Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease

INTRODUCTION

Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.

METHODS

We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), and plasma biomarker analysis: phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and brain-derived neurotrophic factor (BDNF).

RESULTS

After adjusting for demographics, apolipoprotein E (APOE) ε4 status, cognition, and comorbidities, the highest tertile of REM latency was associated with higher Aβ burden (β = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.002), elevated p-tau181 (β = 0.19, 95% CI: 0.02 to 0.13, p = 0.002), and reduced BDNF levels (β = -0.47, 95% CI: –0.68 to –0.13, p = 0.013), compared to the lowest tertile.

DISCUSSION

Prolonged REM latency may serve as a novel marker or risk factor for AD/ADRD pathogenesis.

Highlights

• Rapid eye movement latency (REML) may be a potential marker for Alzheimer's disease and Alzheimer's disease and related dementias (AD/ADRD) pathogenesis.
• Prolonged REML was associated with higher amyloid beta (Aβ) burden, phosphorylated tau-181 (p-tau181), and lower brain-derived neurotrophic factor (BDNF) levels.
• Intervention trial is needed to determine if targeting REML can modify AD/ADRD risk.
• Slow-wave sleep was not associated with AD/ADRD biomarkers.