Association Between Obstructive Sleep Apnea and Brain White Matter Hyperintensities in a Population-Based Cohort in Germany

Zacharias, Helena U.; Weihs, Antoine; Habes, Mohamad; Wittfeld, Katharina; Frenzel, Stefan; Rashid, Tanweer; Stubbe, Beate; Obst, Anne; Szentkirályi, András; Bülow, Robin; Berger, Klaus; Fietze, Ingo; Penzel, Thomas; Hosten, Norbert; Ewert, Ralf; Völzke, Henry; Grabe, Hans J.

doi:10.1001/jamanetworkopen.2021.28225

Cited by 33 publications

(21 citation statements)

References 43 publications

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“…This suggests that OSA may promote microvascular pathology that ultimately results in cognitive impairment in the elderly, as previously postulated [ 40 ]. In support of this hypothesis, it has been shown that OSA and nocturnal hypoxaemia are associated with frontal white matter lesions [ 41 , 42 ] and morphometric changes in the deep grey nuclei [ 43 , 44 ]. In addition, it has recently been reported that neurofilament light chain (a marker of white matter integrity) increases in plasma of patients with severe OSA as a function of TST90 after CPAP withdrawal [ 45 ].…”

Section: Discussionmentioning

confidence: 95%

Obstructive sleep apnoea and 5-year cognitive decline in the elderly

et al. 2023

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BackgroundThe relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals.MethodsWe studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined.Results358 elderly individuals without dementia were included (71.0±4.2 years; men 42.5%). A lower mean oxygen saturation during sleep was associated with a steeper decline in Mini-Mental State Examination (B=-0.12, p=0.004), Stroop test condition 1 (B=0.53, p=0.002) and delayed free recall of the Free and Cued Selective Reminding Test (B=-0.05, p=0.008). A longer time spent asleep with an oxygen saturation <90% was associated with a steeper decline in Stroop test condition 1 (B=0.47, p=0.006). Moderation analysis showed that apnoea-hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers.ConclusionsOur results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.

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Section: Discussionmentioning

confidence: 95%

Obstructive sleep apnoea and 5-year cognitive decline in the elderly

et al. 2023

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“…The fact that insomnia is associated with elevated levels of CSF NfL suggest that it may be cleared by the glymphatic system like amyloid ( Xie et al, 2013 ; Albargothy et al, 2018 ) and tau ( Iliff et al, 2014 ). The relationship between NfL and parameters of hypoxemia in OSA patients suggest a different mechanism, potentially via increased oxidative stress and neuroinflammation causing neurodegeneration ( Daulatzai, 2015 ; Snyder et al, 2017 ) and white matter disease ( Rostampour et al, 2020 ; Zacharias et al, 2021 ), which may contribute to sleepiness ( Xiong et al, 2017 ). Although tau-related neurodegeneration of wake-promoting neurons can start in pre-clinical stages of AD ( Braak et al, 2011 ; Stratmann et al, 2016 ), and could contribute to sleepiness ( Oh et al, 2022 ), it is unknown whether it could be associated with higher NfL levels.…”

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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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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“…Non-invasive neuroimaging techniques have been widely used to explore the pathophysiological mechanisms of various diseases, such as neurological and psychiatric disorders. Different neuroimaging techniques have been used to explore related structural, functional, and metabolic alterations in OSA patients ( 7 – 9 ). Many previous studies ( 10 – 13 ) using structural neuroimaging have suggested that OSA patients may have brain tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Aberrant amplitude of low-frequency fluctuations in different frequency bands and changes after one-night positive airway pressure treatment in severe obstructive sleep apnea

et al. 2022

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ObjectiveThis study was aimed to investigate the characteristics of the amplitude of low-frequency fluctuation (ALFF) at specific frequencies in severe obstructive sleep apnea (OSA) patients. A comparison was made between pre-CPAP treatment and one night after continuous positive airway pressure (CPAP) treatment.Methods30 severe OSA patients and 19 healthy controls (HC) were recruited. The ALFF method was used to assess the local features of spontaneous brain activity and calculated at different bands (slow-5 and slow-4). A correlation analysis was performed to evaluate the relationship between the changes of the ALFF and polysomnography data.ResultsCompared with HC, in slow-5 frequency band, OSA patients showed significantly decreased ALFF in the left inferior temporal gyrus, and significantly increased ALFF in the left middle frontal gyrus, left inferior frontal gyrus, triangular part, right superior frontal gyrus, dorsolateral and right middle temporal gyrus. In slow-4 frequency, there was significantly decreased ALFF in the right inferior temporal gyrus, and significantly increased ALFF in the left precuneus, right posterior cingulate gyrus and right median cingulate besides the slow-5 difference band showed. Compared with pre-CPAP, we found that after CPAP treatment, ALFF signals in the left insula in slow-5 and left caudate in slow-4 increased, but the calcarine in slow-4 significantly reduced. Correlation analysis showed that the left angular slow-4 band change was positively correlated with the slow wave sleep change (r = 0.4933, p = 0.0056). The left cerebellum 6 slow-5 band change was positively correlated with the duration of the REM sleep change (r = 0.4563, p = 0.0113), and the left cerebellum 6 slow-4 band change was also positively correlated with the mean blood oxygen change in the REM (r = 0.4591, p = 0.0107) and NREM sleep (r = 0.4492, p = 0.0128).ConclusionWe found that the use of slow-4 was more specific in OSA studies. These results suggested that the severe OSA patients have frequency-related abnormal spontaneous neural activity, which may contribute to a better understanding of the pathological basis of OSA-related diseases and provide a potential therapeutic target for OSA patients.

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Association Between Obstructive Sleep Apnea and Brain White Matter Hyperintensities in a Population-Based Cohort in Germany

Cited by 33 publications

References 43 publications

Obstructive sleep apnoea and 5-year cognitive decline in the elderly

Obstructive sleep apnoea and 5-year cognitive decline in the elderly

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

Aberrant amplitude of low-frequency fluctuations in different frequency bands and changes after one-night positive airway pressure treatment in severe obstructive sleep apnea

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