Effects on the visual system might contribute to some of the cognitive deficits of cancer chemotherapy-induced ‘chemo-fog’

Abstract

SUMMARY The diminution in certain aspects of cognitive function that is reported to occur in some patients during or after adjuvant cancer chemotherapy is variously known as ‘chemo-fog’, ‘chemo-brain’ or other such term. In addition to reported deficits in attention, concentration and other functions, most, if not all, of the studies report deficits involving visual-spatial function or visual memory. Since the visual system is part of the nervous system, it seems reasonable to ask if it is susceptible to some of the deleterious effects produced by adjuvant chemotherapeutic drugs. We propose here the possibility that some portion of the vision-related aspects of the ‘chemo-fog’ spectrum of cognitive deficits results from a direct action of the adjuvant drugs on the visual system or from drug / drug or site / site interaction between effects on the visual system and other critical brain regions.

Engaging neuroscience to advance translational research in brain barrier biology

“…First, modulating these pathways and switches would allow fine-tuning of transporter activity so that transporters can be turned off for controlled periods, thus providing a time window to deliver drugs 58 . Second, such strategies could be used to up-regulate expression and activity of efflux transporters in the NVU in order to minimize brain side effects associated with the treatment of a disease in the periphery (e.g., “chemobrain” in cancer patients) 59 . Third, efflux transporters are affected by — and likely contribute to — disease pathology of CNS disorders that are accompanied by inflammation, oxidative stress and neurotransmitter release, including cancer, epilepsy, and Alzheimer’s disease 60–62 .…”

Structural Brain Differences in Breast Cancer Patients Compared to Matched Controls Prior to Chemotherapy

“…= 0.001 uncorrected, with a cluster-wise correction at p FWE = 0.05 and a set cluster size larger than 10 voxels. ROIs investigated in this study were selected from several sources: the affected regions in previous post-chemotherapy structural and functional studies (Inagaki et al, 2007, McDonald et al, 2010, Abraham et al, 2008, Deprez et al, 2010, Kreukels et al, 2005, Kreukels et al, 2006, Kreukels et al, 2008, Silverman et al, 2007, Saykin et al, 2006, de Ruiter et al, 2010, Raffa & Tallarida, 2010,and related papers considered in light of possible confound variable effects, such as stress and cytokine activity. ROIs extracted included bilateral: frontal lobe, precentralgyrus, cingulate gyrus, parahippocampus, hippocampus, insula, thalamus, basal ganglia, temporal lobe, parietal lobe, precuneus, occipital lobe, brainstem and cerebellum.…”

A proposed mechanism for chemotherapy-related cognitive impairment (‘chemo-fog’)

“…For this reason, the recent proposal by Aluise et al (7) is particularly exciting. Doxorubicin (DOX), one of the more widely used adjuvant agents for the treatment of breast cancer, impairs learning /memory in rodents (8, 9) and DOX-treated patients test lower in cognitive scores and visuospatial skills (10, 11). Although DOX is cytotoxic (it produces its peripheral cytotoxic effect by interrupting cell replication and tumour growth either by intercalation into DNA or interference with topoisomerase II or by generation of reactive oxygen species), neither it nor its metabolites readily pass the blood–brain barrier (BBB).…”