Photo courtesy of Columbia University
Neuropsychology exam
A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.
Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.
They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”
The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.
All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.
"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."
Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.
Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor. Parental socioeconomic status was a covariate.
Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.
Findings
Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.
They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.
Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).
And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.
Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).
However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).
The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.
For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.
But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.
Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.
Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.
"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."
The Olivia Hendrickx Research Fund supported the study.
