Effects of chemotherapy and organophospates on the brain

PhD students
Myrle Stouten-Kemperman
Sanne Menning


Michiel de Ruiter (Chemotherapy)
T + 31 (0)20-5129006
E. m.b.deruiter@amc.uva.nl
Liesbeth Reneman (organophosphates)
T +31 (0)20-5668312
E. L.Reneman@amc.uva.nl

Key Publications
Hum Brain Mapp 2012
Hum Brain Mapp 2011
Brain Imaging and Behavior 2014 (in press)

Cancer patients that have been treated with cytotoxic agents often complain of memory and concentration problems in 15-50% of cancer survivors, even years after cessation of chemotherapy. The department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute – Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL Dr. S. Schagen and Dr. M.B. de Ruiter), focuses on cognitive dysfunction in cancer patients and survivors. Up till now, the mechanisms underlying these cognitive deficits are poorly understood and have not been studied well. In a close collaboration with the NKI-AVL research, since 2006, we investigate neural substrates of cognitive dysfunction in cancer patients with state-of-the-art imaging techniques at the MRI facility at the AMC.

We found that 10 years after high-dose adjuvant chemotherapy, breast cancer survivors have long-term cognitive impairments on fMRI tasks and neuropsychological testing. MRI studies in this same group of patients revealed several potential neuroimaging markers for this late cognitive decline, which include assessments of white matter integrity, as well as gray matter integrity. We are currently investigating neuroimaging markers for cognitive impairment in breast cancer patients prospectively, and in addition study the effects of chemotherapy in testicular cancer survivors.

In a pilot study we investigated the effects of another neurotoxic agent organophosphates (OPs) on the human brain. Cabine air in airplanes can be contaminated with engine oil contaminants. These contaminations may contain OPs which are known neurotoxins to brain white matter. We investigated whether we could objectify cognitive complaints in aircrew and whether we could find a neurobiological substrate for their complaints. In twelve aircrew members we found significantly more self-reported cognitive complaints and depressive symptoms, and a higher number of tests scored in the impaired range compared to eleven well matched controls (car racers). We observed small clusters in the brain in which white matter microstructure was affected. Also, we observed higher cerebral perfusion values in the left occipital cortex, and reduced brain activation on a functional MRI executive function task. The extent of cognitive impairment was strongly associated with white matter integrity, but extent of estimated number of flight hours was not associated with cognitive impairment nor with reductions in white matter microstructure. Defects in brain white matter microstructure and cerebral perfusion are potential neurobiological substrates for cognitive impairments and mood deficits reported in aircrew.