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. 2024 Dec 23:16:2205-2215.
doi: 10.2147/NSS.S496607. eCollection 2024.

Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Demonstrates That Sleep Disorders Exacerbate Glymphatic Circulatory Impairment and Cognitive Impairment in Patients with Alzheimer's Disease

Yi Shang  1 , Lefan Yu  1 , Hanqi Xing  1 , Yue Chang  1 , Ke Dong  1 , Yao Xiao  1 , Yuanqing Liu  1 , Mengmeng Feng  1 , Yiren Qin  2 , Hui Dai  1   3
Affiliations

Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Demonstrates That Sleep Disorders Exacerbate Glymphatic Circulatory Impairment and Cognitive Impairment in Patients with Alzheimer's Disease

Yi Shang et al. Nat Sci Sleep. .

Abstract

Objective: Sleep disorders are common in Alzheimer's disease (AD) patients and can impair the glymphatic system, leading to cognitive decline. This study aimed to investigate whether AD patients with sleep disorders exhibit worse glymphatic function and more severe cognitive impairment compared to those without sleep disorders and to explore the underlying molecular imaging mechanisms.

Methods: This study included 40 AD patients with sleep disorders (ADSD), 39 cognitively matched AD patients without sleep disorders (ADNSD), and 25 healthy middle-aged and elderly controls (NC). Participants underwent functional magnetic resonance imaging (fMRI), and cognitive and sleep assessments. The ALPS (Along the Perivascular Space) index was calculated, followed by intergroup comparisons, correlation analyses, and mediation analyses. The diagnostic utility of the ALPS index was assessed using a receiver operating characteristic (ROC) curve.

Results: The ALPS index was lower in the ADNSD and ADSD groups compared to the NC group. In the ADSD group, PSQI scores were negatively correlated with MMSE scores. The ALPS index was positively correlated with MMSE scores and negatively with PSQI scores. Mediation analyses indicated that the ALPS index partially mediated the effect of sleep disturbances on cognitive impairment (indirect effect = -0.134; mediation effect = 30.505%). The area under the ROC curve (AUROC) for distinguishing ADSD from ADNSD was 0.86, with a cutoff ALPS index value 1.309.

Conclusion: Sleep disorders worsen glymphatic function and cognitive impairment in AD patients. The ALPS index partially mediates the impact of sleep disorders on cognitive function and shows moderate accuracy in distinguishing between patients with ADSD and ADNSD.

Keywords: Alzheimer’s disease; diffusion tensor imaging analysis along the perivascular space (DTI-ALPS); glymphatic system; mediation analysis; sleep disorders.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Research flowchart.
Figure 2
Figure 2
Calculation of Alps index. Dxxproj is the diffusion rate along the X-axis in the projection fiber, Dxxassoc is the diffusion rate along the X-axis in the association fiber, Dyyproj is the diffusion rate along the Y-axis in the projection fiber, and Dzzassoc is the diffusion rate along the Z-axis in the association fiber.
Figure 3
Figure 3
Difference of the Alps-index between groups. ALPS-index cut-off of 1.309; ****p < 0.0001.
Figure 4
Figure 4
Correlation Analysis of Alps-index with neuropsychological scales in ADSD patients. (A) Correlation between PSQI score and MMSE score; (B) Correlation between ALPS index and MMSE score; (C) Correlation between PSQI score and ALPS index.
Figure 5
Figure 5
Mediation analysis. A mediation analysis based on SPSS Model 4, with gender, age, years of education, and APOE4 gene carrier status as covariates.
Figure 6
Figure 6
The ROC curve of Alps index distinguishing ADSD and ADNSD.
See this image and copyright information in PMC

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