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 Dai1,3 

1Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, 215006, People’s Republic of China

Correspondence: Hui Dai, Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Email huizi198208@126.com

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, sleep disorders, glymphatic system, diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), mediation analysis