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Sleep-Disordered Breathing Is Associated with Brain Changes in Cognitively Unimpaired Adults

Article In Brief

Sleep-disordered breathing among older adults who were not cognitively impaired contributed to changes in Alzheimer disease-sensitive brain regions.

Sleep disordered breathing (SDB) resulting in fragmented sleep and hypoxia appears to be associated with brain changes in cognitively unimpaired older adults that may put them at risk for cognitive decline, and Alzheimer's Disease (AD), according to a March 23 online report in JAMA Neurology.

The results from a cross-sectional study of more than 100 healthy older adults (average age 69) support screening of cognitively asymptomatic older populations for SDB, said the lead author Geraldine Rauchs, PhD, of the Medit-Ageing Research Group, in Caen, France, and colleagues.

Dr. Rauchs told Neurology Today it is probably not feasible to screen all older people. “However, if patients complain of poorly restorative sleep, daytime sleepiness and/or attention deficits, then it is important to screen them for SDB,” she said. There is an efficient treatment using continuous positive airway pressure (CPAP) and treating SDB may help to reduce the risk of cognitive decline and dementia. It will also improves quality of life.”

Dr. Rauchs said preventative information strategies can be designed for informing patients about sleep disturbance and negative consequences for the brain. She added there is a common stereotype that SDB only affects sedentary and overweight men. That cohort is at higher risk of SDB, she said, but her study and others are showing that the risk is not confined to obese or sedentary men.

Dr. Rauchs said physician colleagues who see patients with SDB regularly inform the research group about the risk associated with untreated SDB, especially the risk of cardiovascular disease. “They also explain that SDB can result in cognitive deficits, mainly [in] attention and sometimes memory,” she said. “There is a growing media coverage of this subject, so I think people are rapidly becoming aware that preserving sleep quality and treating sleep troubles is an important factor in aging well.”

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“I was struck by how common obstructive sleep apnea is in this cohort. I do think it is important to look for sleep disorders among otherwise healthy older people because they are exceedingly common. Most sleep disorders are undiagnosed, particularly among people who do not have access to a subspecialist, and many people dont realize they have a sleep disorder.”—DR. YO-EL JU

Study Design, Findings

To study the issue, Dr. Rauchs and colleagues enrolled 127 community-dwelling older adults who were deemed to be cognitively asymptomatic during a baseline visit as part of the Age-Well randomized clinical trial. The trial is conducted by the Medit-Ageing European Project25 and sponsored by the French National Institute of Health and Medical Research (INSERM). Participants underwent a neuropsychological evaluation including tests of global cognitive functioning, processing speed, attention, working memory, executive functions, and episodic memory.

They also received at-home polysomnography measuring sleep apnea and sleep hypopnea. Approximately 75 percent of the participants had varying degrees of sleep apnea. Based on the apnea-hypopnea index (AHI) value, participants were classified into two groups: 31 individuals without SDB (AHI< 15 events per hour) and 96 individuals with SDB (AHI ≥ 15 events per hour). Importantly, there was no association with cognitive performance, self-reported cognitive or sleep difficulties, or excessive daytime sleepiness.

Both groups underwent structural MRI, two types of PET, and genotyping for apolipoprotein E4.

Participants with SDB had greater amyloid burden in the left precuneus, posterior cingulate, calcarine, and cuneus, than those without SDB. They also showed greater gray matter (GM) volume in the precuneus and posterior cingulate cortex, bilaterally, and greater perfusion in parietooccipital regions. In addition, participants with SDB had greater glucose metabolism in the precuneus and posterior cingulate cortex; disruptions of connectivity in that region of the brain are believed to play a role in the development of AD, the study authors pointed out. Finally, the study authors reported that greater amyloid burden was associated with the severity of hypoxia.

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalized with greater GM volume, perfusion, and metabolism in older participants with SDB who are cognitively unimpaired,” they wrote. “We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms.”

Expert Commentary

Sleep experts who reviewed the study for Neurology Today agreed that the findings confirm previous research and break new ground in understanding the association between sleep and cognitive decline or AD.

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“In light of the current US Preventive Services Task Force (USPSTF 2017) conclusion that there was insufficient evidence to support screening for sleep apnea in asymptomatic individuals, I think this study provides additional evidence in support for screening at least in an older age group.”—DR. PHYLLIS C. ZEE

“The study employs a multimodal imaging approach to assess structural and functional changes in AD-relevant brain regions in cognitively unimpaired older adults with sleep-disordered breathing and is the largest and most comprehensive imaging study to date of brain changes and polysomnographic parameters in `asymptomatic' SDB,” said Phyllis C. Zee, MD, PhD, chief of sleep medicine in the department of neurology at Feinberg School of Medicine of Northwestern Medicine.

“The study is sufficiently powered to demonstrate greater amyloid deposition and co-localization of increased neuronal activity in AD relevant brain regions,” Dr. Zee said. “Furthermore, the results indicate that in addition to the severity of SDB as measured by the number of respiratory events, the overall hypoxia burden during sleep was strongly associated with amyloid burden.”

Yo-El Ju, MD, associate professor of neurology and sleep medicine specialist at Washington University, agreed. The measurement of amyloid burden and AD-related brain changes in cognitively unimpaired adults avoids the confounding factors that have limited other analyses, she said.

Dr. Ju also noted that the cross-sectional design prohibits making causal associations between sleep disturbance and AD. “There could be other variables that account for the increase in amyloid deposition and risk for AD, so until we have good, longitudinal studies in clinically normal populations we won't be able to definitively show a causal association,” she said.

But, she added, the study confirms in a healthy cohort of older adults “a line of thinking that other research groups, including my own research at Washington University, are showing.”

“I was struck by how common obstructive sleep apnea is in this cohort,” Dr. Ju added. “I do think it is important to look for sleep disorders among otherwise healthy older people because they are exceedingly common. Most sleep disorders are undiagnosed, particularly among people who do not have access to a subspecialist, and many people don't realize they have a sleep disorder.”

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“There is an efficient treatment using continuous positive airway pressure (CPAP) and treating SDB may help to reduce the risk of cognitive decline and dementia. It will also improve quality of life.”—DR. GERALDINE RAUCHS

Dr. Zee added that the apparent healthiness of the cohort—reporting no specific sleep disturbance symptoms and excessive daytime sleepiness—lends support to the recommendation for screening asymptomatic older adults.

“In light of the current US Preventive Services Task Force (USPSTF 2017) conclusion that there was insufficient evidence to support screening for sleep apnea in asymptomatic individuals, I think this study provides additional evidence in support for screening at least in an older age group.”

“Clinicians are just beginning to be aware of the relationship between SDB and AD, and specifically of the longitudinal studies showing that SDB as a risk factor,” Dr. Zee said. “I would add that sleep-wake fragmentation associated with other sleep disorders has also been shown to be risk factor for AD and mixed dementia. Older adults should be screened for SDB, particularly those at higher risk—including those with obesity, hypertension, diabetes, cognitive impairment, or history of stroke. There are screening questionnaires and home testing which will facilitate diagnosis and eventual treatment.”

Disclosures

Drs. Rauchs, Ju, and Zee reported no disclosures.

Link Up for More Information

• Andre C, Rehel S, Kuhn E, et al; for the Medit-Ageing Research Group. Association of sleep-disordered breathing with Alzheimer disease biomarkers in community-dwelling older adults. A secondary analysis of a randomized clinical trial https://jamanetwork.com/journals/jamaneurology/article-abstract/2763344. JAMA Neurol 2020; Epub 2020 Mar 23.