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- Cedernaes, Jonathan, et al.
(författare)
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Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease
- 2017
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Ingår i: Sleep Medicine Reviews. - : Saunders Elsevier. - 1087-0792 .- 1532-2955. ; 31, s. 102-111
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Forskningsöversikt (refereegranskat)abstract
- During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.
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| 2. |
- Sharma, Ram A, et al.
(författare)
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Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study.
- 2018
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 197:7, s. 933-943
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood.To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly.Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 to 90, were non-depressed and had a consensus clinical diagnosis of cognitively normal. CSF Amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B Positron Emission Tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device.We found that severity of OSA indices (lnAHIall [F1,88=4.26, p<.05] and lnAHI4% [F1,87=4.36, p<.05]) were associated with annual rate of change of CSF Aβ42 using linear regression after adjusting for age, sex, BMI and ApoE4 status. LnAHIall and lnAHI4 were not associated with increases in ADPiB-mask most likely due to the small sample size although there was a trend for lnAHIall (F1,28=2.96, p=.09 and F1,28=2.32, n.s. respectively).In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2 year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.
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