Longer REM latency correlates with increased AD biomarkers, highlighting potential new diagnostic marker.
Study: Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease. Image Credit: Small365/Shutterstock.com
In a recent study published in Alzheimer’s & Dementia, researchers assessed the relationship between sleep architecture and biomarkers of Alzheimer’s disease (AD) and related dementias (ADRDs).
Background
Sleep disturbances are prevalent in dementia patients and have been increasingly associated with AD/ADRD biomarkers. Evidence suggests that sleep quality, duration, and excessive daytime sleepiness are associated with amyloid-β (Aβ) deposition in older adults.
One study reported associations between sleep deprivation and elevated Aβ levels in the brain, especially in the thalamus and hippocampus, which are critical regions involved in AD pathogenesis.
Slow-wave sleep (SWS), the deepest stage of sleep, has received considerable attention for its role in glymphatic clearance (of metabolic waste) and memory consolidation.
Age-related SWS reductions are reportedly associated with an elevated risk of incident dementia. Nonetheless, which aspects of sleep are the most relevant to AD/ADRD pathophysiology remains debatable.
About the study
In the present study, researchers investigated associations between sleep architecture and AD/ADRD biomarkers. They recruited individuals aged ≥ 50 years from the neurology unit of the China-Japan Friendship Hospital in China.
People with sleep-related breathing or movement disorders, use of sedative-hypnotics or antipsychotic drugs, other neurodegenerative diseases besides AD, or other psychiatric conditions besides anxiety and depression were excluded.
Participants underwent a comprehensive diagnostic process, including symptom evaluation, neurological and physical examinations, magnetic resonance imaging, and cognitive and laboratory tests. Blood samples were collected for biomarker measurements.
AD/ADRD biomarkers were apolipoprotein E (APOE) ε4 carrier status, brain-derived neurotrophic factor (BDNF), neurofilament light (NFL), and phosphorylated tau (p-tau) at threonine 181 (p-tau181).
Real-time fluorescence quantitative polymerase chain reaction was performed to determine APOE ε4 status, and the presence of at least one ε4 allele was deemed as APOE ε4-positive.
18F-florbetapir positron-emission tomography (PET) imaging was performed to assess Aβ plaque deposition. All subjects underwent an overnight polysomnography (PSG).
PSG parameters included sleep efficiency (SE), rapid eye movement (REM) latency (REML), total sleep time (TST), sleep onset latency (SOL), and percentages of time spent in non-REM stage 1 (N1), N2, N3 or SWS, and REM.
The researchers used chi-squared and Kruskal-Wallis tests to compare differences in categorical and continuous variables among participants with normal cognition (NC), mild cognitive impairment (MCI), and AD.
Univariable and multivariable linear regression analyses assessed associations between sleep parameters and biomarkers.
Analyses were initially adjusted for sex and age and subsequently for APOE ε4 status, smoking, body mass index (BMI), mini-mental state examination (MMSE) score, and diabetes mellitus. Sleep parameter tertiles were examined to explore non-linear relationships further.
Findings
The study recruited 128 individuals aged 70.8 years, on average. All participants were Han Chinese, 57% were females, 64 were diagnosed with AD, 41 had MCI, and 23 had NC. AD patients had a higher proportion of APOE ε4 carriers and lower MMSE scores.
Individuals with AD or MCI had lower SWS percentages and longer SOL and REML than those with NC, albeit statistically insignificant. There was a significant correlation of REML with Aβ deposition and BDNF.
Participants in the highest tertile of REML had significantly elevated levels of p-tau181, lower BDNF, and higher Aβ deposition than those in the lowest tertile. In addition, individuals in the highest tertile of REM percentage showed significantly reduced p-tau181.
Sex- and age-adjusted analyses yielded consistent findings; in analyses with additional adjustments, REML was significantly associated with increased p-tau181 and lower BDNF.
Lower SWS and REM percentages were associated with elevated p-tau181. In sensitivity analyses, the associations between REML and BDNF and Aβ burden retained significance after correction for false discovery rate, while those of lower SWS and REM percentages with higher p-tau181 levels were no longer sustained.
Further, the associations of REML with AD/ADRD biomarkers were independent of SOL, SE, and TST.
Conclusions
In sum, the findings indicate an association of prolonged REML with a higher Aβ burden, lower BDNF, and elevated p-tau181 in middle-aged and older adults across AD continuums. These associations were significant even after adjustments for various confounders.
Given that these pathological changes precede clinical symptoms, prolonged REML could be an early neurodegeneration marker. Further studies are needed to assess whether targeting REML could modify AD/ADRD risk.
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