Sleep disorders cause myelin reduction in gray matter mediated by glymphatic system dysfunction
Poster No:
2578
Submission Type:
Abstract Submission
Authors:
Christina Andica1,2, Koji Kamagata2, Kaito Takabayashi2, Zaimire Mahemuti2, Akifumi Hagiwara2, Shigeki Aoki1,2
Institutions:
1Faculty of Health Data Science, Juntendo University, Chiba, Japan, 2Department of Radiology, Juntendo University, Tokyo, Japan
First Author:
Christina Andica
Faculty of Health Data Science, Juntendo University|Department of Radiology, Juntendo University
Chiba, Japan|Tokyo, Japan
Faculty of Health Data Science, Juntendo University|Department of Radiology, Juntendo University
Chiba, Japan|Tokyo, Japan
Co-Author(s):
Shigeki Aoki
Faculty of Health Data Science, Juntendo University|Department of Radiology, Juntendo University
Chiba, Japan|Tokyo, Japan
Faculty of Health Data Science, Juntendo University|Department of Radiology, Juntendo University
Chiba, Japan|Tokyo, Japan
Introduction:
Emerging evidence suggests that sleep deprivation alters gray matter (GM) microstructure (Voldsbekk, Bjornerud et al. 2022) and impairs the glymphatic system, a brain-wide perivascular network crucial for clearing central nervous system waste (Hablitz, Pla et al. 2020, Mestre, Mori et al. 2020), as indicated by the diffusion tensor Imaging analysis along the perivascular space (DTI-ALPS) index (Siow, Toh et al. 2022). Nevertheless, the relationship between GM microstructural changes and with glymphatic efficiency in sleep disorders, remain elusive. Our proposed study aims to utilize magnetization transfer (MT) imaging and neurite orientation dispersion and density imaging (NODDI) to elucidate the GM microstructural changes, and the DTI-ALPS index to assess glymphatic function in older adults with sleep disorders.
Methods:
In the present study, we evaluated 50 individuals with sleep disorders (24 males; aged 71.08 ± 4.69 years; Pittsburgh sleep quality index [PSQI] >5] and 50 individuals without sleep disorders [24 males; 73.04 ± aged 5.80 years; PSQI ≤5) who has participated in the Bunkyo Health Study (Someya, Tamura et al. 2019). MT imaging (to obtain myelin volume fraction [MVF]) and diffusion-weighted imaging (to obtain NODDI metrics [b-values of 1000 and 2000 s/mm²] and ALPS index [b-value of 1000 s/mm²]) for all study participants were performed using a 3 T MAGNETOM Prisma system (Siemens Healthcare, Erlangen, Germany) equipped with a 64-channel head coil. GM was parcellated using the Desikan-Killiany atlas and overlaid onto the GM-based spatial statistics skeleton (Ball, Srinivasan et al. 2013), to exclude any white matter and cerebrospinal fluid voxels. Median values for MVF, NDI, ODI, and ISO were measured from 34 cerebral cortices, cerebellar cortex, and seven subcortical regions on the left and right hemispheres (42 regions of interest [ROIs]). The ALPS index was calculated with a validated semiautomated pipeline (Taoka, Ito et al. 2022). The ALPS index, MVF, and NODDI measures (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]) were compared between groups using a general linear model (GLM), adjusting for age, sex, years of education, and intracranial volume as covariates. An false discovery rate (FDR)-corrected (42 ROIs) P-value <0.05 was considered significant. Multivariate linear regression (MLR), considering these covariates, assessed the relationship between the ALPS index and MVF in GM areas with significant differences between the sleep-disordered and non-sleep-disordered groups. Finally, the PROCESS Procedure for SPSS Version 4.2 was employed for mediation analysis to investigate the relationship between the PSQI, ALPS index, and GM MVF in those areas.
Results:
Individuals with sleep disorders exhibited a significantly lower ALPS index (1.37 ± 0.17, P = 0.026) compared to those without sleep disorders (1.44 ± 0.16). Additionally, a significantly lower MVF, with FDR-corrected P-values ranging from 0.010 to 0.049, was also observed in the sleep-disordered group across GM regions (Table 1). MLR analyses demonstrated positive associations between the ALPS index and GM MVF values, with standardized β ranging from 0.313 to 0.639 (P = 0.00059 to 0.033). Mediation analysis revealed an indirect effect of the PSQI total on GM MVF mediated by the ALPS index in GM areas that were significant in the MLR analyses (Figure 1). However, GLM analysis showed no significant findings for NDI, ODI, and ISO. Moreover, MLR and mediation analyses yielded no significant results for individuals without sleep disorders.
Conclusions:
Our findings using multimodal MRI-based measures indicated that individuals with sleep disorders exhibited reduced diffusivity along perivascular spaces, as measured by the ALPS index, and showed demyelination in the GM, in contrast to those without such disorders. Mediation analysis also suggested glymphatic dysfunction as a possible mediator between sleep disorders and GM demyelination.
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Multivariate Approaches 2
Perception, Attention and Motor Behavior:
Sleep and Wakefulness 1
Keywords:
ADULTS
Cortex
Demyelinating
Multivariate
Myelin
Sleep
Statistical Methods
1|2Indicates the priority used for review
Provide references using author date format
Hablitz, L. (2020), 'Circadian control of brain glymphatic and lymphatic fluid flow', Nat Commun, vol. 11, no. 1, pp. 4411.
Mestre, H. (2020), 'The Brain's Glymphatic System: Current Controversies', Trends Neurosci, vol. 43, no. 7, pp. 458-466.
Siow, T. Y. (2022), 'Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults', Neurology, vol. 98, no. 8, pp. e829-e838.
Someya, Y. (2019), 'Skeletal muscle function and need for long-term care of urban elderly people in Japan (the Bunkyo Health Study): a prospective cohort study', BMJ Open, vol. 9, no. 9, pp. e031584.
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