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Chemotherapy-induced peripheral neuropathy tied to compromised executive function



Chemotherapy-induced peripheral neuropathy (CIPN) is linked to a decline in executive and neuromuscular function, a new finding that may increase the risk for compromised mobility and fall risk.

“Among older cancer survivors treated with chemotherapy, the presence of CIPN was independently associated with reduced executive function,” said study investigator Brendan L. McNeish, MD, of the department of physical medicine and rehabilitation, University of Pittsburgh.

“Importantly, given the emerging relationship of executive function with mobility in this population, stakeholders and clinicians are called to acknowledge that chemotherapy-related mobility declines in CIPN survivors are likely due to both neuromuscular and executive dysfunction,” he said.

The findings were presented at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Research gap

Characterized by numbness, tingling, pain, and motor impairment, CIPN affects up to 50% of all patients with cancer that is treated with taxane-, platinum-, or vinca alkaloid–based chemotherapy. The condition is among the leading dose-limiting toxicities, potentially increasing mortality risk.

Though the effects of chemotherapy on cognitive function are well-established, less is known about a potential relationship between this side effect and CIPN, Dr. McNeish said.

“Chemotherapy can be neurotoxic, but few studies have linked neurotoxicity to the central nervous system and peripheral nervous system,” Dr. McNeish said.

To compare cognitive outcomes in patients treated with chemotherapy who did and did not develop CIPN, the investigators conducted a cross-sectional study that included 50 chemotherapy-treated cancer survivors at a single time point post chemotherapy. The mean age of participants was 65.6 years, and 90% were women.

Twenty-two (44%) patients had CIPN on the basis of patient-reported distal paresthesias or numbness that started when chemotherapy was initiated and was present at the time of study enrollment.

Patients with CIPN had a greater decline in executive function, compared with those without the condition, as measured by the Trail Making Test Part B (TMT-B; CIPN-positive, 84.9 sec vs. 59.1 sec, respectively; P = .01) and the Stroop Color and Word Test (SCWT; CIPN-positive, 178.1 sec vs. CIPN-negative, 152.7 sec; P = .04), as well as lower rapid reaction accuracy (CIPN-positive, 60.3% vs. CIPN-negative, 70.6%; P = .01).

The association between CIPN and decreased executive function remained after multivariate adjusting for age, gender, depression, and benzodiazepine use for TMT-B (beta, 18.7; P = .046) and rapid reaction accuracy (beta, -.088; P = .018) but not SCWT (beta, 9.52; P = .233).

Clinical guidance

A recent study by the same investigators showed a link between executive function and balance in cancer survivors (mean age, 65.6 years; 88% women) treated with chemotherapy.

Another study of 116 patients treated with chemotherapy, including 32 who developed CIPN, showed that those with CIPN were nearly three times more likely to report a fall or near fall than were those without CIPN symptoms. In addition, those with CIPN symptoms were also more likely to have received medical care for falls.

Based on the current findings, the research suggests that “current clinical approaches to caring for this growing population [of cancer patients] should not assume that the well-known increased fall risk is solely related to CIPN.”

Dr. McNeish speculated that two potential hypotheses could explain the association between CIPN and reduced executive function in older cancer survivors.

“First, CIPN is associated with other conditions such as depression and anxiety, which are associated with reduced executive function,” he said.

“The second is that cancer-related cognitive dysfunction and CIPN share pathogenic mechanisms of neuronal injury, inflammation, and advanced aging, and thus some patients are vulnerable to both central (cancer-related cognitive function) and peripheral neurotoxicity.”

Either way, Dr. McNeish noted that “all interventions should measure both CIPN and executive function, as one could confound the other.”


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