Alzheimer's disease and sleep disturbances: a review

Borges, Conrado Regis; Poyares, Dalva; Piovezan, Ronaldo D.; Nitrini, Ricardo

doi:10.1590/0004-282x20190149

Cited by 46 publications

(19 citation statements)

References 61 publications

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“…Furthermore, this region is a known epileptogenic zone (33). Our experiments highlight the importance of the cingulate cortex and the consequences of its vulnerability in early AD at the cell-, network- and behavior level (34, 35).…”

Section: Discussionmentioning

confidence: 80%

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Shah

Gsell

Wahis

et al. 2022

Preprint

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Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex, several years before amyloid deposition. We found the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astroglial calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral hyperactivity. In conclusion, we show for the first time that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.

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Section: Discussionmentioning

confidence: 80%

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Shah

Gsell

Wahis

et al. 2022

Preprint

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“…Sleep disturbances are common in Alzheimer's disease, in elderly people and in depression [96][97][98][99]. There is no convincing evidence that sleep disturbances cause Alzheimer's disease.…”

Section: Depression Sleep and Alzheimer's Diseasementioning

confidence: 99%

Probable Causes of Alzheimer’s Disease

Adams¹

2021

Sci

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A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

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“…Even with "normal" aging mechanisms, PSG reveals a decrease in slow-wave sleep (SWS), delta-power, sleep efficiency (SE), and an increase in comorbid sleep disorders such as sleep-disordered breathing and periodic limb movements of sleep [17]. The added alterations of neuronal structure in AD can further exacerbate sleep disruption, resulting in an amplified worsening of sleep parameters already seen in aging [18]. Behavioral observations of sleep in an AD special care unit observed that this worsening of sleep was associated with the severity of dementia [19].…”

Section: Overviewmentioning

confidence: 99%

Impact of Pharmacotherapy on Insomnia in Patients with Alzheimer’s Disease

Roland

Bliwise

2021

Drugs Aging

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Insomnia is a pervasive sleep disorder affecting numerous patients across diverse demographical populations and comorbid disease states. Contributing factors are often a complex interaction of biological, psychological, and social components, requiring a multifaceted approach in terms of both diagnosis and management. In the setting of Alzheimer's disease, insomnia is an even more complicated issue, with a higher overall prevalence than in the general population, greater complexity of contributing etiologies, and differences in diagnosis (at times based on caregiver observation of sleep disruption rather than subjective complaints by the individual with the disorder), and requiring more discretion in terms of treatment, particularly in regard to adverse effect profile concerns. There also is growing evidence of the bidirectional nature of sleep disruption and Alzheimer's disease, with insomnia potentially contributing to disease progression, making the condition even more paramount to address. The objective of this review was to provide the clinician with an overview of treatment strategies that may have value in the treatment of disturbed sleep in Alzheimer's disease. Nonpharmacological approaches to treatment should be exhausted foremost; however, pharmacotherapy may be needed in certain clinical scenarios, which can be a challenge for clinicians given the paucity of evidence and guidelines for treatment in the subpopulation of Alzheimer's disease. Agents such as sedating antidepressants, melatonin, and site-specific γ-aminobutyric acid agonists are often employed based on historical usage but are not necessarily supported by high-quality trials. Newer agents such as dual orexin receptor antagonists have demonstrated some promise but still need further evaluation.

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Alzheimer's disease and sleep disturbances: a review

Cited by 46 publications

References 61 publications

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s Disease

Probable Causes of Alzheimer’s Disease

Impact of Pharmacotherapy on Insomnia in Patients with Alzheimer’s Disease

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