Cancer Therapy's Impact on Cognitive Function May Be Due to Accelerated Aging

Cancer-related cognitive impairment—sometimes called “chemo brain”—is a pervasive phenomenon that can negatively impact patients’ quality of life and lead to depression, anxiety, and fatigue. Studies of the cognitive performance of patients with breast cancer before and after chemotherapy have demonstrated that patients experience significant declines in cognitive function scores following treatment.

Building on the knowledge that certain cancer treatments, such as radiation and many chemotherapy agents, work by damaging the DNA of cancer cells while collateral damage to the DNA of normal, healthy cells, a study published this week in Cancer, the journal of the American Cancer Society, suggests that some treatments speed up the biological aging process. According to the study’s findings, this aging effect could be linked to the cognitive decline experienced by patients undergoing cancer treatment.

The research team, led by Judith E. Carroll, PhD, associate professor of psychiatry at the University of California Los Angeles Cousins Center for Psychoneuroimmunology and the Semel Institute for Neuroscience and Human Behavior, assessed a cross-sectional sample of 94 women who had undergone treatment for early breast cancer.

The women ranged in age from 36 to 69 years, and had been treated between 3 and 6 years prior to inclusion in the study. The patients were evaluated for indicators of biological aging, including elevated levels of DNA damage, reduced telomerase enzymatic activity, shorter telomere length in blood cells, and levels of the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII). Cognitive function was assessed using a neuropsychological test batter and a self-report, and linear regression models examined the relationships between biological aging and cognitive outcomes.

The researchers found that the patients who had higher levels of DNA damage and who had lower telomerase activity also had lower executive function scores after adjusting for factors such as age, body mass index, race, number of years from treatment, and intelligence scores (standardized coefficients [B], —0.23 and 0.30; P <.05).

Furthermore, lower telomerase activity was linked with worse attention and reduced motor speed scores (B values, 0.30 and 0.24; P <.05). Telomere length and sTNF-RII levels, however, were not correlated with any neurocognitive domains.

Carroll and colleagues concluded that these findings point to a significant association between biological markers of aging and objective measures of cognitive performance. Future prospective studies will be needed, however, to confirm whether anticancer therapy has a causal role in biological aging that drives cognitive function decline.

“These findings are important because they provide further information about what might be happening after cancer treatment that impacts cognitive decline in some individuals. This information can inform future research and may lead to new interventions to prevent these cognitive declines,” said Carroll. “The work is novel by identifying key factors in biological aging and connecting them to cognitive function, which initiates new avenues of research.”

Reference

Carroll JE, Van Dyk K, Bower JE, et al. Cognitive performance in survivors of breast cancer and markers of biological aging [published online November 26, 2018]. Cancer. doi: 10.1002/cncr.31777.