Link between sleep, cognitive impairment in the elderly

Daytime sleepiness is very common in the elderly with prevalence rates of up to 50 percent. Caused by sleep-disordered breathing (SDB), a disruption of normal breathing during sleep, these cause recurrent awakenings and subsequent excessive daytime sleepiness.

In an editorial in the current issue of Neurology, a Boston University School of Medicine (BUSM) researcher stresses that it is now time for physicians to consider the association between these sleep conditions and cognitive impairment in the elderly.

In the same issue of the journal, researchers of the “HypnoLaus Study” investigated an older population (over the age of 65), with and without cognitive impairment. They performed sleep studies on these groups and found that the group with cognitive impairments had more sleep disturbances attributed to SDB.

“Although this does not necessarily mean that sleep apnea causes cognitive impairment in the elderly, it does highlight the association,” explained corresponding author Sanford Auerbach, MD, associate professor of neurology and psychiatry at BUSM and director of the Sleep Disorders Center at Boston Medical Center.

According to Auerbach the causal link between SDB /obstructive sleep apnea (OSA) and cognitive impairment in the elderly is not entirely clear. “Nevertheless, it does raise the issue that clinicians evaluating OSA in the elderly should screen for cognitive impairments. Furthermore, clinicians evaluating cognitive impairment in the elderly should also screen their patients for sleep disturbance and OSA.”

Even though it is not clear that treatment of OSA will delay or prevent the cognitive impairment and possible development of dementia, Auerbach believes that treatment of OSA will certainly improve the quality of life for these patients.

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Materials provided by Boston University Medical Center. Note: Content may be edited for style and length.

 

Evidence insufficient regarding screening for obstructive sleep apnea

The U.S. Preventive Services Task Force (USPSTF) has concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for obstructive sleep apnea in asymptomatic adults (including adults with unrecognized symptoms). The report appears in the January 24/31 issue of JAMA.

This is an I statement, indicating that evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Based on data from the 1990s, the estimated prevalence of obstructive sleep apnea (OSA) in the United States is 10 percent for mild OSA and 3.8 percent to 6.5 percent for moderate to severe OSA. Current prevalence may be higher, given the increasing prevalence of obesity. Severe OSA is associated with an increased risk of death, cardiovascular disease and cerebrovascular events, diabetes, cognitive impairment, decreased quality of life and motor vehicle crashes. The proportion of persons with OSA who are asymptomatic or have unrecognized symptoms is unknown. To issue a new recommendation on screening for OSA, the USPSTF reviewed the evidence on the accuracy, benefits and potential harms of screening for OSA in asymptomatic adults seen in primary care, including those with unrecognized symptoms. The USPSTF also evaluated the evidence on the benefits and harms of treatment of OSA on intermediate and final health outcomes.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Detection

Evidence on the use of validated screening questionnaires in asymptomatic adults (or adults with unrecognized symptoms) to accurately identify who will benefit from further testing for OSA is inadequate. The USPSTF identified this as a critical gap in the evidence.

Benefits of Early Detection and Intervention or Treatment

The USPSTF found inadequate direct evidence on the benefit of screening for OSA in asymptomatic populations. The USPSTF found no studies that evaluated the effect of screening for OSA on health outcomes. The USPSTF found at least adequate evidence that treatment with continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) can improve intermediate outcomes (e.g., the apnea-hypopnea index, Epworth Sleepiness Scale score, and blood pressure) in populations referred for treatment. However, the applicability of this evidence to screen-detected populations is limited.

The USPSTF found evidence that treatment with CPAP can improve general and sleep-related quality of life in populations referred for treatment, but the applicability of this evidence to screen-detected populations is unknown.

The USPSTF found inadequate evidence on whether treatment with CPAP or MADs improves other health outcomes (mortality, cognitive impairment, motor vehicle crashes, and cardiovascular or cerebrovascular events). The USPSTF also found inadequate evidence on the effect of treatment with various surgical procedures in improving intermediate or health outcomes.

Harms of Early Detection and Intervention or Treatment

The USPSTF found inadequate evidence on the direct harms of screening for OSA. The USPSTF found adequate evidence that the harms of treatment of OSA with CPAP and MADs are small. The USPSTF found inadequate evidence on the harms of surgical treatment of OSA.

Summary

The USPSTF found insufficient evidence on screening for or treatment of OSA in asymptomatic adults or adults with unrecognized symptoms. Therefore, the USPSTF was unable to determine the magnitude of the benefits or harms of screening for OSA or whether there is a net benefit or harm to screening.

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Regulating gasotransmitters could improve care for sleep apnea

Unbalanced signaling by two molecules that regulate breathing leads to sleep apnea in mice and rats, researchers report in the Jan. 23, 2017, Proceedings of the National Academy of Sciences. They show, working with rodents, that injection of a substance that reduces production of one of those signals, hydrogen sulfide, can prevent apneas. This approach has the potential to help people suffering from multiple forms of sleep-disordered breathing.

Apnea, the periodic cessation of breathing during sleep, is a major health problem. It affects more than 10 million people in the United States, often disrupting their sleep hundreds of times each night. This profoundly fragmented sleep causes daytime drowsiness, curtails academic achievement and professional productivity, and is a common cause of motor-vehicle or on-the-job accidents. It can also lead to life-threatening health issues, including hypertension and stroke.

Current apnea treatments, such as the use of continuous positive airway pressure (C-PAP) while sleeping, are difficult for many patients to maintain and provide only limited benefits.

“We believe we have found an approach that could significantly improve the clinical management of sleep apneas by restoring the balance between two key gasotransmitters in the blood — carbon monoxide and hydrogen sulfide,” said Nanduri Prabhakar, PhD, the Harold Hines Jr. Professor of Medicine and Director of the Institute for Integrative Physiology and Center for Systems Biology of O2 at the University of Chicago.

Prabhakar and colleagues from the University of Chicago, the Illinois Institute of Technology, Beth Israel Deaconess Medical Center (Boston), and Johns Hopkins University (Baltimore), focused on the carotid bodies, a tiny cluster of cells embedded in the left and right carotid arteries, which pass through the neck.

The carotid bodies are the primary organ for sensing oxygen and carbon dioxide levels in arterial blood. Glomus cells in the carotid bodies produce the enzymes heme oxygenase 2 (HO-2), which generates carbon monoxide (CO) when oxygen levels are appropriate, and cystathionine-γ-lyase (CSE), which generates hydrogen sulfide (H2S) when oxygen levels dip.

During normal breathing during sleep, CO prevents the production of H2S by inhibiting CSE. When apnea begins and oxygen levels drop, however, CSE produces H2S, which stimulates the carotid bodies to increase breathing, heart rate and blood pressure. This leads to a sudden awakening.

Prabhakar and colleagues tested two ways to manipulate this system by modulating the enzymes, CSE and HO-2, involved in CB signaling. When they gave a CSE inhibitor, L-propargyl glycine (L-PAG) by injection or by mouth to mice lacking HO-2 or rats predisposed to heightened CB activity, it reduced the frequency of apnea, underscoring the role of H2S in triggering apnea.

The response to L-PAG was “rapid, reversible, and did not result in overt toxicity within the dose range tested,” the investigators wrote. Conversely, administering CORM3, a compound that releases carbon monoxide gas, to HO-2 deficient mice, restored normal breathing within 10 minutes. Notably, L-PAG reduced the number of both obstructive and central apneas in a dose-dependent and reversible manner.

The findings “demonstrate the salutary effects of blocking CSE during apnea and point to a potential therapeutic strategy for human sleep apnea,” according to the authors. “Our results suggest that pharmacologic targeting of the CB with a CSE inhibitor, such as L-PAG, might prevent apneas.”

These observations “provide proof-of-concept for the therapeutic potential of CSE inhibitors,” the authors wrote, but the doses of L-PAG required to normalize breathing were relatively high. More studies are needed to develop and test more potent CSE inhibitors.

“Nonetheless,” they conclude, “pharmacologic modulation of the CB chemoreflex by an inhibitor of H2S synthesis, as shown in the present study, has the potential to significantly improve the clinical management of sleep apnea.”