Sleep disorders and Alzheimer’s disease pathophysiology: The role of the Glymphatic System. A scoping review

Astara, Kyriaki; Tsimpolis, Alexandros; Kalafatakis, Konstantinos; Vavougios, George D.; Xiromerisiou, Georgia; Dardiotis, Efthimios; Christodoulou, Nikos G.; Samara, Myrto T.; Lappas, Andreas S.

doi:10.1016/j.mad.2023.111899

Cited by 5 publications

(5 citation statements)

References 137 publications

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“…Interestingly, significantly reduced DTI-ALPS parameters have been detected both in PD patients and in those with prodromal stages, such as REM sleep behavior disorder (RBD), suggesting an early disruption in the glymphatic activity [31,32]. Additionally, the results from a data-driven analysis of 70 studies support the notion of an interrelationship between sleep disorders and AD pathogenesis, mediated by the glymphatic system [13]. It is well documented that in AD patients, untreated sleep disorders are strongly associated with accelerated cognitive decline and phenoconversion to a major neurocognitive disorder [33].…”

Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 83%

“…Indeed, human studies revealed that sleep is associated with greater glymphatic activity, as compared with wakefulness [2]. This occurs since sleep constitutes an optimal "spatiotemporal" environment for glymphatic clearance [13]. The term "spatial" refers to the interstitial space, in which CSF-ISF exchanges, a phenomenon enlarged by 60% during sleep [14].…”

Section: The Second Question: Factors Influencing/modulating the Glym...mentioning

confidence: 99%

“…Taken together, these findings support the strict relationship between altered MRI functional and structural parameters reflecting an impairment in the glymphatic system and the AD disease severity. Taking a step further to define "glymphatic" neurodegeneration, sleep has been now recognized as a fundamental functional element of the glymphatic system that highlights its state dependency [13]. Supporting this, sleep disorders, including poor sleep quality, sleep deprivation, sleep fragmentation and obstructive sleep apnea (OSA), are not only very common in PD and AD but have also been recently linked to impaired glymphatic function [29,30].…”

Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 99%

“…It is well documented that in AD patients, untreated sleep disorders are strongly associated with accelerated cognitive decline and phenoconversion to a major neurocognitive disorder [33]. This is the case of OSA, leading to an elevated intrathoracic and intracranial pressure that can cause increased venous pressure and impedance in the outflow compartment of the glymphatic system [13]. An enlargement of the perivascular space in the bilateral frontal cortex, the basal ganglia, bilateral lateral ventricles and the fourth ventricle has been detected in OSA patients, in association with the severity and the existence of hypoxemia [34].…”

Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 99%

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“Glymphatic” Neurodegeneration: Is Sleep the Missing Key?

Ferini-Strambi,

Salsone

2024

CTN

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Robust evidence suggests that the glymphatic system plays a key role in preserving brain health. Indeed, its activity in maintaining homeostasis by clearing neurotoxic proteins such as beta-amyloid from the human brain is essential. Sleep represents the factor that mainly influences this system, since it is selectively active during the night, in particular during non-rapid eye movement (NREM) sleep. This is true, since the sleep head position, in particular the supine position for its relationship to the status of opening/closing of the jugular veins, appears to be determinant for the development of future neurodegeneration. Growing evidence from human and animal models highlights the neurobiological link between sleep, glymphatic dysfunction and neurodegeneration. On the other hand, several modifiable factors have been recently identified modulating (improve/reduce) glymphatic system activity, such as Omega-3 polyunsaturated fatty acids, stress, hypertension, physical activity, alcohol, gender and genetic predisposition, in particular variants of aquaporin-4 (AQP4). From this viewpoint, our ambition is to discuss how the glymphatic system works in the brain, what factors mainly impact on this activity and its strict relation with the neurodegeneration. Future directions might include the analysis of factors modulating glymphatic system activity and a personalized glymphatic profile, “glymphatom”, as a natural target for preventive neurodegenerative treatment.

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Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 83%

Section: The Second Question: Factors Influencing/modulating the Glym...mentioning

confidence: 99%

Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 99%

Section: The Third Question: "Glymphatic" Neurodegeneration and Sleepmentioning

confidence: 99%

See 2 more Smart Citations

“Glymphatic” Neurodegeneration: Is Sleep the Missing Key?

Ferini-Strambi,

Salsone

2024

CTN

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“…It has been demonstrated that this function is active only during sleep, particularly during slow-wave sleep. This may represent an additional mechanism by which sleep fragmentation, characteristic of OSA, may contribute to cognitive decline and the pathogenesis of Alzheimer's disease [41][42][43].…”

Section: Neuroinflammationmentioning

confidence: 99%

The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration

Mitroshina,

Vedunova

2024

IJMS

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Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer’s disease (AD) and Parkinson’s disease (PD) represent the most prevalent forms of neurodegeneration. To date, a substantial body of experimental evidence has strongly implicated hypoxia in the pathogenesis of numerous neurological disorders, including AD, PD, and other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) is a transcription factor that triggers a cell survival program in conditions of oxygen deprivation. The involvement of HIF-1α in neurodegenerative processes presents a complex and sometimes contradictory picture. This review aims to elucidate the current understanding of the interplay between hypoxia and the development of AD and PD, assess the involvement of HIF-1 in their pathogenesis, and summarize promising therapeutic approaches centered on modulating the activity of the HIF-1 complex.

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