Abstract
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.
Highlights
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 sleep disorder (SLD)
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). These findings show some shared and bidirectional interactions of brain disturbances, neurodegeneration, and neuropathology between AD and SLD (9), the key brain changes associated with high comorbidity and their interactions are still controversial and remain to be elucidated
The present review provides an overview of the specific neuroimaging findings of patients with comorbid AD and SLD, their limitations, and future research directions
Summary
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. 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. Finding possible risk or comorbid factors and effective intervention of this disease is warranted. As one of the most important noxious factors on physical and mental health (4), sleep disorder (SLD) is reported to be closely associated with development of AD (5–7). RBD may lead to cognitive impairment and pathologies of AD (12)
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