Cancer-Related Cognitive Impairment or Old Age?

Cancer-related cognitive impairment affects many survivors of the disease, but researchers are still not quite sure if it is the disease itself or other factors that contribute to this decline.

AnnaLynn Williams, PhD, conducted research as a graduate student at the University of Rochester analyzing cognitive decline in patients with chronic lymphocytic leukemia (CLL) — who may already be at risk due to their old age. Williams, who is now a postdoctoral research fellow at St. Jude Children’s Research Hospital, sat down with Oncology Nursing News^® to discuss her findings.

Can you discuss the issue of cancer-related cognitive impairment?

Cancer-related cognitive impairment is a really significant issue for our cancer patients. We estimate that it affects anywhere from 30 to 70% of patients, both during and after treatment. Patients often experience problems with memory or paying attention, being able to focus, and really completing daily tasks.

We know that if they have issues with cognitive impairment, it affects their quality of life, it might affect their ability to read or drive, their ability to connect socially, and most importantly their ability to return to work or school if they are younger patients.

What was the rationale to use CLL as a model to study differential roles of disease and treatment in cancer-related cognitive impairment?

It's becoming more and more apparent to use that cancer-related cognitive impairment is a real phenomenon that affects many of our patients. Now we need to understand who, exactly, is at risk, and when they are at risk. Is it only during and after treatment, or is it possible that they're actually at risk for impairments even before we treat them?

We do have some evidence from breast cancer studies that suggests a subgroup of patients is actually experiencing cognitive problems before we treat them with chemotherapy. Given that piece of information, we became really interested in this question of, 'Is the cancer itself contributing to the cognitive impairment?' This led us to think of chronic lymphocytic leukemia.

We also knew that to-date, no research had really been done in elderly hematologic malignancy populations, and CLL is a cancer that affects older patients, with a median age of 72. It naturally follows that those patients may actually be at risk for cognitive impairment just due to normal aging. So, we felt that it was really important to use that population to, first of all, characterize their risk of cognitive impairment, but also to try to give us the idea of what the cancer, itself, is contributing. CLL is a very unique tumor. It's very slow-growing, indolent, and many patients don't actually need treatment for years after their diagnosis.

This provides us with a natural treatment-free comparison group for us to look at disease effects as well as treatment effects.

What was the goal, methods, and results of the research?

The goal of our study was really to try to tease apart disease and treatment effects. We wanted to know how much the tumor itself contributing to the patients' cognitive impairment. In addition, we wanted to actually characterize cognitive impairment in this population because no one had done so yet.

What we did was recruit 150 CLL patients, 50 of whom had been treated with chemotherapy before, and 100 had never had chemotherapy treatment before but had the disease for some time. In those untreated patients, we further classified them into high-risk and low-risk patients, meaning they had a higher risk of disease progression or needing treatment sooner, or lower risk. We brought them in and they did a whole neuropsychological battery.

What we found was that between 10% and 30% of CLL patients were impaired in tests of memory and executive function. What we also found was that treated patients performed not that differently from untreated patients on our objective measures of cognitive function but treated patients self-reported significant impairment compared to our untreated patients, indicating to us that the small differences are actually really meaningful to our patients.

What we found most interesting was that the patients with higher-risk disease performed worse, both significantly and clinically meaningfully function, compared to patients with low-risk disease. This was regardless of if they had chemotherapy in the past. This signals to us that what we hypothesized was true. The disease itself is likely involved in cognitive impairment in these patients.

I will say that this is the first study looking at this, and we do need to replicate these findings in a larger, longitudinal study. We don't fully understand why this might be happening, but I think it's important that if patients are feeling these symptoms or have these concerns that they raise them with their oncology team because they likely have resources that they can provide to them to help cope with these symptoms and possibly mitigate them altogether.

It's important for our oncology community to recognize that cognitive impairment really spans the entire cancer experience and that it's important to monitor patients early on, even from diagnosis, especially our elderly patients as they progress from diagnosis through treatment and into survivorship.