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. 2025 Feb;21(2):e14495.
doi: 10.1002/alz.14495. Epub 2025 Jan 27.

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

Jiangli Jin  1   2 , Jiong Chen  3 , Clémence Cavaillès  4 , Kristine Yaffe  4   5 , Joseph Winer  6 , Laura Stankeviciute  7 , Brendan P Lucey  8 , Xiao Zhou  9 , Song Gao  3 , Dantao Peng  2   10 , Yue Leng  4
Affiliations

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

Jiangli Jin et al. Alzheimers Dement. 2025 Feb.

Abstract

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.

Keywords: Alzheimer's disease; amyloid beta; biomarker; polysomnography; rapid eye movement latency; sleep.

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Conflict of interest statement

Dr. Lucey discloses funding from the National Institutes of Health, Eisai, and Good Ventures/Open Philanthropy that are outside the scope of this work. Dr. Lucey also discloses consulting for Merck, Eli Lilly, Eisai, OrbiMed, and GLG Consulting, as well as honoraria from the BrightFocus Foundation, the Weston Brain Institute, Eli Lilly, and Beacon Biosignals that are outside the scope of this work. All other authors declare not competing interests. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Scatter matrix plots of AD/ADRD biomarkers and sleep architectures. Correlations were calculated using the Spearman correlation coefficient, where * indicated p < 0.05; ** indicated p < 0.01; and *** indicated p < 0.001. Aβ PET used SUVR values. Aβ PET, amyloid beta positron emission tomography; AD/ADRD, Alzheimer's disease and Alzheimer's disease and related dementias; BDNF, brain‐derived neurotrophic factor; NfL, neurofilament light; p‐tau181, phosphorylated tau protein at threonine 181; REM, rapid eye movement; REML, REM latency; SUVR, standardized uptake value ratio; SWS, slow‐wave sleep.
FIGURE 2
FIGURE 2
Natural spline regression analysis of REML and AD/ADRD biomarkers. Model was adjusted for age, sex, APOE ε4 status, DM, smoking, MMSE score, antidepressant use, and BMI. The blue line represents the fitted values from the natural spline regression, with shaded areas indicating the 95% confidence intervals. Non‐linear p‐values are shown above each plot. Aβ PET, amyloid beta positron emission tomography; AD/ADRD, Alzheimer's disease and Alzheimer's disease and related dementias; APOE, apolipoprotein E; BDNF, brain‐derived neurotrophic factor; MMSE, Mini‐Mental Status Examination; NfL, neurofilament light; p‐tau181, phosphorylated tau protein at threonine 181; REM, rapid eye movement; REML, REM latency.
See this image and copyright information in PMC

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