A Potential Biomarker Identified

A team led by Alexandre Chan, associate professor in the Department of Pharmacy at the National University of Singapore (NUS) Faculty of Science, recently investigated levels of biomarkers in relation to “chemobrain” to better understand its cause. The team characterized plasma levels of the biomarker dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS) to be biological determinants of cognitive function.

DHEAS is a neurosteroid that helps regulate brain development and function, but whether its levels correlate with cognitive function or are associated with the onset of “chemobrain” were previously unknown.

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For this study, researchers recruited 81 patients with early-stage breast cancer who had no prior exposure to chemotherapy or radiotherapy and were scheduled to receive chemotherapy treatment with curative intent. This was a multicenter, prospective cohort study conducted in the National Cancer Centre Singapore and KK Women’s and Children’s Hospital between 2011 and 2016.

The researchers found that patients with early-stage breast cancer who had a higher plasma DHEAS level prior to chemotherapy had a lower risk of experiencing cognitive decline in the specific domains of verbal fluency and mental acuity.2

Understanding of Cognitive Impairment Still Elusive

Characterizing the presence or severity of cognitive impairment is challenging because no definitive diagnostic criteria have been accepted, explained Dr Beck. It’s also very difficult to understand confounding factors, such as cognitive changes associated with menopause, concomitant brain irradiation, or preexisting cognitive changes such as age-related decline or prior traumatic brain injuries. “Other treatment-related side effects can be additive, such as fatigue, sleep deprivation, anxiety, or pain. So, all of these factors have to be controlled for when assessing prevalence,” she said.

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Most data on cognitive impairment in cancer survivors were obtained from survivors of breast and hematologic cancers. Survivors of other cancers may not be well represented because of this focus.

“Most efforts have focused on treatment of cognitive impairment, not prevention. Examples include medications used for cognitive impairment associated with dementia (eg, donepezil, nemantidine) or CNS stimulants (eg, modafinil, methylphenidate),” said Dr Beck. But nonpharmacologic measures, such as some apps associated with brain training, biofeedback, or relaxation techniques, have been shown to be helpful.


1. Moore K, Stutzman S, Priddy L, Olson D. Chemobrain: a pilot study exploring the severity and onset of chemotherapy-related cognitive impairment. Clin J Oncol Nurs. 2019;23(4):411-416.

2. Toh YL, Shariq Mujtaba J, Bansal S, et al. Prechemotherapy levels of plasma dehydroepiandrosterone and its sulfated form as predictors of cancer‐related cognitive impairment in patients with breast cancer receiving chemotherapy. Pharmacotherapy. 2019;39(5):553-563.