REM Sleep Delay Tied to Higher Levels of Amyloid, Tau in Cognitive Impairment

Delayed rapid eye movement sleep latency (REML) is associated with Alzheimer disease (AD) pathophysiologic changes in patients with AD and cognitive impairment, according to study results published in the journal Alzheimer’s & Dementia.

Researchers conducted a cross-sectional study at a single outpatient neurology unit in China from 2022 to 2023 to investigate the association between polysomnography (PSG)-assessed REM sleep features and 3 plasma biomarkers for AD in patients aged 50 years and older. All participants underwent cognitive testing prior to enrollment and were classified as having AD, mild cognitive impairment (MCI), or normal cognition.

Individuals with sleep-related breathing disorders, neurodegenerative diseases other than AD, major psychiatric disorders, severe systemic disease, or other significant neurologic disorders were excluded, as were individuals who use antipsychotic or sedative-hypnotic drugs.

All participants underwent positron emission tomography (PET) scans and overnight PSG; plasma concentrations of phosphorylated tau at threonine 181 (p-tau181), neurofilament light chain (NfL), and brain-derived neurotrophic factor (BDNF) were assessed. Spearman correlation analysis and linear regression models were employed for statistical analysis.

A total of 128 participants (AD, n=64; MCI, n=41; normal cognition, n=23) were included in the study (mean age, 70.8 years; women, 56.9%). Individuals with AD had lower scores on the Mini-Mental State Examination (MMSE) and represented a higher proportion of APOE4 carriers. Compared with individuals with normal cognition, those with MCI or AD had longer REML, longer sleep onset latency (SOL), and lower slow-wave sleep (SWS) percentages, but the differences did not attain statistical significance.

REML was shown to be significantly correlated with BDNF (P =.007) and amyloid beta PET standardized uptake value ratio (SUVR) (P =.013). Participants in the highest (>192.7 min) vs lowest (<98.2 min) tertiles of REML showed significantly higher levels of p-tau181, higher amyloid beta PET SUVR, and lower BDNF levels.

In addition, those with the highest (13.9%) vs lowest (≤9.0%) tertiles of REM percentage had significantly lower levels of p-tau181. Results were consistent after adjusting for age and sex.

After further adjustments for APOE4 status, diabetes mellitus, smoking, body mass index (BMI), antidepressant use, and MMSE score, REML was again statistically associated with higher p-tau181, amyloid beta SUVR, and lower BDNF. Lower REM and SWS percentages were also associated with higher levels of p-tau181.

No significant association was observed between other sleep measures and AD and AD-related dementia biomarkers (AD/ADRD). Sensitivity analysis showed that the associations of REML with amyloid beta PET SUVR and BDNF levels remained significant, while the associations between lower REM percentage and SWS percentage with higher p-tau181 levels did not remain significant.

Study limitations included a cross-sectional design, small sample size, the focus on p-tau181 rather than p-tau217 limiting AD pathology input, the influence of a clinical setting on sleep measurement accuracy, and lack of generalizability due to participants’ SWS percentage values.

“Given that these pathological changes typically precede clinical symptoms by a decade or more, our findings may provide novel insights regarding the involvement of REM sleep in the early detection and intervention of AD/ADRD,” the researchers concluded.

Disclosure: Some [or one] study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.