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      Respiratory Dysfunction in Alzheimer’s Disease—Consequence or Underlying Cause? Applying Animal Models to the Study of Respiratory Malfunctions

      , , ,
      International Journal of Molecular Sciences
      MDPI AG

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          Abstract

          Alzheimer’s disease (AD) is a neurodegenerative brain disease that is the most common cause of dementia among the elderly. In addition to dementia, which is the loss of cognitive function, including thinking, remembering, and reasoning, and behavioral abilities, AD patients also experience respiratory disturbances. The most common respiratory problems observed in AD patients are pneumonia, shortness of breath, respiratory muscle weakness, and obstructive sleep apnea (OSA). The latter is considered an outcome of Alzheimer’s disease and is suggested to be a causative factor. While this narrative review addresses the bidirectional relationship between obstructive sleep apnea and Alzheimer’s disease and reports on existing studies describing the most common respiratory disorders found in patients with Alzheimer’s disease, its main purpose is to review all currently available studies using animal models of Alzheimer’s disease to study respiratory impairments. These studies on animal models of AD are few in number but are crucial for establishing mechanisms, causation, implementing potential therapies for respiratory disorders, and ultimately applying these findings to clinical practice. This review summarizes what is already known in the context of research on respiratory disorders in animal models, while pointing out directions for future research.

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          Most cited references179

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          Alzheimer's disease: the amyloid cascade hypothesis

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            Inflammation as a central mechanism in Alzheimer's disease

            Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain's resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed coverage of a number of microglia-related signaling mechanisms that have been implicated in AD. Additional information on microglia signaling and a number of cytokines in AD are also reviewed. We also review the potential connection of risk factors for AD and how they may be related to inflammatory mechanisms.
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              Increased prevalence of sleep-disordered breathing in adults.

              Sleep-disordered breathing is a common disorder with a range of harmful sequelae. Obesity is a strong causal factor for sleep-disordered breathing, and because of the ongoing obesity epidemic, previous estimates of sleep-disordered breathing prevalence require updating. We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988-1994 and 2007-2010 using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study that was established in 1988 with participants randomly selected from an employed population of Wisconsin adults. A total of 1,520 participants who were 30-70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing. Participants were invited for repeat studies at 4-year intervals. The prevalence of sleep-disordered breathing was modeled as a function of age, sex, and body mass index, and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey. The current prevalence estimates of moderate to severe sleep-disordered breathing (apnea-hypopnea index, measured as events/hour, ≥15) are 10% (95% confidence interval (CI): 7, 12) among 30-49-year-old men; 17% (95% CI: 15, 21) among 50-70-year-old men; 3% (95% CI: 2, 4) among 30-49-year-old women; and 9% (95% CI: 7, 11) among 50-70 year-old women. These estimated prevalence rates represent substantial increases over the last 2 decades (relative increases of between 14% and 55% depending on the subgroup).
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                Author and article information

                Contributors
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                Journal
                IJMCFK
                International Journal of Molecular Sciences
                IJMS
                MDPI AG
                1422-0067
                February 2024
                February 16 2024
                : 25
                : 4
                : 2327
                Article
                10.3390/ijms25042327
                38397004
                3ad9264e-bbbc-4adf-893e-bca1d7075bcb
                © 2024

                https://creativecommons.org/licenses/by/4.0/

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