4 Questions on the Connection Between Sleep-Disordered Breathing and Alzheimer Disease

 

Sleep-disordered breathing (SDB) may be associated with several biomarkers for Alzheimer disease among community-dwelling older adults, according to a new study published in JAMA Neurology.

According to the authors of the study, these findings support the necessity of screening for and treating SDB to lower Alzheimer disease risk.

They performed a cross-sectional study in which they assessed data from the Age-Well randomized clinical trial of the Medit-Ageing European project in Caen, France. A total of 157 participants were assessed initially. Of these participants, 137 were enrolled in the Age-Well clinical trial, and 127 (mean age 69.1 years) were included in the present study. Eligible participants were required to complete a detailed neuropsychological assessment and undergo magnetic resonance imaging, polysomnography, and florbetapir and fluorodeoxyglucose positron emission tomography scans.

Participants were classified as having SDB or no SDB using an apnea-hypopnea index cutoff of 15 events per hour. SDB parameters included hypoxia severity, sleep fragmentation, or frequency of respiratory disturbances. Both groups were compared voxelwise for each neuroimaging modality. Secondary analyses were performed to identify which SDB parameter was likely associated with the observed brain changes, and to assess whether SDB severity and/or SDB-associated brain changes could be associated with changes in cognition and behavior.

The results of the study indicated that participants with SDB had greater amyloid burden, gray matter volume, perfusion, and metabolism. The researchers noted that these observations overlapped primarily over the posterior cingulate cortex and precuneus. However, they added, no association was observed for cognition, excessive daytime sleepiness symptoms, or self-reported cognitive and sleep difficulties.

“The SDB-associated brain changes in older adults who are cognitively unimpaired include greater amyloid deposition and neuronal activity in Alzheimerdisease-sensitive brain regions, notably the posterior cingulate cortex and precuneus,” the researchers wrote.

Neurology Consultant discussed the implications of these findings further with lead study author Géraldine Rauchs, PhD.

NEURO CON: Could you discuss what your findings add to the current literature in terms of the brain mechanisms underlying the link between sleep-disordered breathing and Alzheimer disease?

Dr Rauchs: Several previous studies have shown that SDB is associated with increased beta-amyloid (Ab) levels in cerebrospinal fluid. The originality of our study relies on the fact that we used different neuroimaging techniques to determine which brain areas are the most sensitive to the effects of sleep apnea, and to reveal the underlying mechanisms. All the changes we reported co-localize in a brain area that is early affected in Alzheimer disease, namely the posterior cingulate cortex and the precuneus. The fact that we observed greater grey matter volume, greater glucose metabolism and perfusion suggests the existence of neuroinflammatory processes. However, this hypothesis needs to be confirmed using specific markers of neuroinflammation.

NEURO CON: Will these findings inform future guidelines on screening for sleep-disordered breathing, especially in older patients who are asymptomatic, to decrease risk of developing Alzheimer disease?

Dr Rauchs: This study clearly emphasizes the relevance of sleep disorders and particularly sleep-disordered breathing and the need to prevent, treat, or decrease the burden of this disease, especially in elderly people. Further works are still needed to better understand the situation in which SDB is most damageable and needs treatment. Thus, it is well acknowledged that the apnea-hypopnea index (AHI) does not perfectly reflect the severity of SDB. Indeed, some patients can have a high AHI (e.g. > 30), indicating severe SDB, but with no or limited symptoms. In contrast, other patients with an AHI at about 20 may experience more severe symptoms.

Several factors may interact and explain the severity of the disease and the presence of symptoms, and we need to identify the most relevant factors to target the specific populations who are at risk. Of note, hypoxia is likely to be one of these factors, and our study shows that it was the strongest predictor of amyloid deposition.

NEURO CON: What key clinical takeaways do you hope neurologists learn from this study?

Dr Rauchs: The main message for neurologists, but also for general practitioners, is related to the relevance of asking how their patients sleep and informing them about the symptoms of sleep apnea. If patients complain of poor sleep and/or daytime sleepiness, it is important to screen them for SDB. Continuous positive airway pressure is an efficient treatment, so SDB is not a fatality. Treating SDB may reduce the risk of cognitive decline and dementia, and it has also been shown that treating SDB reduces the risk of cardiovascular diseases.

NEURO CON: What is the next step for future research in this area?

Dr Rauchs: The next step of this work is to study how these brain alterations will evolve over time among patients who will be treated vs those who will not accept the treatment. We also want to assess how gender may modulate the impact of SDB on the brain.

—Christina Vogt

Reference:
André 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 [Published online March 23, 2020]. JAMA Neurol. doi:10.1001/jamaneurol.2020.0311