’s disease and other neurocognitive disorders.”

Arseniy P. Yashkin, PhD, of the Biodemography of Aging Research Unit, Duke University, is the corresponding author for the JCO Oncology Practice article.

Disclosure: The study was supported by grants from the National Institutes of Health/National Institute on Aging. For full disclosures of the study authors, visit

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