Stage-dependent relationship between sleep duration and cortical tau deposition in cognitively impaired individuals: A cross-sectional study

Abstract

Background

Changes in sleep characteristics are critical in the course of Alzheimer's disease (AD).

Objective

We aimed to explore the relationship between sleep duration and tau pathology progression in patients with AD and mild cognitive impairment (MCI).

Methods

This cross-sectional study included 172 patients (70 with MCI and 102 with AD). Sleep duration and disturbances were assessed through standardized questionnaires, while tau deposition and cerebrospinal fluid clearance were evaluated using tau-PET and diffusion tensor image analysis along the perivascular space (DTI-ALPS), along with comprehensive cognitive assessments. The data were adjusted for variables such as demographic factors, clinical symptoms, and medications.

Results

Sleep duration showed a positive association with tau deposition in the MCI stage (total sleep: β = 0.18, p = 0.014; nighttime sleep: β = 0.20, p = 0.007) but negatively associated in the AD stage (total sleep: β = −0.18, p = 0.039; nighttime sleep: β = −0.20, p = 0.039). Patients with sleep disturbances demonstrated lower tau burdens (group difference = 0.62, p = 0.005). Mediation analysis revealed a significant indirect effect of depression in the sleep-tau relationship (total sleep: β = −0.26, p = 0.040; nighttime sleep: β = −0.24, p = 0.040).

Conclusions

This study first revealed the stage-dependent characteristics of sleep-tau relationships, highlighting the MCI stage as a critical research focus.

Clinical Trial

The study was registered with ClinicalTrials.gov (NCT05623124). URL: https://clinicaltrials.gov/study/NCT05623124.