Impact of Chemotherapy on Glymphatic Pathway, Inflammation and Cognitive Function in Breast Cancer
Presented During:
Wednesday, June 25, 2025: 5:45 PM - 7:00 PM
Brisbane Convention & Exhibition Centre
Room:
M3 (Mezzanine Level)
Poster No:
101
Submission Type:
Abstract Submission
Authors:
Xiaoyu Zhou1, Jing Yang2, Jun Chen3, Daihong Liu4, Jiuquan Zhang5
Institutions:
1School of Medicine, Chongqing University, Chongqing, Chongqing, 2Chongqing University Cancer Hospital, Chongqing, chongqing, 3Bayer Healthcare, Wuhan, Wuhan, 4Department of Radiology, Chongqing University Cancer Hospital, Chongqing, chongqing, 5Department of Radiology, Chongqing University Cancer Hospital, chongqing, chongqing
First Author:
Co-Author(s):
Introduction:
Chemotherapy-induced cognitive impairment is a common problem in breast cancer patients, but its underlying mechanism remains unclear. Chemotherapy drugs can induce systemic inflammation, which may impact the nervous system by crossing the blood-brain barrier. The glymphatic system is recently found responsible for waste clearance in the brain, involving four main processes: cerebrospinal fluid (CSF) production, CSF influx into perivascular spaces, substance exchange in the white matter, and waste clearance. MRI techniques can assess these processes using four indicators: choroid plexus volume, volume fraction of perivascular space (PVSVF), volume fraction of free water in white matter (FW-WM), and diffusivity along the perivascular space (ALPS). This study aims to investigate the longitudinal changes in glymphatic function during neoadjuvant chemotherapy in breast cancer patients and explore their relationship with cognitive and inflammatory markers.
Methods:
A total of 113 breast cancer patients were included longitudinally. MRI scans (including T1WI and DKI), cognitive assessments, and blood tests were conducted at three time points: pre-chemotherapy, after one cycle, and post-chemotherapy completion. The choroid plexus of the subjects is automatically delineated in T1WI using a machine learning model. PVSVF is calculated in T1WI using the Frangi filter algorithm. FW-WM and ALPS are computed using DKI sequence. Cognitive assessments includes self-rating anxiety scale (SAS), self-rating depression scale (SDS), digit span test (DST; forward and backward); trail making test part A (TMT-A), verbal fluency test (VFT), functional assessment of cancer therapy-cognitive function (FACT-Cog) with four aspects: perceived cognitive impairments (PCI), comments from others (OTH), perceived cognitive abilities (PCA) and impact on quality of life (QOL). Systemic inflammation indices, determined from the initial complete blood count, includes: neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, systemic immune-inflammatory index (SII), prognostic nutritional index (PNI).
Mixed-effects models were used to examine the changes in MR indicators, cognitive scores, and inflammatory markers at three time points during neoadjuvant chemotherapy, with results corrected using False Discovery Rate (FDR). Significant indicators from the mixed-effects model were further analyzed for correlation and mediation effects.
Mixed-effects models were used to examine the changes in MR indicators, cognitive scores, and inflammatory markers at three time points during neoadjuvant chemotherapy, with results corrected using False Discovery Rate (FDR). Significant indicators from the mixed-effects model were further analyzed for correlation and mediation effects.
·Figure 1
Results:
Choroid plexus volume (b = 0.010, P < 0.001) increased after chemotherapy, while PVSVF (b = –0.026, P = 0.20), FW-WM (b < 0.001, P = 0.26), and ALPS (b < 0.001, P = 0.94) did not show significant changes. A serious of cognitive scores were abnormal during chemotherapy (SAS, P = 0.018; SDS, P = 0.010; PCI, P < 0.001; OTH, P < 0.001; PCA, P < 0.001; QOL, P = 0.016; FACT-Cog, P < 0.001). And nutritional prognostic indicator (PNI, calculated by (Albumin + 5) × L) were decreased after chemotherapy (b = –0.026, P < 0.001). Correlation analysis revealed a negative correlation between choroid plexus volume and PNI (r = –0.226, P < 0.001), and a positive correlation between PNI and perceived cognitive abilities (r = 0.113, P = 0.048). Mediation analysis showed that PNI mediated the relationship between chemotherapy-induced changes in SDS (95% CI [–0.162, –0.020], P < 0.001) and choroid plexus volume (95% CI [–0.002, –0.010], P < 0.001).
·Figure 2
Conclusions:
During neoadjuvant chemotherapy, breast cancer patients experience glymphatic dysfunction in the CSF production process, which may be mediated by the inflammatory marker PNI. This finding provides insight into the mechanisms of chemotherapy-induced brain changes and may facilitate early detection and intervention.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Novel Imaging Acquisition Methods:
Multi-Modal Imaging 2
Keywords:
Cerebro Spinal Fluid (CSF)
Cognition
MRI
Therapy
Other - Glymphatic system
1|2Indicates the priority used for review
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Jiang, D. (2023). Regional glymphatic abnormality in behavioral variant frontotemporal dementia. Annals of Neurology, 94(3), 442–456. https://doi.org/10.1002/ana.26710
Lin, S. (2024). Association of MRI indexes of the perivascular space network and cognitive impairment in patients with obstructive sleep apnea. Radiology, 311(3), e232274. https://doi.org/10.1148/radiol.232274
Rajagopalan, S. (2024). Mineralocorticoid receptor antagonism prevents aortic plaque progression and reduces left ventricular mass and fibrosis in patients with type 2 diabetes and chronic kidney disease: The MAGMA trial. Circulation, 150(9), 663–676. https://doi.org/10.1161/CIRCULATIONAHA.123.067620
Ray, N. J. (2023). Free-water imaging of the cholinergic basal forebrain and pedunculopontine nucleus in parkinson’s disease. Brain, 146(3), 1053–1064. https://doi.org/10.1093/brain/awac127
Tonietto, M. (2023). Periventricular remyelination failure in multiple sclerosis: A substrate for neurodegeneration. Brain: A Journal of Neurology, 146(1), 182–194. https://doi.org/10.1093/brain/awac334
Xie, L. (2024). Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study. NeuroImage, 288, 120524. https://doi.org/10.1016/j.neuroimage.2024.120524