Developmental trajectory of the coupling between CSF and cerebral hemodynamics across human lifespan

2605 

Abstract Submission 

Lin Hua¹, Canpeng Huang¹, Zhen Yuan¹, Zhiying Zhao¹

¹University of Macau, Taipa, Macau

Lin Hua  
University of Macau
Taipa, Macau

Canpeng Huang  
University of Macau
Taipa, Macau

Zhen Yuan  
University of Macau
Taipa, Macau

Zhiying Zhao  
University of Macau
Taipa, Macau

The lymphatic system of brain, known as glymphatic system, plays an important role in waste clearance and maintaining the water homeostasis of the central nervous system. Recent studies have reported that the movement of the cerebrospinal fluid (CSF) in the ventricles during slow-wave sleep, which are coupled with high-amplitude spontaneous brain activations, contributes to increased metabolite transportation and clearance [1, 2]. This phenomenon, hereinafter referred to as the CSF-BOLD coupling, is also present in the wakeful brain and has been associated with aging and neurodegenerative diseases [3]. However, no reference standards currently exist to quantify the glymphatic function over time using this measurement as a proxy, which hinders the understanding of the glymphatic changes across the human lifespan. Therefore, the current study aims to elucidate the developmental trajectory of CSF-BOLD coupling across the lifespan.

A total of 2159 subjects with the age span from 5 to 100 years were retrieved from three Human Connectome Project (HCP) datasets, including HCP Development (HCP-D; n = 628; age range: 5-21), HCP Young Adult (HCP-YA; n = 811; age range: 22-35) and HCP Aging (HCP-A; n = 720; age range: 36-100). After image preprocessing, the global BOLD signal and the CSF inflow signal were extracted from the gray matter mask and the bottom slice of CSF mask, respectively. Cross-correlation analysis was performed to measure the coupling strength between the global BOLD signal and the CSF inflow signal (Figure 1). Then, the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modelling with fractional polynomials was used to model the changes in CSF-BOLD coupling strength and brain structural measures across the lifespan separately. Finally, correlation analysis was conducted to examine the relationship between the coupling strengths and brain morphological and behavioral measures.

The CSF-BOLD coupling showed a significantly negative peak at the 3.2-second lag (r = -0.45; p < 0.001, permutation test) across whole subjects. Fitting with fractional polynomials, CSF-BOLD coupling strength presented an initial trend of a steep drop from early childhood (5 years) to early adulthood (peaking around 35 years), followed by an increase till the late life stage (age 90-100) in both sexes (Figure2). This developmental trajectory is similar between males and females with the negative peak arriving earlier in females. In the late adulthood (50-100 years), females showed a significantly stronger CSF-BOLD coupling relationship than males (t = -2.10, p = 0.036). Moreover, the developmental trajectory of intracranial tissue volume and CSF-BOLD coupling suggested that age-related change in CSF-BOLD coupling was in synchrony with the white matter development. Regarding behavioral measures, after adjusting for age and sex, CSF-BOLD coupling strength positively correlated with item scores of hours of actual sleep (r = 0.131, p < 0.001) and frequency of sleep medicine (r = 0.077, p = 0.002) in Pittsburg Sleep Quality Index (PSQI). Finally, CSF-BOLD coupling coefficient was correlated with cognitive function scores assessed by the NIH Toolbox for the Assessment of Neurological Behavior and Function Cognition Battery (NIHTB-CB) adjusted for age. Significant negative correlations are with the working memory domain (r = -0.070, p = 0.003) and total cognition score of NIHTB-CB (r = -0.092, p < 0.001). Both fluid (r = -0.107, p < 0.001) and crystal intelligence (r = -0.067, p = 0.004) score also negatively correlated with CSF-BOLD coupling strength.

In conclusion, the current study contributes to our understanding of the development of the glymphatic system across the lifespan, shedding light on its dynamic changes, gender-specific variations, and associations with sleep quality and cognitive function.

Early life, Adolescence, Aging ²

Cerebral Metabolism and Hemodynamics ¹

Aging

Cerebro Spinal Fluid (CSF)

Development

FUNCTIONAL MRI