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Childhood chemotherapy may decrease cognitive function in young adults
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Young adults who underwent chemotherapy for leukemia or lymphoma as children showed decreased cognitive flexibility and weaker short-term memory, according to a small Belgium study published in Journal of the National Cancer Institute.
Researchers linked the decreases to levels of a specific protein in brain fluid — phosphorylated Tau. Ability to concentrate and long-term memory appeared unaffected by chemotherapy.
“Tests that require quick switching between tasks or remembering new information for a short amount of time were clearly more difficult for former cancer patients,” Rudi D’Hooge, PhD, director of laboratory for biological psychology and professor of psychology and educational sciences at University of Leuven, said in a press release. “The developmental stage of the brain at the start of the cancer treatment probably plays a decisive role.”
Acute lymphoblastic leukemia and non-Hodgkin lymphoma account for 30% of childhood cancers. Prophylactic cranial irradiation has been shown to prevent relapse and increase survival, but the possibility of late neurocognitive sequelae remains a concern.
Intrathecal and high-dosed IV injections of methotrexate have replaced cranial irradiation in the treatment of childhood leukemia and lymphoma. To determine the impact of those treatments, researchers compared intellectual performance, memory and executive functioning between young adult survivors of ALL (n = 27) and non-Hodgkin lymphoma (n = 4) with age-matched controls (n = 35).
The mean age of all participants was 21.5 years (range, 16.1-29.8 years), and the mean age at diagnosis was 6.4 years. Treatment occurred between 1994 and 2004.
Researchers evaluated neurocognitive performance in relation to intrathecal methotrexate delivered and cerebrospinal fluid levels of Tau — a marker of axonal damage — and phosphorylated Tau (p-Tau), a marker of neurofibrillary tangles.
Adult childhood leukemia and lymphoma survivors displayed statistically significant lower total (P = .001), verbal (P = .02), and performance (P = .007) IQs than controls, although results remained within the range of normality.
Researchers reported a negative correlation between cerebrospinal p-Tau levels and total (r = –0.491; P = .02), verbal (r = –0.629; P = .001) and performance (r =–0.414; P = .04) IQ, but not for cerebrospinal Tau levels (total, r = –0.207; verbal, –0.242; performance, –0.332).
Only performance IQ negatively correlated with total intrathecal methotrexate dose (r = –0.484, P = .007).
“Our team collected samples of brain fluid during the cancer treatment and analyzed the p-Tau levels to measure the damage to the brain cells,” D’Hooge said. “We found that high concentrations of p-Tau predict cognitive problems at a later age.”
Neuropsychological assessments indicated that long-term memory, focused and sustained attention and inhibition — all developed largely before the age of 6 years — remained intact in leukemia and lymphoma survivors. Conversely, cognitive flexibility and information processing, which were affected in various tests, predominantly mature during adolescence. The data suggest that increased levels of cerebrospinal p-Tau is an independent predictor of intellectual functioning in adult survivors of childhood cancer and that multidimensional neurotoxicity assessments should use p-Tau levels as a biomarker.
Researchers noted the small sample size and lack of pretreatment neurocognitive data as limitations of the study.
“If we systematically measure these p-Tau levels in the future, we can offer specific help to children with high values,” Iris Elens, MD, a research assistant in child and youth psychiatry at the University of Leuven, said in the press release. “With early coaching aimed at the most relevant functions we can prevent problems that otherwise manifest 10 to 15 years after the treatment.” – by Chuck Gormley
Disclosures: Olivia Hendrickx Research Fund funded this study. The researchers report no relevant financial disclosures.
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