Objective:

This study aims to characterize associations between sleep quality, proxies of glymphatic flow, and executive function among cancer survivors, identifying modifiable factors and mechanisms of action for CRCI.

Background:

Cancer-Related Cognitive Impairment (CRCI) is commonly experienced by cancer survivors. Sleep disorders, such as obstructive sleep apnea (OSA), are prevalent among patients with CRCI and impair executive function. Glymphatic dysfunction has been associated with cognitive impairment in sleep disorders and can be approximated by measuring enlarged perivascular spaces (ePVS), cerebral microbleed burden (CMB), white matter hyperintensities (WMH), and ventricular size on routine brain MRI. Our registry previously identified ventriculomegaly and sleep disorders contributed to CRCI.

Design/Methods:

Data was extracted from a clinical registry at the Cancer Cognitive Clinic. 110 CRCI patients were included, excluding those with primary CNS malignancies. Sleep quality was assessed using the Sleep Disruption Severity score of the Pittsburgh Sleep Quality Index and with Nocturnal Polysomnography. OSA severity was measured using the Apnea-Hypopnea Index. Executive function was assessed using the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and NIH Toolbox batteries. MRI was analyzed to obtain measures of glymphatic dysfunction including WMH severity, microbleed presence, and ePVS severity. 

Results:

The results controlled for age because as age increased, processing speed decreased (β=-1.75,p=0.054). Processing speed was inversely related to PVS burden (β =-1.83,p=0.018) and increasing OSA severity (β=-6.29,p=0.013). Sustained attention and inhibition scores were inversely related to ventricle size (β=-2.14,p =0.03), WMH presence (β=-1.71,p=0.03), and increasing OSA severity (β=-6.29,p=0.013). Phonemic fluency scores were inversely related to the presence of cerebral microbleeds (β =-0.96,p=0.055).  

Conclusions:

The inverse relationship between processing speed, sustained attention, and phonemic fluency scores, with ePVS, CMB, and ventricle size, suggests that glymphatic flow may mediate CRCI. Future directions include understanding how treatment of sleep disorders may prevent, modify, or reverse cognitive and imaging changes.