Sleep Apneas Show Association With Tau Accumulation in Cognitively Unimpaired

Diego Z. Carvalho, MD, and neurology fellow, Mayo Clinic

Diego Z. Carvalho, MD

In a recent assessment of witnessed apneas during sleep in elderly, cognitively unimpaired patients, investigators identified a notably association between sleep apneas and elevated tau positron emission tomography (PET) signals, suggestive of a possible effect of apneas on tau accumulation.¹

The raised signals were identified by a cross-sectional analysis in the entorhinal cortex, as this region of the brain is highly vulnerable to tau accumulation, with the cerebellum crus as the reference region (standardized uptake value ratio, SUVR). After controlling for several confounders, the model showed an approximate elevation of 0.049 (95% CI, 0.011 to 0.087; P = .012) in the entorhinal cortex tau.

“I was surprised that we could see a change in tau levels at such early stages, meaning elderly participants without any cognitive impairment,” Diego Z. Carvalho, MD, first author, and neurology fellow, Mayo Clinic, told NeurologyLive^®. “The scientific community is interested to see whether [continuous positive airway pressure] treatment can slow down this process. We would like to be part of this endeavor.”

In total, 15% of the total 288 cognitively unimpaired participants (n = 43) had apneas which were self- or informant-reported during sleep. Researchers also found that patients with apneas had a mean 4.5% higher levels of tau in the entorhinal cortex than those who did not have apneas, after controlling for several other factors such as age, sex, education, cardiovascular risk factors, and other sleep complaints.

The study’s limitations included the small sample size and preliminary nature. As well, a lack of confirmation of sleep apneas in sleep studies as well as no knowledge of whether or not patients were receiving treatment for sleep apnea were other limitations. The cohort was originally part of the population-based Mayo Clinic Study of Aging, in which patients ≥65 years of age who had both tau-PET and amyloid-PET scans completed questionnaires exploring them and their bed partners for witnessed apneas.

A poster presentation of these witnessed apneas and their significant association with observed tau in the entorhinal cortex will be presented at the American Academy of Neurology (AAN)’s 2019 annual meeting in Philadelphia, Pennsylvania.

“Screening for sleep disorders should be adopted by primary care providers because sleep is important for our health. Poor sleep, particularly sleep apnea, has been associated with cardiovascular and metabolic disorders, which increase the risk for hypertension, diabetes, and heart disease,” Carvalho explained. “More recent research has shown that sleep disturbance may accelerate brain aging and accumulation of proteins seen in Alzheimer disease—tau and beta-amyloid. We know from longitudinal studies that sleep apnea is associated with cognitive decline and increased risk for dementia, so it is very likely that treating it early may at least postpone the onset or slow down the process of dementia.”

“However, further studies are needed to confirm that sleep-based interventions are efficacious,” he added.

Despite recent evidence suggesting an association between sleep disruption, specifically obstructive sleep apnea (OSA), and an increased risk of developing dementia, the underlying pathological processes at play remain poorly understood. However, the awareness of OSA’s association with neurological conditions has become more widespread. Within the last year, a number of studies have identified OSA’s relationship with stroke symptoms and its role as a potential risk factor for sudden unexpected death in epilepsy (SUDEP).^2,3

One study found a high frequency of probable OSA in those being monitored for epilepsy, who tended to be older and heavier, with higher screening symptoms for sleep apnea, more frequent focal seizures, and a longer epilepsy duration (P <.05 for all).² The other, in stroke, found that starting CPAP therapy for OSA as soon as possible after an ischemic stroke or transient ischemic attack significantly improves neurological symptoms and physical functioning (P = .0237).³

REFERENCES

1. Carvalho DZ, St Louis E, Boeve B, et al. Witnessed apneas during sleep are associated with elevated tau-PET signal in the entorhinal cortex in cognitively unimpaired elderly. Presented at AAN Annual Meeting; Philadelphia, PA; May 4 to 9, 2019. indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-002114.pdf. Accessed April 30, 2019.

2. McCarter AR, Timm PC, Shepard PW, et al. Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy. Epilepsia. 2018;59(9):1-9. doi: 10.1111/epi.14548.

3. Bravata D, Sico J, Vaz Fragoso C, et al. Diagnosing and Treating Sleep Apnea in Patients With Acute Cerebrovascular Disease. J Am Heart Assoc. 2018;7. doi: 10.1161/JAHA.118.008841.