Decoding the Inter-relationship between Sleep Disorders and Alzheimer’s disease Pathogenesis

2020 ◽  
Vol 19 ◽  
Author(s):  
Zeba Mueed ◽  
Pankaj Kumar Rai ◽  
Mohammad A. Kamal ◽  
Nitesh Kumar Poddar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Sleep Disturbances ◽  
Mammalian Target Of Rapamycin ◽  
Light Therapy ◽  
Paired Helical Filaments ◽  
Bidirectional Relationship ◽  
Causative Agents

Alzheimer’s disease (AD), characterized by abnormally phosphorylated tau, paired helical filaments (PHFs), neurofibrillary tangles (NFTs), deregulated mammalian target of rapamycin (mTOR), Aβ deposits, is a multifactorial disease with sleep disorders being one of the causative agents. Therefore, we have reviewed the literature and have tried to decode the existence of positive feedback, reciprocal and a bidirectional relationship allying between sleep disturbances and AD. Much light has been thrown on the role of tau pathology and amyloid pathology in sleep pathology and its association with AD pathology. We have also discussed the role of melatonin in regulating sleep disorders and AD. The neuroprotective action of melatonin via inhibiting tau hyperphosphorylation and Aβ deposition has also been pondered upon. Moreover, astrocytes involvement in aggravating AD has also been highlighted in this review. Several therapeutic approaches aimed at improving both sleep disorders and AD have been duly discussed such as administration of antidepressants and antihistamines, immunotherapy, metal chelators, melatonin supplementation, light therapy and physical activity. Despite consistent efforts, the complete etiology concerning sleep disorder and AD is still unclear. Therefore, further research is needed to unravel the mechanism involved and also to develop strategies that may help in obstructing AD in its preclinical stage.

scholarly journals Intracerebroventricular streptozotocin‐induced Alzheimer's disease‐like sleep disorders in rats: Role of the GABAergic system in the parabrachial complex

2018 ◽  
Vol 24 (12) ◽  
pp. 1241-1252 ◽  
Author(s):  
Su‐Ying Cui ◽  
Jin‐Zhi Song ◽  
Xiang‐Yu Cui ◽  
Xiao Hu ◽  
Yu‐Nu Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Gabaergic System

Fiat Lux: The Light Became Therapy. An Overview on the Bright Light Therapy in Alzheimer’s Disease Sleep Disorders

2020 ◽  
Vol 77 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Ilaria Roccaro ◽  
Daniela Smirni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Visual Information ◽  
Bright Light ◽  
Light Therapy ◽  
Pharmacological Intervention ◽  
Biological Clocks ◽  
Bright Light Therapy ◽  
Effective Response

Background: A system of photosensitive retinal ganglion cells provides ‘non-visual’ information on the circadian sequences of light to the suprachiasmatic nucleus (SCN), which, as the ‘master clock’, synchronizes the chronobiological mechanisms of all the biological clocks. Damage to SCN structure alters circadian behavioral and hormonal rhythms and interferes with a regular sleep-wake pattern. Several studies have shown that, in aging and in Alzheimer’s disease (AD), circadian rhythms change their synchronization with the environment and behavior loses sync with light. Objective: The current overview aims to examine research studies showing the effect of bright light therapy (BLT) on sleep disorders and sleep-wake patterns in AD. Methods: A literature search was conducted, taking into consideration the relevant studies over the last 20 years. Fifteen studies have been thorough: seven followed an environmental-architectural approach and eight followed a treatment devices approach. Results: Studies agree in considering BLT as a promising non-pharmacological intervention to compensate for circadian rhythm alterations and they support the need for standardized protocols that allow a comparison between multicenter studies. Conclusion: Interestingly, in an attempt to contain the spread of the COVID-19 pandemic, health authorities have forced the population to stay home. Therefore, AD people are not currently able to enjoy exposure to sunlight. It is predictable that they may experience an exacerbation of circadian disturbances and that the BLT can be an effective response to prevent such exacerbation.

Recent Studies on Design and Development of Drugs Against Alzheimer’s Disease (AD) Based on Inhibition of BACE-1 and Other AD-causative Agents

2020 ◽  
Vol 20 (13) ◽  
pp. 1195-1213 ◽  
Author(s):  
Satya P. Gupta ◽  
Vaishali M. Patil
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Protein Misfolding ◽  
Inhibition Mechanism ◽  
Design And Development ◽  
Causative Agents ◽  
Misfolding Disease ◽  
Structural Aspects

Background: Alzheimer’s disease (AD) is one of the neurodegenerative diseases and has been hypothesized to be a protein misfolding disease. In the generation of AD, β-secretase, γ-secretase, and tau protein play an important role. A literature search reflects ever increasing interest in the design and development of anti-AD drugs targeting β-secretase, γ-secretase, and tau protein. Objective: The objective is to explore the structural aspects and role of β-secretase, γ-secretase, and tau protein in AD and the efforts made to exploit them for the design of effective anti-AD drugs. Methods: The manuscript covers the recent studies on design and development of anti-AD drugs exploiting amyloid and cholinergic hypotheses. Results: Based on amyloid and cholinergic hypotheses, effective anti-AD drugs have been searched out in which non-peptidic BACE1 inhibitors have been most prominent. Conclusion: Further exploitation of the structural aspects and the inhibition mechanism for β-secretase, γ-secretase, and tau protein and the use of cholinergic hypothesis may lead still more potent anti-AD drugs.

Melatonin and Sleep Disturbances in Alzheimer’s Disease

2021 ◽  
Vol 20 ◽  
Author(s):  
A. H. M. Safayet Ullah Prodhan ◽  
Cinzia Cavestro ◽  
Mohammad Amjad Kamal ◽  
Md Asiful Islam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disturbances ◽  
Neurodegenerative Disorder ◽  
Bright Light ◽  
Light Therapy ◽  
Reciprocal Relationship ◽  
Exogenous Melatonin ◽  
Melatonin Administration ◽  
Behavioral Memory

: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by sleep, behavioral, memory, and cognitive deteriorations. Sleep disturbance (SD) is a major disease burden in AD which has a reciprocal relationship with AD pathophysiology. It aggravates memory, behavioral, and cognitive complications in AD. Different studies found that melatonin hormone levels reduce even in the pre-clinical stages of AD. Melatonin is the primary sleep-regulating hormone and a potent antioxidant with neuroprotective roles. The decrease in melatonin levels can thus promote SD and AD neuropathology. Exogenous melatonin has the potential to alleviate neuropathology and SD in AD by different mechanisms. Various studies have been conducted so far that assessed the efficacy of exogenous melatonin to treat SD in AD. Though most of the studies suggest that melatonin is useful to ameliorate SD in AD, the remaining studies show opposite results. The timing, dosage, and duration of melatonin administration along with disease condition, genetic, environmental, and some other factors can be responsible for the discrepancies between the studies. More extensive trials with longer durations and higher dosage forms and studies including bright light therapy and melatonin agonists (ramelteon, agomelatine, and tasimelteon) should be performed to determine the efficacy of melatonin to treat SD in AD.

scholarly journals A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

2022 ◽  
Vol 23 (1) ◽  
pp. 504
Author(s):  
Xuemin Peng ◽  
Rongping Fan ◽  
Lei Xie ◽  
Xiaoli Shi ◽  
Kun Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Light Therapy

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

277 Tunable White Light for Elders (TWLITE): A feasibility study of a home-based sleep intervention

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A111-A111
Author(s):  
Carolyn Jones ◽  
Christina Reynolds ◽  
Randall Olson ◽  
Ashten Bontrager ◽  
Sophia Lambert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
General Health ◽  
Short Wavelength ◽  
Sleep Disturbances ◽  
Light Therapy ◽  
Continuous Data ◽  
Lighting System ◽  
Short Wavelength Light ◽  
Wavelength Light

Abstract Introduction Sleep disturbances are common in elderly patients and may contribute to disease progression in certain populations (e.g., Alzheimer’s Disease). Light therapy is a simple and cost-effective intervention to improve sleep. Primary barriers to light therapy are 1) poor acceptability to use of devices and 2) inflexibility of current devices to deliver beyond a fixed spectrum and throughout the entirety of the day. However, dynamic, tunable lighting integrated into the native home lighting system can maximize short-wavelength light in the morning and minimize short-wavelength light in the evening, thus entraining circadian rhythms and treating sleep disturbances, and overcome these limitations. We determined the feasibility of implementing a whole-home tunable lighting system as a potential sleep intervention. Methods Tunable LED lights were installed throughout the homes of healthy older adults already enrolled in an existing study with embedded home assessment platforms (ORCATECH study; n=4 subjects in n=3 homes). In ORCATECH, continuous data on room location, activity, sleep, and general health parameters are collected at minute-to-minute resolution over months to years of participation. This single arm longitudinal design collected participants’ light usage in addition to ORCATECH outcome measures. Primary outcomes for this pilot study included the feasibility and patient acceptability. Exploratory outcomes were sleep metrics (sleep time, latency, efficiency), mobility (room transitions and actigraphy), and overall health indices (weekly body weight, self-report general health questionnaires) both pre- and post-intervention. Results Two subjects terminated the study citing technical difficulties with the lights and a preference for brighter illumination. Of the remaining 2 participants, sleep metrics were explored over a 12-month period spanning pre- and post-installation of lights. Nightly duration in bed was compared with minute-to-minute room entry data and actigraphy with high inter-measure reliability. Conclusion These data support that tunable whole-home lighting systems are reasonably acceptable and feasibly implemented using an automated platform for continuous data collection. Quantification of sleep over long periods of time is robust and reliable in the home environment of elderly subjects. These results will inform implementation of future large-scale lighting intervention studies in patients at risk for developing Alzheimer’s Disease. Support (if any) Hartford Gerontological Center Interprofessional Award, Pacific Northwest National Laboratory, OHSU ORCATECH

scholarly journals Sleep-Based Interventions in Alzheimer’s Disease: Promising Approaches from Prevention to Treatment along the Disease Trajectory

2021 ◽  
Vol 14 (4) ◽  
pp. 383
Author(s):  
Susanna Cordone ◽  
Serena Scarpelli ◽  
Valentina Alfonsi ◽  
Luigi De De Gennaro ◽  
Maurizio Gorgoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Sleep Disturbances ◽  
Early Stage ◽  
Clinical Stage ◽  
Nrem Sleep ◽  
Behavioral Strategies ◽  
Healthy Elderly ◽  
Obstructive Sleep

The multifactorial nature of Alzheimer’s disease (AD) has led scientific researchers to focus on the modifiable and treatable risk factors of AD. Sleep fits into this context, given the bidirectional relationship with AD confirmed by several studies over the last years. Sleep disorders appear at an early stage of AD and continue throughout the entire course of the pathology. Specifically, sleep abnormalities, such as more fragmented sleep, increase in time of awakenings, worsening of sleep quality and primary sleep disorders raise with the severity and progression of AD. Intervening on sleep, therefore, means acting both with prevention strategies in the pre-clinical phase and with treatments during the course of the disease. This review explores sleep disturbances in the different stages of AD, starting from the pre-clinical stage. Particular attention is given to the empirical evidence investigating obstructive sleep apnea (OSA) disorder and the mechanisms overlapping and sharing with AD. Next, we discuss sleep-based intervention strategies in the healthy elderly population, mild cognitive impairment (MCI) and AD patients. We mention interventions related to behavioral strategies, combination therapies, and bright light therapy, leaving extensive space for new and raising evidence on continuous positive air pressure (CPAP) treatment effectiveness. Finally, we clarify the role of NREM sleep across the AD trajectory and consider the most recent studies based on the promising results of NREM sleep enhancement, which use innovative experimental designs and techniques.

scholarly journals The effect of insomnia on development of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Shaghayegh Sadeghmousavi ◽  
Mahsa Eskian ◽  
Farzaneh Rahmani ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Memory Deficits ◽  
Information Recall ◽  
Important Health ◽  
Important Health Issue

Abstract Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

Deciphering Alzheimer’s Disease Pathogenic Pathway: Role of Chronic Brain Hypoperfusion on p-Tau and mTOR

2021 ◽  
Vol 79 (4) ◽  
pp. 1381-1396
Author(s):  
Jack C. de la Torre
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Aging ◽  
Memory Function ◽  
Mammalian Target Of Rapamycin ◽  
Tau Phosphorylation ◽  
Clinical Feature ◽  
Fast Axonal Transport ◽  
Current Topic

This review examines new biomolecular findings that lend support to the hemodynamic role played by chronic brain hypoperfusion (CBH) in driving a pathway to Alzheimer’s disease (AD). CBH is a common clinical feature of AD and the current topic of intense investigation in AD models. CBH is also the basis for the vascular hypothesis of AD which we originally proposed in 1993. New biomolecular findings reveal the interplay of CBH in increasing tau phosphorylation (p-Tau) in the hippocampus and cortex of AD mice, damaging fast axonal transport, increasing signaling of mammalian target of rapamycin (mTOR), impairing learning-memory function, and promoting the formation of neurofibrillary tangles, a neuropathologic hallmark of AD. These pathologic elements have been singularly linked with neurodegeneration and AD but their abnormal, collective participation during brain aging have not been fully examined. The format for this review will provide a consolidated analysis of each pathologic phase contributing to cognitive decline and AD onset, summarized in nine chronological steps. These steps galvanize each factor’s active participation and contribution in constructing a biomolecular pathway to AD onset generated by CBH.

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