Why, after Chemotherapy, is it Necessary to Assess Memory Using Translational Testing?

Abstract

As the number of cancer survivors rises, so does the importance of understanding what happens post-chemotherapy. The evidence is clear that chemotherapy affects not only cancer cells, but also healthy cells including neurons, leading to long-term cognitive dysfunction in a large portion of survivors. In order to understand the mechanism of action and in the hope of reducing the potential neurocognitive side effects of chemotherapy, pre-clinical testing should be used more effectively. However, the field is lacking translation from clinical studies to animal models. Spatial learning and memory paradigms based on the water maze, the most commonly used rodent model, are available for translational testing in humans and could overcome this weakness. There is an overwhelming need in the field to understand whether the water maze is an adequate model for post-chemotherapy impairments or whether other paradigms should be used. This is of great importance for the understanding of the mechanisms, side effects of new drugs, appropriate pharmacotherapy, and confounding factors related to chemotherapy treatment regiments. This review is very important to both basic scientists and clinicians determining how translational paradigms are critical to future cancer research, as well as what type of paradigms are appropriate in our technically advancing society.

What you do not know Could Hurt You: What Women Wish their Doctors Had Told them about Chemotherapy Side Effects on Memory and Response to Alcohol

“…9,12 The majority of the US participants report a diminished memory regardless of time postchemotherapy and a reduced way-finding particularly in those with greater than one year postchemotherapy, which is consistent with previous studies. 11,13,39,40 Although fewer PR women report short-term memory loss and way-finding, .20% reported a decline in both. This study was limited in what type of memory loss patients were asked to report; consequently, a difference in reporting of a specific type of memory loss may not represent an actual difference in memory loss overall.…”

“…This is consistent with numerous reports of long-term spatial learning and memory impairments reported postchemotherapy. 13 Fewer PR women (34.8%) compared to US women (54.5%) reported that a medical professional discussed the cognitive side effects of chemotherapy with them ( Table 5). The majority (PR 73.9% and US 78.8%) of participants wished that they had received information about how chemotherapy and other medications can affect memory (Table 5), which did not significantly correlate with whether an individual reported an impairment (data not shown).…”

“…[9][10][11][12] Specifically, long-term neurological side effects have been seen with methotrexate and 5-flourouracil, the most common chemotherapy drugs used to treat gynecological cancers. 9,12,13 Even a single intravenous injection of methotrexate resulted in a sustained reduction in hippocampal cell proliferation. 14 Another study suggests that the size of gray and white matters in the parahippocampal gyrus and prefrontal regions was reduced following a year-long course of chemotherapy treatment.…”

“…13,22 Indeed, cognitive therapy protocols exist that reduce the acute effects of chemotherapy treatment on verbal memory, attention, and processing speed when initiated immediately after patients are stabilized. 12,13,[16][17][18][19] However, patients cannot request a preventative or postchemotherapy treatment if that they do not know whether it exists or that it might be necessary that underscores the essential importance of educating patients about the possibility of memory loss due to chemotherapy. 13 Though alcohol intake differs among cultures and gender, the relation between alcohol intake and higher risk of breast cancer appears to be universal.…”

“…12,13,[16][17][18][19] However, patients cannot request a preventative or postchemotherapy treatment if that they do not know whether it exists or that it might be necessary that underscores the essential importance of educating patients about the possibility of memory loss due to chemotherapy. 13 Though alcohol intake differs among cultures and gender, the relation between alcohol intake and higher risk of breast cancer appears to be universal. In a 2007 publication, the World Cancer Research Fund and the American Institute for Cancer Research reported that the association between an increased risk of breast cancer and an increased alcohol intake is one of the steadiest findings among the many hypothesized relationships between dietary factors and risk for breast cancer.…”