Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder

Ren, Cheng; Li, Peipei; Li, Jing; Li, Yaqiang; Zhang, Lijun; Chen, Guihai; Dong, Fangyi; Hu, Dong; Zhang, Mei

doi:10.5664/jcsm.9574

Cited by 6 publications

(5 citation statements)

References 69 publications

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“…Neurofilament light chain may be associated with sleep disturbance, but the literature has shown contradictory findings. Middle-aged insomnia patients have higher NfL levels compared to those without insomnia ( Zhang et al, 2018 ; Ren et al, 2022 ), and one study reported decreased NfL levels after treatment ( Zhang et al, 2018 ). In another study, higher NfL levels were associated with worse subjective sleep quality, and decreased sleep duration, sleep efficiency, and REM sleep ( Zhang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…In patients with multiple sclerosis, higher serum NfL levels were also associated with lower sleep efficiency in addition to lower NREM sleep contribution ( Sacmaci et al, 2020 ). However, another study in chronic insomnia did not show associations with subjective sleep quality ( Ren et al, 2022 ). Serum NfL levels have been found to positively correlate with the apnea, hypopnea and 4%-oxygen desaturation indices in addition to the percent of total sleep time with oxyhemoglobin saturation below 90%, but these correlations were mostly driven by moderate-to-severe OSA patients ( Arslan et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Carvalho

Louis

Przybelski

et al. 2022

Front. Aging Neurosci.

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IntroductionSleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer’s disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline.MethodsIn this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aβ42, p-tau, p-tau/Aβ42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea.ResultsHigher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001–0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002–0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aβ42 only in participants with an abnormal ratio (>0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001–0.012], p = 0.021) increase in the log of CSF p-tau/Aβ42.ConclusionSleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aβ42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Carvalho

Louis

Przybelski

et al. 2022

Front. Aging Neurosci.

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“…The mechanisms underlying the associations between NfL and post-stroke mental health disorders could be multifactual and have not been thoroughly illustrated. NfL is also found to be increased in other psychiatric disorders, such as bipolar disorders (30), chronic insomnia disorder (29), and depression not due to stroke (31). These findings suggest that mental health disorders might contribute to neuronal damage, thus promoting the increase of NfL.…”

Section: Discussionmentioning

confidence: 76%

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Wang

Guo

et al. 2022

Front. Psychiatry

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BackgroundMental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients.MethodsThis study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems.ResultsThe high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)].ConclusionsThese findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS.

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“…The free therapy group of patients had lower cognitive performance scores measured by the Montreal Cognitive Assessment (MoCA) test compared to controls and those who underwent therapy ( 52 ). A different study found that levels of serum NfL and leukocyte telomere shortening (used as an aging marker) had been associated with female chronic insomnia patients' total sleep time, sleep efficiency, and sleep quality, measured by the Pittsburgh Sleep Quality Index ( 53 ). Contrarily, NF levels were not informative in narcolepsy type I, and sleep quality assessment, which was measured by the Medical Outcomes Study Sleep Scale, was altered in patients with Alzheimer's disease, suggesting an important role of sleep loss in NF alternations ( 54 , 55 ).…”

Section: Neurofilaments In Sleepmentioning

confidence: 99%

Shedding light on neurofilament involvement in cognitive decline in obstructive sleep apnea and its possible role as a biomarker

Jaromirska,

Kaczmarski,

Strzelecki

et al. 2023

Front. Psychiatry

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Obstructive sleep apnea is one of the most common sleep disorders with a high estimated global prevalence and a large number of associated comorbidities in general as well as specific neuropsychiatric complications such as cognitive impairment. The complex pathogenesis and effects of the disorder including chronic intermittent hypoxia and sleep fragmentation may lead to enhanced neuronal damage, thereby contributing to neuropsychiatric pathologies. Obstructive sleep apnea has been described as an independent risk factor for several neurodegenerative diseases, including Alzheimer's disease and all-cause dementia. The influence of obstructive sleep apnea on cognitive deficits is still a topic of recent debate, and several mechanisms, including neurodegeneration and depression-related cognitive dysfunction, underlying this correlation are taken into consideration. The differentiation between both pathomechanisms of cognitive impairment in obstructive sleep apnea is a complex clinical issue, requiring the use of multiple and costly diagnostic methods. The studies conducted on neuroprotection biomarkers, such as brain-derived neurotrophic factors and neurofilaments, are recently gaining ground in the topic of cognition assessment in obstructive sleep apnea patients. Neurofilaments as neuron-specific cytoskeletal proteins could be useful non-invasive indicators of brain conditions and neurodegeneration, which already are observed in many neurological diseases leading to cognitive deficits. Additionally, neurofilaments play an important role as a biomarker in other sleep disorders such as insomnia. Thus, this review summarizes the current knowledge on the involvement of neurofilaments in cognitive decline and neurodegeneration in obstructive sleep apnea patients as well as discusses its possible role as a biomarker of these changes.

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Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder

Cited by 6 publications

References 69 publications

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Shedding light on neurofilament involvement in cognitive decline in obstructive sleep apnea and its possible role as a biomarker

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