Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI).

Abstract

12091 Background: Cancer survivors often experience cognitive changes, formally known as Cancer-Related Cognitive Impairment (CRCI), during or after treatment. CRCI commonly consists of executive dysfunction, which includes impairments in short-term memory, sustained attention/inhibitory control, cognitive flexibility, processing speed, and top-down processing. CRCI may be impacted by comorbidities and can increase neurodegenerative disease risk. Sleep disorders and disruptions (SDs) impair executive function in the general population. SDs may contribute to CRCI by impeding progression to deep sleep stages associated with enhanced glymphatic flow (GF) and clearance of inflammatory byproducts, leading to ventriculomegaly (VM- enlarged ventricles). VM is associated with cognitive impairment in other disorders, such as normal pressure hydrocephalus. Using data from the University of Cincinnati Cancer Cognitive Registry, we investigated relationships between the incidence and type of SD in CRCI, SDs and executive dysfunction, and evidence of altered GF in SD as measured by Evans Indices (EIs). SDs are known to be prevalent in CRCI patients. We hypothesize that evidence of impaired GF as measured by EIs will be present and associated with SDs and executive dysfunction. Identifying modifiable contributors to CRCI and their mechanisms of action are critical steps towards increasing quality of life in survivors. Methods: 174 patients referred for CRCI between 10/2021-10/2023 underwent assessments for CRCI and sleep hygiene with a cognitive battery, subjective questionnaires, and nocturnal polysomnography. Retrospective data gathered from Epic was entered into a REDCap registry. MRIs were analyzed in McKesson to calculate EIs. Results: Our data demonstrated the presence of SDs in 84% of patients and obstructive sleep apnea in 45%. Measures of apnea severity (apnea-hypopnea index-AHI) and GF (EIs) inversely correlated with executive function scores. This implicates sleep-related GF as a potential mediator of CRCI. Conclusions: CRCI and accompanying increased neurodegenerative risk may be the result of restricted cerebral spinal fluid exchange due to SDs in conjunction with systemic inflammation from cancer and its treatment. Sleep assessments should be routine in CRCI evaluations. Longitudinal assessments will help determine the relationship of SDs and their treatment to the course of CRCI and risk of neurodegenerative disease.