Chronic inflammation linked to cognitive difficulties among older breast cancer survivors
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Higher levels of the inflammatory marker C-reactive protein predicted lower reported cognitive function among older breast cancer survivors, according to study results published in Journal of Clinical Oncology.
The findings add to evidence that links chronic inflammation with cognitive problems among cancer survivors, researchers wrote.
Background
Most breast cancer survivors in the U.S. are aged 60 years or older, and as many as half of survivors have cognitive problems following treatment, according to Judith E. Carroll, PhD, associate professor of psychiatry and biobehavioral sciences and faculty member of Cousins Center for Psychoneuroimmunology at UCLA.
“Our patients and advocacy research partners told us that cognitive problems were one of the most concerning symptoms they were living with as survivors,” Carroll told Healio. “We also knew from a lot of research in cancer-related cognitive decline, including our own work, that cognitive problems might be related to inflammation. By testing this idea, we hope that we can develop ways to reduce inflammation and reduce cognitive problems.”
The Thinking and Living with Cancer (TLC) study enrolled women aged 60 years or older with newly diagnosed, stage zero to stage III primary breast cancer and no dementia, neurologic disorders or other cancer from September 2010 to March 2020. Researchers frequency-matched noncancer controls to survivors based on age, education level and race (white vs. nonwhite).
Study participants underwent assessments annually for up to 60 months.
During each visit, investigators evaluated cognition with the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and neuropsychologic testing. They acquired at least one blood sample for C-reactive protein (CRP) assays from 400 survivors (median age, 67.8 years; 82.8% white) and 329 noncancer controls (median age, 67.6 years; 83.6% white). Most survivors (60.9%) had stage I disease, and 87.6% had ER-positive tumors.
Researchers analyzed survivor-control differences in natural log-transformed C-reactive protein (ln-CRP) through mixed linear effect models and used random effect-lagged fluctuation models to gauge ln-CRP directional effects on subsequent cognition.
Key findings
Researchers observed significantly higher mean ln-CRP among survivors compared with controls at baseline and 1-year, 2-year and 5-year visits (P < .05 for all).
Moreover, higher adjusted ln-CRP levels appeared predictive of lower reported cognitive function among survivors but not controls (P = .008 for interaction), regardless of depression or anxiety.
Compared with controls, survivors had 9.5-point lower adjusted FACT-Cog scores at CRP levels of 3 mg/L and 14.2-point lower scores at CRP levels of 10 mg/L.
Survivors also performed worse on neuropsychological tests than controls, but the tests did not show a link between CRP and cognition.
“We were surprised to not see associations of inflammation measured by CRP and neuropsychological tests, but we know that these tests are not as good at detecting subtle problems as survey items that are based on what survivors tell us,” Carroll said.
Implications, next steps
Clinicians need to understand factors that could alter a woman's risk for cognitive difficulties after breast cancer treatment and to monitor their symptoms, especially if they have high CRP inflammation levels, Carroll told Healio.
“CRP is routinely included in blood panels as it’s a risk factor for cardiovascular disease,” Carroll said. “Checking for elevations in CRP among older survivors is good clinical practice for long-term health. Lowering inflammation may help with cognitive function, although we did not directly test this, so we will need more research to provide specific directives for clinical practice.”
It is also important to consider the specific reasons for elevated CRP and whether behavioral or pharmacologic interventions could reduce inflammation, Carroll said.
“There have been a few studies now showing reductions in inflammation by lowering stress, improving physical activity and sleep. These might be important behaviors we could target to improve long-term cognitive function, as well,” she said. “Similarly, we should test whether treatment of inflammation with pharmacologic methods could also provide some benefit.”
References:
- Carroll JE, et al. J Clin Oncol. 2022;doi:10.1200/JCO.22.00406.
- Long-term study supports link between inflammation and cognitive problems in older breast cancer survivors (press release). Published Sept. 30, 2022. Accessed Sept. 30, 2022.
For more information:
Judith E. Carroll, PhD, can be reached at jcarroll@mednet.ucla.edu.
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