Candidate mechanisms linking insomnia disorder to Alzheimer’s disease risk

Chappel‐Farley, Miranda G.; Lui, Kitty; Dave, Abhishek; Chen, Ivy Y.; Mander, Bryce A.

doi:10.1016/j.cobeha.2020.01.010

Cited by 8 publications

(8 citation statements)

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“…These cognitive domains are believed to be impaired early, and the DMN is the first dysfunctional network affected by increased beta-amyloid deposition in patients with AD ( 1 , 20 ) as well as in patients with SLD ( 32 , 33 ). The abnormal DMN, especially the overactivated hippocampus and medial temporal lobe, is reported to associate with dysfunction of emotion ( 34 ), memory, and cognition in patients with SLD ( 15 , 35 ) and could also interact with increased beta-amyloid production and greater local deposition ( 1 ) and facilitate the following hypo-activation and atrophy of hippocampus and other DMN regions in patients with AD ( 8 ). However, whether overactivation ( 8 , 15 ), hypo-activation ( 26 , 29 ), or no change ( 22 , 27 ) of the hippocampus in the different developmental processes of these two diseases is still controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers even believe that SLD has decisive effects on AD ( 2 ). It is reported that roughly more than 50% of patients with AD have got significant SLD ( 8 ), which may include insomnia, obstructive apnea hypopnea syndrome (OSA), rapid eye movement sleep behavior disorder (RBD), sleep apnea, shortened sleep duration, fragmented sleep, slow wave sleep disruption, and misalignment of circadian rhythm ( 9 ). Older adults with SLD are more likely to have a diagnosis of AD or cognitive decline ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, patients with SLD show decreased brain functional and structural indices in the frontal cortex, temporal gyrus, fusiform gyrus, striatum, cingulate cortex, precentral gyrus, and reduced glucose metabolism in the limbic system as well as increased brain activation and regional homogeneity in the middle frontal gyrus, precunus, cingulate gyrus ( 21 ) and overactivation in the hypothalamic-pituitary-adrenal cascade ( 5 ). However, one review indicates that cortical hyperarousal other than hypo-arousal activities, as the central feature of SLD, may be located at the temporal cortex and hippocampus and could contribute to both AD and SLD pathogenesis so as to increase their comorbidity rate ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review

2021

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Introduction: Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions.Methods: A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases.Results: Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD.Conclusions: Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review

2021

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“…This means conducting larger scale studies that can implement the ATN framework to understand how the presence and absence and relative burdens of different AD pathologies at different AD stages may impact local sleep. This will also require examining other mechanisms, including metabolic dysfunction, chronic inflammation, and HPA-axis dysregulation, all of which contribute to AD pathophysiology and are related to sleep disturbance ( Heppner et al, 2015 ; Spangenberg and Green, 2017 ; Caruso et al, 2018 ; Carroll and Macauley, 2019 ; Irwin and Vitiello, 2019 ; Chappel-Farley et al, 2020 ). Chronic inflammation, in particular, is a promising target for future research, because of its known independent interactions with sleep expression and multiple aspects of AD pathophysiology, as well as the paucity of data addressing its links with age-related deficits in local sleep expression.…”

Section: Discussionmentioning

confidence: 99%

Local Sleep and Alzheimer’s Disease Pathophysiology

Mander

2020

Front. Neurosci.

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Even prior to the onset of the prodromal stages of Alzheimer's disease (AD), a constellation of sleep disturbances are apparent. A series of epidemiological studies indicate that multiple forms of these sleep disturbances are associated with increased risk for developing mild cognitive impairment (MCI) and AD, even triggering disease onset at an earlier age. Through the combination of causal manipulation studies in humans and rodents, as well as targeted examination of sleep disturbance with respect to AD biomarkers, mechanisms linking sleep disturbance to AD are beginning to emerge. In this review, we explore recent evidence linking local deficits in brain oscillatory function during sleep with local AD pathological burden and circuit-level dysfunction and degeneration. In short, three deficits in the local expression of sleep oscillations have been identified in relation to AD pathophysiology: (1) frequencyspecific frontal deficits in slow wave expression during non-rapid eye movement (NREM) sleep, (2) deficits in parietal sleep spindle expression, and (3) deficits in the quality of electroencephalographic (EEG) desynchrony characteristic of REM sleep. These deficits are noteworthy since they differ from that seen in normal aging, indicating the potential presence of an abnormal aging process. How each of these are associated with β-amyloid (Aβ) and tau pathology, as well as neurodegeneration of circuits sensitive to AD pathophysiology, are examined in the present review, with a focus on the role of dysfunction within fronto-hippocampal and subcortical sleep-wake circuits. It is hypothesized that each of these local sleep deficits arise from distinct networkspecific dysfunctions driven by regionally-specific accumulation of AD pathologies, as well as their associated neurodegeneration. Overall, the evolution of these local sleep deficits offer unique windows into the circuit-specific progression of distinct AD pathophysiological processes prior to AD onset, as well as their impact on brain function. This includes the potential erosion of sleep-dependent memory mechanisms, which may contribute to memory decline in AD. This review closes with a discussion of the remaining critical knowledge gaps and implications of this work for future mechanistic studies and studies implementing sleep-based treatment interventions.

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“…Based on these similarities between the pathophysiology of insomnia and mechanisms that cause AD including accumulation of Aβ, inflammation, and other components which are discussed in this review, insomnia disorder can be linked to AD risk [420][421][422] and this could be a novel target for treatments or prevention AD development and/or resolve the cognitive decline in patients with AD in the future [423].…”

Section: Discussionmentioning

confidence: 99%

The effect of insomnia on development of Alzheimer’s disease

Sadeghmousavi

Eskian

Rahmani

et al. 2020

J Neuroinflammation

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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.

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Candidate mechanisms linking insomnia disorder to Alzheimer’s disease risk

Cited by 8 publications

References 65 publications

Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review

Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review

Local Sleep and Alzheimer’s Disease Pathophysiology

The effect of insomnia on development of Alzheimer’s disease

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