Basal Forebrain Atrophy and Glymphatic Dysfunction in Subjective Cognitive Decline
Poster No:
181
Submission Type:
Abstract Submission
Authors:
yitong li1, Yanlin Yu2, Chengyi Yuan2, Kai-Hsiang Chuang3, Qihao Guo4, Chu-Chung Huang5
Institutions:
1East China Normal University, Shanghai, China, 2East China Normal University, Shanghai, Asia, 3The University of Queensland, Brisbane, Queensland, 4Department of Gerontology, Shanghai Sixth People’s Hospital, Shanghai, China, 5East China Normal Univerisity, Shanghai, China
First Author:
Co-Author(s):
Introduction:
Individuals with subjective cognitive decline (SCD) are considered at increased risk for objective cognitive decline and dementia, but the underlying neurobiological mechanisms remain unclear. Recent studies have shown that SCD shares pathological characteristic with Alzheimer's Disease (AD), particularly the accumulation of amyloid-β (Aβ). Growing evidence supports the critical role of glymphatic system in clearing Aβ and impaired glymphatic function has been associated with poorer cognitive performance in SCD (Li et al., 2024). Although a recent research suggests a link between cholinergic pathways and glymphatic clearance, the reasons behind glymphatic dysfunction in SCD remain unknown. Here, we aim to investigate the potential impact of basal forebrain volume, a key region of cholinergic pathway, on glymphatic function using noninvasive neuroimaging techniques, including diffusion tensor imaging along the perivascular space (DTI-ALPS) index (Taoka et al., 2017) and the coupling between blood-oxygen level-dependent (BOLD) signals from cortical gray matter and CSF signals (BOLD-CSF coupling) (Fultz et al., 2019). We hypothesize that the reduced basal forebrain volume in SCD influences glymphatic function, which in turn contributes to subjective cognition decline.
Methods:
A total of 88 patients, including 48 subjective cognitive decline (SCD) and 40 cognitively normal controls (NCs) were included in this study. Individual high-resolution T1-weighted images were processed using the computational anatomy toolbox (CAT12), all normalized modulated gray matter tissue segments were used for basal forebrain (BF) volume estimation via a well-validated stereotactic BF atlas (Zaborsky et al., 2008). For glymphatic function measurements, the mean BOLD signal was extracted from cortical gray matter regions and defined as the global BOLD signal following previous study (Han et al., 2021). Cerebrospinal fluid (CSF) signals were extracted from the bottom slices of fMRI acquisition to maximize sensitivity to CSF inflow effect, as illustrated in Figure 1. To calculate DTI-ALPS index, two 5-mm-diameter spherical region of interests (ROI) were placed in the projection fibers and association fibers areas on the FA template. The diffusivities along the x-axis (Dxx), y-axis (Dyy), and z-axis (Dzz) of each ROI were recorded. The DTI-ALPS index was derived by dividing the apparent diffusivity induced by the perivascular space (PVS) flow along medullary vein direction (x-axis) by the diffusivity unaffected by PVS flow (y-axis and z-axis), as shown in Figure 1. Finally, correlation analyses were conducted to investigate the associations between basal forebrain volume, DTI-ALPS index and BOLD-CSF coupling across groups. Mediation analyses were further performed to explore the role of BF volume and glymphatic function in cognitive decline.
Results:
Participants in the SCD group showed significant reductions in basal forebrain volumes, with the most pronounced changes observed in the Ch4 subdivision (Table 1). These BF volume reductions were associated with reduced glymphatic function, as indicated by a decrease of DTI-ALPS index and an increase of BOLD-CSF coupling. Notably, these associations showed interactive effects across the two groups (Figure 2). However, glymphatic function did not mediate the relationship between basal forebrain volume and cognitive decline.
Conclusions:
This study suggests that SCD participants showed a reduction in BF volumes, which were associated with impaired glymphatic functions. However, the mediation analysis did not reach statistical significance, possibly due to the lack of objective differences in cognitive scores between SCD and NC groups. Current findings suggest that early glymphatic system dysfunction may occur at the SCD stage, potentially contributing to subsequent Aβ accumulation and progression toward AD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Task-Independent and Resting-State Analysis
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 2
Keywords:
Cerebro Spinal Fluid (CSF)
Cognition
Degenerative Disease
Other - Glymphatic Dysfunction; Basal Forebrain
1|2Indicates the priority used for review
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Han, F., Chen, J., Belkin-Rosen, A., Gu, Y., Luo, L., Buxton, O. M., Liu, X., & the Alzheimer’s Disease Neuroimaging Initiative. (2021). Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease–related pathology. PLOS Biology, 19(6), e3001233.
Li, Y., Wang, L., Zhong, J., Xu, H., Han, Y., Alzheimer’s Disease Neuroimaging Initiative, Zuo, C., & Jiang, J. (2024). Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study. Alzheimer’s & Dementia, 20(9), 6542-6555.
Taoka, T., Masutani, Y., Kawai, H., Nakane, T., Matsuoka, K., Yasuno, F., Kishimoto, T., & Naganawa, S. (2017). Evaluation of glymphatic system activity with the diffusion MR technique: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Japanese Journal of Radiology, 35(4), 172-178.
Zaborszky, L., Hoemke, L., Mohlberg, H., Schleicher, A., Amunts, K., & Zilles, K. (2008). Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain, 42(3), 1127-1141.