Sustained Use of CPAP Slows Deterioration of Cognition, Sleep, and Mood in Patients with Alzheimer's Disease and Obstructive Sleep Apnea: A Preliminary Study

Department of Medicine, University of California, San Diego, CA, USA.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine (Impact Factor: 3.05). 08/2009; 5(4):305-9.
Source: PubMed

ABSTRACT Obstructive sleep apnea (OSA) is common among patients with Alzheimer's disease (AD). Untreated OSA exacerbates the cognitive and functional deficits. Continuous positive airway pressure (CPAP) has recently been shown to have beneficial effects on cognition in AD. Little attention has focused on the long-term benefits of CPAP in these patients.
This was an exploratory study of sustained CPAP use (mean use = 13.3 months, SD = 5.2) among a subset of participants from an initial 6-week randomized clinical trial (RCT) of CPAP in patients with mild to moderate AD. Follow-up included 5 patients who continued CPAP (CPAP+) after completion of the RCT and 5 patients who discontinued CPAP (CPAP-), matched by time of completion of the initial study. A neuropsychological test battery and sleep/mood questionnaires were administered and effect sizes were calculated.
Even with a small sample size, sustained CPAP use resulted in moderate-to-large effect sizes. Compared to the CPAP- group, the CPAP+ group showed less cognitive decline with sustained CPAP use, stabilization of depressive symptoms and daytime somnolence, and significant improvement in subjective sleep quality. Caregivers of the CPAP+ group also reported that their own sleep was better when compared to the final RCT visit and that their patients psychopathological behavior was improved.
The results of this preliminary study raise the possibility that sustained, long-term CPAP treatment for patients with AD and OSA may result in lasting improvements in sleep and mood as well as a slowing of cognitive deterioration. Prospective randomized controlled research trials evaluating these hypotheses are needed.

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Available from: Sonia Ancoli-Israel, Sep 26, 2015
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    • "Sleep interventions at this stage of AD may be difficult to both implement and achieve positive benefits. For example, the incidence of sleep disorders (e.g., sleep apnea) is increased in patients with AD and continuous positive airway pressure (CPAP) therapy may slow or improve cognitive functioning in patients with AD and sleep disordered breathing (SDB) (Ancoli- Israel et al., 2008; Cooke et al., 2009). However, both the diagnosis and treatment of sleep disorders (e.g., SDB) in patients with AD is challenging because of the patients' underlying cognitive dysfunction impeding both the diagnosis via polysomnography and treatment with CPAP. "
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    ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that is a growing public health crisis with a prevalence projected to more than double in the next 20 years. Sleep is frequently impaired in individuals with AD. Further, recent studies have linked numerous age-related sleep disturbances such as poor sleep efficiency and sleep apnea, to future risk of cognitive impairment. Aggregation of amyloid-β (Aβ) into extracellular plaques in the brain is a key step in AD pathogenesis and likely begins 20 years before the onset of dementia. Aβ concentrations in both humans and mouse models show Aβ concentrations rise during wakefulness and fall during sleep, that is, an Aβ diurnal pattern. There is evidence in animal models that changes in sleep time alter Aβ deposition, suggesting that sleep may play a role in AD pathogenesis. A hypothetical model for the role of sleep and the Aβ diurnal pattern in AD pathogenesis is proposed.
    Neurobiology of Aging 05/2014; 35. DOI:10.1016/j.neurobiolaging.2014.03.035 · 5.01 Impact Factor
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    • "The most effective treatment of OSA is continuous positive airway pressure (CPAP). In a 6-week randomized placebo controlled clinical trial of CPAP in patients with mild-moderate AD and OSA, CPAP improved OSA, objective sleep parameters , and daytime sleepiness and resulted in modest improvements in measures of cognitive functioning [146] [147] [148] [149]. "
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    ABSTRACT: Different kinds of challenge can alter cognitive process and electroencephalographic (EEG) rhythms in humans, thus providing paradigms to evaluate treatment effects in drug discovery. Here, we report recent findings on the effects of challenges represented by sleep deprivation (SD), transient hypoxia, and transcranial magnetic stimulation (TMS) in healthy volunteers on cognitive processes and EEG rhythms to build a knowledge platform for novel research for drug discovery in AD Alzheimer's disease (AD). Sleep pressure enhanced frontal delta rhythms (< 4 Hz) during the night, while SD increased slow rhythms in the theta range (4-7 Hz), and reduced resting state alpha rhythms (8-12 Hz) during the day after. Furthermore, SD transiently affected cognitive performance. On the other hand, transient experimental hypoxia induced abnormal posterior resting state delta and alpha rhythms in healthy volunteers that resemble the abnormal EEG rhythms typically recorded in AD patients. However, the relationship between the cognitive and EEG effects of such challenge is poorly understood. In the same line, TMS reversibly interfered with higher brain functions during EEG recordings, but few studies investigated the relationship between the cognitive and EEG effects of its interfering effects. In conclusion, SD is the most mature challenge model for testing new drugs for AD symptoms. Future investigations are welcome to better understand the opportunities offered by TMS and hypoxia challenges.
    Current Alzheimer research 03/2014; 11(5). DOI:10.2174/1567205011666140317095623 · 3.89 Impact Factor
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    • "Treatment for OSA, such as continuous airway pressure (CPAP), has been shown to decrease sleep disturbance in patients with AD and OSA [14] and, although the cognitive benefits of CPAP are not yet clear, some studies have shown positive improvement in neuropsychological functioning [7, 15]. Overall, there is evidence suggesting that, even in established dementia, there may be merit in addressing this problem and this may be even greater if intervention targeted critical “at risk” periods such as MCI. "
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    ABSTRACT: Purpose. Mild cognitive impairment (MCI) is considered an "at risk" state for dementia and efforts are needed to target modifiable risk factors, of which Obstructive sleep apnoea (OSA) is one. This study aims to evaluate the predictive utility of the multivariate apnoea prediction index (MAPI), a patient self-report survey, to assess OSA in MCI. Methods. Thirty-seven participants with MCI and 37 age-matched controls completed the MAPI and underwent polysomnography (PSG). Correlations were used to compare the MAPI and PSG measures including oxygen desaturation index and apnoea-hypopnoea index (AHI). Receiver-operating characteristics (ROC) curve analyses were performed using various cut-off scores for apnoea severity. Results. In controls, there was a significant moderate correlation between higher MAPI scores and more severe apnoea (AHI: r = 0.47, P = 0.017). However, this relationship was not significant in the MCI sample. ROC curve analysis indicated much lower area under the curve (AUC) in the MCI sample compared to the controls across all AHI severity cut-off scores. Conclusions. In older people, the MAPI moderately correlates with AHI severity but only in those who are cognitively intact. Development of further screening tools is required in order to accurately screen for OSA in MCI.
    01/2014; 2014:945287. DOI:10.1155/2014/945287
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